Principles of Evolution, Ecology and Behavior

The lecture presents an overview of evolutionary biology and its two major components, microevolution and macroevolution. The idea of evolution goes back before Darwin, although Darwin thought of natural selection. Evolution is driven by natural selection, the correlation between organism traits and reproductive success, as well as random drift. The history of life goes back approximately 3.7 billion years to a common ancestor, and is marked with key events that affect all life.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 1

Transcript



January 12, 2009



Professor Stephen Stearns: Biological evolution has two big ideas. One of them has to do with how the process occurs, and that's called microevolution. It's evolution going on right now. Evolution is going on in your body right now. You've got about 1013th bacteria in each gram of your feces, and they have enough mutations in them to cover the entire bacterial genome. Every time you flush the toilet, you flush an entire new set of information on bacterial genomes down the toilets. It's going on all the time.



Now, the other major theme is macroevolution. This process of microevolution has created a history, and the history also constrains the process. The process has been going on for 3.8 billion years. It has created a history that had unique events in it, and things happened in that history that now constrain further microevolution going on today.



That's one of the tricky things about evolution. It has many different scales. My wife always gets frustrated with me. She says, "Well when did that happen?" I say, "Oh not too long ago, only about 20 million years." And, you know, that's what happens when you become an evolutionary biologist, you zoom in and out of deep time a lot. And this process of microevolution is going to be the first thing we examine. It's the nuts and bolts. It's what's really created the patterns. But the patterns of macroevolution are also very important because they record the history of life on the planet and they constrain the current process.



So the evolution part of the course is set up basically with two introductory lectures. Then I'm going to spend six lectures talking about microevolutionary principles. So these are things that you can always return to if you are puzzled about a problem. Then there'll be five lectures on how organisms are designed for reproductive success. This includes cool stuff like sexual selection, mate choice, that kind of stuff. I usually manage to give the sexual selection lecture just about on Valentine's Day.



Then we'll do macroevolutionary principles. This has to do both with speciation, how new species form, and with how biologists now analyze the tree of life to try to understand and infer the history of life on the planet. Then we'll take a look at that history, looking at key events--and this includes both fossils and the diversity of organisms--and some abstract organizing principles about life. So all of those are part of how we can analyze the history of life on the planet.



And then, just before Spring Break, we will integrate micro and macroevolution. We'll do it in two different ways. We'll do it with co-evolution, where micro and macro come together, and we'll also do it with evolutionary medicine, where both kinds of thinking are necessary really to understand disease and the design of the human body.



So where did this idea of evolution come from? Well, there are always ideas. You can go back to Aristotle and find elements of evolutionary thought in Aristotle. But really it's a nineteenth century idea, and in order to see how it developed let's go back to about 1790 or 1800; so at the end of the Century of the Enlightenment.



At that point, if you were to ask a well-educated person living in a Western culture how old the world is, they would say, "Oh thousands of years." And if you were to ask them, "Well, where did all these species on the planet come from?" they would say they were all created just the way they look now and they've never changed. And if you asked them, "Have there ever been any species that went extinct?" they would say, "No, everything that was created is still alive and can be found somewhere on the planet."



So when Alexander von Humboldt, who was certainly a creature of The Enlightenment, sets out to explore South America, he thinks that he might encounter some of those strange fossils, that the French have been turning up in the Paris Basin, on top of Tepuis in Venezuela. So he really thought that there was a lost world. Of course, Arthur Conan Doyle later wrote a novel about that. But these guys actually thought, "Hey, I go to Venezuela or I go to the Congo, I might meet a brontosaurus." That was what they thought at that time.



They thought that adaptations were produced by divine intervention. They did not think that there was a natural process that could produce anything that was so exquisitely designed as your eye. We now know that your eye is in fact very badly designed, but it looked pretty good to them. Anybody here know why the eye is badly designed? What's wrong with your eye?



Student: The blind spot.



Professor Stephen Stearns: It's got a blind spot and--?



Student: [Inaudible]



Professor Stephen Stearns: It's got--the nerves and the blood vessels are in front of the retina. The light has to go through the nerves and the blood vessels, to get to the retina. The octopus has a much better eye.



Okay, now by the time that Darwin published his book in 1859, people thought that the world is very, very old; how old they weren't sure. We now know about four-a-half billion, but at that point, based on the rate of erosion of mountains and on the saltiness of the ocean, assuming that the ocean had been accumulating salt continuously, and that it hadn't been getting buried anywhere, which it does, people thought hundreds of millions of years. They weren't yet in the billions range, but they thought hundreds of millions.



They knew that fossils probably represent extinct species. That was Cuvier's contribution. He did it for mammal fossils in the Paris Basin. Geoffrey Saint-Hilaire had had a big debate with Cuvier about homology, and that was in 1830. By the way, it was one that many people throughout Europe followed very closely--this was a very, very key intellectual topic at the time--and it was about homology. Basically it was about the idea that Geoffrey Saint-Hillaire had had that if my hand has five fingers then--and a bat's wing has five fingers and the fin of a porpoise has five fingers--that that indicates that we all got those five fingers from a common ancestor, and therefore we are related because we had a common ancestor.



So you could see that in 1830. That's before Darwin publishes his book. Okay? Then of course we have the idea that adaptations are produced by natural selection; and we owe that to Darwin. And I will run through the process he went through between 1838 and 1859 very briefly. This is one of the most important ideas about the nature of life, and therefore about the human condition, that's ever been published, andI strongly recommend that, if you have a chance, read The Origin of Species. Darwin actually was quite a good writer. It's Victorian prose, so it's a little bit like reading Dickens. But it's good stuff, he has a nice rolling style.



How did he come to it? Well Darwin was a med school dropout. Went to Edinburgh, didn't like med school; loved beetles and became passionate enough as a naturalist to become known, as a 22-year-old young man, as a guy who might be a good fellow to have on an expedition. And the British Admiralty was sending Fitzroy around the world to do nautical charts and Darwin got on the ship.



So at an age not very much greater, or perhaps even a bit younger than some of you, Darwin sets off. He's 22 years old. He wants to know how species form. He has set himself that goal. So he's ambitious. He's set a clear goal. The goal is to solve one of the most pressing problems that biology has at that time: where do species come from?



Now the stimulus that he has is in part from Charles Lyell, the geologist, who had discovered deep time, and that convinced Darwin that there would've been enough time. He stops in Argentina. In the banks of a river in Argentina he can see giant fossil armadillos, and then right on top of that same bank he can see the current armadillos walking around, up on top of the bank. There they are; the live ones are right above the fossil ones. They look the same but--I mean, they look similar--but they're not the same. So there's some connection there.



He gets on a horse in Chile and he rides up into the Andes and he sees marine fossils lifted thousands of feet above sea level; clearly some dynamic process is going on that had lifted those marine fossils up. He doesn't know about continental drift yet--right?--but there the fossils are.



In the harbor at Valparaiso he sees the effects of an earthquake that had happened just before they arrived. It was a big one. It was probably as large as the earthquake that recently caused the big tsunami in Indonesia--so it was probably an 8.5, 8.6 earthquake--and it had caused an uplift in the harbor of maybe 50 feet. So he began to see the world as dynamic. Things hadn't always been the way they are.



Then he goes to the Galapagos, and please navigate the Galapagos website and have a look at some of these differences. The thing that Darwin noticed is that the mockingbirds are different on the different islands. If you go to the Galapagos what you'll notice is that if you land on Espanola, the mockingbirds really want your water supply, and they will hop onto your head or your knee to try to get at your water supply. But, in fact, the mockingbirds all look a little bit different on the different islands, and that's what Darwin noticed.



He could also see that that the marine iguanas look a bit different, and the land iguanas look different. Interestingly, he didn't notice the differences in the finches, until he got back to England and gave his collection to the British Museum, and the ornithologists at the British Museum came in and said, "Hey Darwin, do you realize that the finches on these islands are different?" And that was when he began to really see how many differences could accumulate, how rapidly, when you take a migrant from Central America and put it on an isolated archipelago.



So he goes back to London. He's been onboard ship for about four years. He has a problem with seasickness. He never again sets foot on a ship. He doesn't want to go near the water after being four years on this ship. He had a few issues with the captain too, Fitzroy, but mainly it was that he had a very bad upset stomach onboard the Beagle.



He reads the Reverend Malthus on population growth. Malthus's book had come out in 1798. Malthus said basically that populations grow exponentially but agriculture grows linearly. Therefore populations will always outstrip their resource base. This convinced Darwin that all organisms are in a competitive struggle for resources, and that that must inevitably be the case. He saw very clearly how powerful reproduction is at generating exponential population growth. We will come back to that in the ecology portion of the course.



And we now know that organisms are in competition really essentially not just over food resources, they are in competition over anything that will get their genes into the next generation. So that can be competition for mates. It can be competition for nesting sites, competition for food; lots of different things. But at any rate this primed Darwin's thinking. So he writes down the idea of natural selection. It comes to him in 1838; it's in his notebooks in 1838.



Basically, I'll run through natural selection in a minute. It's a deceptively simple idea because the mechanism looks so simple, but the consequences are so wide ranging. Darwin recognized what the consequences were. And he didn't publish immediately. He did other things. He went off and he worked five or six years on barnacles. He wrote down lots of ideas about things unrelated to natural selection, and he wasn't really jogged out of this until a letter arrived in 1858 from Alfred Russel Wallace, a young British naturalist who had, in a fit of malarial fever, had the same idea, in Indonesia.



And Wallace knew that Darwin had been thinking about these things, and he sent Darwin a letter. And at that point Darwin, British gentleman as he was, had to decide whether he would do the sort of gracious, honorable thing and let Wallace have the idea, or do the honest thing, which, his colleagues knew, was that he had already had the idea. And what they decide upon is that they will do a joint publication.



So if you go to the Biological Journal of the Linnaean Society for 1858, which is in the Yale Library, you can look up the back to back papers by Alfred Russel Wallace and Charles Darwin in which the idea of Natural Selection is laid out. And then Darwin rushes his book into print. So he has been working on a book that was probably going to be about 1200 pages long, and instead he publishes an abstract of it, which he calls "The Origin of Species", which is about 350 pages long. And it sells out on the first day, sold all 6000 copies on the first day, and has remained in print ever since.



That's The Beagle. Darwin slept in a hammock in the captain's cabin, at the back of the ship, which rocked horribly. And that's essentially all I want to do about the development of the idea of Evolution. Basically what I did was I wanted to give you the feeling that there was somebody like you who went out and knew what a deep problem was, and happened to have the luck to get into a special situation where they were stimulated, and came up with an idea that changed the world. No reason it can't happen again.



So now I'm going to give you a brief overview of microevolution and macroevolution. Here's Natural Selection; here's Darwin's idea. If, in a population, there is variation in reproductive success--what does that mean? Would everybody in the room raise their hand if they're an only child? Look around. There are about five or six. How many of you come from families with two children? Lots. How many with three? Quite a few. How many with four? Quite a few, but not as many as there with only children. Anybody with five? Yes, a couple. Anybody with six? No. If we were, by the way, in the nineteenth century, at this point there would still be lots of hands going up.



What you've just seen is the amount of variation in reproductive success represented by the families in this room. Variation in reproductive success basically means that different families have different numbers of offspring, or different individuals have different numbers of offspring. Then there has to be some variation in a trait.



How many of you are under 5'5? Raise your hands. How many between 5'5 and 6 feet? How many over 6 feet? Lots of variation in height in this room. So we got lots of variation in reproductive success; lots of variation in height. There has to be a non-zero correlation between reproductive success and the trait. On this particular trait there's been some research. Turns out that taller men have more children. I don't know whether that's just an NBA effect or what that is but it turns out to be true in many societies.



So there is a non-zero correlation between the reproductive success and the trait. Then there has to be heritability for the trait. The heritability of height in humans is about 80%. So all of the conditions for natural selection on height are present in this room. All you have to do is go out and have kids and it will happen.



So if you're ever in doubt about whether evolution is operating in a population, go back to these basic conditions. You can always decide whether it's likely to be operating or not. We can turn natural selection off by violating any of these four points. If there's no variation in reproductive success--for example, if there is lifetime monogamy and a one-child policy, there will be zero-variation in reproductive success if everybody just has one child; of course some people will still have zero, but that's about as close as you can get.



If there's no variation in the trait--if the trait is like five fingers; there are very few people with six fingers; there are some, but very few. If there's a non-zero correlation between reproductive success and the trait; if there is a zero correlation between reproductive success and the trait. We'll go into all the conditions for that. That results in neutral evolution. Okay? Then things just drift. Well have a whole lecture on that. Or if the trait is not heritable, if there's no genetic component to it, then it won't evolve.



So Natural Selection-I wonder why it's doing that? Sorry- Natural Selection does not necessarily happen. It only happens under certain conditions. Essentially in this picture, this is what I've just told you about Natural Selection. If there's variation in the trait, represented on the X-axis, and there's variation in reproductive success, based on the Y-axis, and there is a correlation between the two, represented by the fact that I can just about draw a straight line between these points, Natural Selection will occur and it will push the trait to the right.



If all of these conditions, except the correlation, occur--so you have variation in the trait, variation in reproductive success but no correlation--then you get random drift. And these two situations result in radically different things. This situation produces adaptation, it produces all of the fantastic biology that you're familiar with. It's produced meiosis; it's produced your eye; it's produced your brain. It's extremely powerful.



This situation on the right, the random drift situation, is what connects microevolution to phylogenetics, and it's what allows us to use variation in DNA sequences to infer history. And I'll get to that. That statement right now is opaque. Don't expect that one to be transparent at this point. But two or three lectures from now I will go into that in detail and you will see that we need to have a process of drift in order to generate a kind of large-scale regularity that gives us timing and relationship in macroevolution.



So both are driven by variation in reproductive success. The difference is in whether there's a correlation between the variation of the gene or the trait and the variation in reproductive success.



If we have strong selection, we can get pretty amazing things. I could illustrate adaptation a lot of different ways. I could do it say with the leaf cutting ants that were the first farmers; they domesticated a fungus 50 million years ago and have been cultivating it ever since. That would be one way I could do it.



I could do it with the exquisite morphology of the deep sea glass sponges and how efficient they are at filtering stuff out of the water. I could do it with the design of a shark's body. Lots of stuff.



I'll do it with bats, in part because when I was a Yale undergrad I worked on bats in this building. We had a guy that did research on bats at that time. Now a lot of bats are insectivores, and they will hunt moths at night, in complete darkness. They do it with sonar.



The bat only weighs about say 50 to 100 grams, and it is making a sound that is as loud as a Metallica concert when you're standing right next to the lead guitar's speaker system. Okay? Or it's as loud, if you like, as a Boeing 747 taking off from a runway. It's this tiny little creature. It's making an incredibly loud sound. It's 130 decibels.



It does that because the intensity of sound, the amplitude of sound, decreases with the square of distance, and it needs to detect an echo coming back from the moth. The echo coming back from the moth--which by the way it can pick up at a distance of about 20 feet--is about a million times less loud, and it's only coming in about one to two milliseconds later. So imagine, there you are, you've gone "woo"--except a lot louder than that--and milliseconds later you hear "click", and you haven't deafened yourself.



That's exquisite. It has all kinds of physiology in its ear to hear the returning echo, and it can actually discern whether or not it's looking at a kind of a fuzzy moth or a smooth beetle. The moth has all kinds of adaptations to try to get away from the bat. It hears the bat. The bat's cruising around, the moth hears the bat. The moth goes into a desperate spiral, diving towards the ground--okay--the bat starts to swoop in. There is a mite that lives in the ear of moths. I think you begin to understand the problem that this mite has. If the moth gets caught, the mite will be eaten.



The mite's solution? It only lives in one ear. If you collect moths and you look for mites in their ears, you will find that they are always only on one side. So the moth always has a clear ear so it can hear the bat. There's stuff like this all through biology.



There's another kind of a bat, called a Noctilio, hunts fish. A Noctilio basically detects ripples in the water surface, and then it swoops down and it gaffs the fish with its hind legs. It can detect a wire 1/10th of a millimeter in diameter, sticking 1/10th of a millimeter above the water surface. When I was taking care of bats, I'd never seen a Noctilio. I thought, "God, this must be the greatest bat in the world."



About four years ago, on the Amazon, my wife and I went out in a canoe, at sunset, on a lake, just off the Amazon River. It was starting to get dark. All day long the kingfishers had been fishing on that lake, and during the day the lake had gotten covered with a lot of food that the fish wanted, but they were afraid of the kingfishers. As it got darker the kingfishers couldn't hunt anymore and the whole surface of the lake dimpled with the fish coming up to eat the food.



So their timing was exquisite. They knew exactly how dark it had to get before they were safe. The fish came up and started to eat the food. At that point--it was just shortly after sunset--the bat falcons were still stationed around the lake. You could see, up on the trees, falcons sitting up on the limbs and making flights off of the limbs. About 15 minutes after the fish started to eat, it got dark enough so that the bat falcons couldn't hunt anymore, and at that point Noctilio came out, and the water was covered with hundreds of bats that were catching the fish. They were catching the fish within a meter of us.



Now there are a couple of things about that story that I think, uh, I'd like to underline. One is that that entire community is exquisitely adapted. Every element in it knows when everything is going on and what the risks are, and what the costs and the benefits are. The other thing is that I had benefited from a liberal education, and when that bat came out, and was flying around a meter away from my canoe in the Amazon, my life was so much richer because I had been waiting to see it for 40 years. I had heard about it in a course at Yale. I knew where it fit in. I knew what kinds of adaptations it had, and boy was I happy to see it.



So adaptation can be impressive. Drift is something that actually appeals to the geeks among us. I have a geeky side too, okay? Drift isn't such a morphologically or artistically beautiful thing. It's a mathematically beautiful thing. Drift happens whenever there is no correlation between reproductive success and variation in a trait, and it produces patterns like this.



So here we start off with 20 populations, and we start them all with a gene frequency of 0.5, and we let meiosis--which is like flipping a fair coin--and we let variation and reproductive success take their course, and we just run these populations for 20 generations, and you can see that there's just about an equally likely distribution of end-states out here. So we all start off at 0.5, and it gets noisy as we go along.



So this is an image of the process of drift, and if any of these populations happens to get up to 1, or down to 0, in terms of gene frequency, the process will stop, because those are absorbing states. If the frequency becomes 1, then everybody's got it and there can't be any change, and if the frequency becomes 0, then nobody's got it and there can't be any change. So that's what's meant by absorbing state.



Now to a first approximation, whole organism traits are the products of Natural Selection. Maybe not in the immediate past, but usually at some point in the history of life, a whole organism trait will have been under Natural Selection. So it will have been shaped and designed by this process. And to a first approximation, a lot of DNA sequences have been shaped by drift. So we see design in the whole organism and we see noise in the genome--to a rough cut; lots of exceptions.



There are DNA sequences that have clear selective value; in fact, there's a whole literature on this now. If any of you want to write an essay on signatures of selection in the genome, you can find lots of stuff on that now, on how to recognize that a chunk of genome has recently been under selection. There are whole organism traits that have no apparent selective value; for example, the chin.



The chin actually is the result of evolution, operating on development, to take a face, which is like that of a gorilla or a chimpanzee, which bulged out like this and essentially flattened it out; so that we are vertically much flatter than a chimp or a gorilla, and as a result of this being pushed back, something that was there, but kind of covered up, stuck out.



So that's where the chin came from. That doesn't mean chins were selective. Now it may be that after they originated, that there could've been a little bit of sexual selection operating on them. But certainly the developmental process that originally produced them didn't have to be adaptive. It could just be a byproduct of something that was going on, basically from the mouth up.



So the themes of microevolution are selection and drift. Natural selection is driven by variation in reproductive success. The strength of selection is measured by the correlation of variation in a trait with reproductive success. When there's no correlation, there's no systematic change, and then things just drift, okay?



Now macroevolution; the big scale process, the big picture. Well here are sort of the basic statements about macroevolution. If anybody asks you, "What does this fancy word macroevolution mean?", tell them basically this is it. There's one tree of life. Everything on the planet had a common origin. Everything is related to everything else, with the possible exception of the viruses, which are too small for us to decide; their genomes are too small. The branch points in the tree, speciation events--that's when new species were formed.



This history is marked by striking major events. There have been mass extinctions. There have been meteorite impacts. There have been major changes in the organization of the information structure of life. And the biological disciplines that you may encounter map onto this timeline. So actually different parts of biology study different parts of this process.



The tree looks like this. This is the large-scale tree. So at this scale, what you see here are the three kingdoms of life, which are the bacteria, the archaea, and the eukaryotes, up here; the root's at about 3.7 billion years, not million years. And at one point a purple bacterium got into the eukaryotes and became a mitochondrion, and at another point a cyanobacterium got into various plant lineages, three times, and became a chloroplast.



So that's the large scale. And you're probably searching around on that to find out where you, the most important thing in the universe are, and you're way up here, on a little twig. Okay? Now if we blow that up and just look at the multi-cellular organisms, multi-cellularity looks like it originated around 800 million to a billion years ago. And these are the fungi, these are the things we call the plants, multi-cellular plants, and then off in this direction we have got a fairly complicated series of branches that end up with us being up here. Okay?



The things that are--this was done by Tom Pollard, at MCDB, about five years ago, and at that point the things in yellow had genomes that had been completely sequenced. Now there are hundreds of completely sequenced genomes. So for the first two billion years of life most of the action is down in the basal radiation. So going on with bacteria, archaea and eukaryote ancestor; single-celled things. At that scale--we're just way up at a small twig on the tip--and symbiotic events brought mitochondria and chloroplasts into eukaryotic cells.



Already this is telling you something interesting about yourself. You are a community of genomes. You are not a unitary genome. You've got that mitochondria in you. The main themes are basically that the speciation events that have occurred, particularly over the last billion years or so, have created a tree of life that describes the relationships of everything on the planet.



Systematic biology, phylogenetics, tries to infer the history of life by studying those relationships. And there's a real deep issue here of how do we infer the tree? The tree--organisms don't come with a barcode on their foreheads telling us who they are related to. We have to try to figure out who they're related to, and when we understand the relationships, then we know the history, because the relationships define the history.



So we work with hypotheses about history, and we test these hypotheses against each other and try to come up with the one that's most consistent with the data that we've got. And they give us a historical framework within which we can then interpret what's happened. There are major events that have happened. Briefly these are they.



Life originates about 3.6 to 3.9 billion years ago. And, by the way, it seems to have originated fairly quickly. Within probably about 100 million years--see I'm being an evolutionary biologist again--within just a hundred million years, uh, after water could exist on the surface of the planet in liquid form--so following the meteorite bombardment, when the surface of the planet cools down enough for water to be liquid--life probably originates pretty quickly. And arguably, within the first hundred generations, the first parasites were around. So those things happened pretty quickly.



Then eukaryotes and meiosis, which is how a biologist refers to organized sex, happened about 1.5 to 2.5 billion years ago; multi-cellularity, which gives us developmental biology, about a billion years ago. All the major body plans for animals appear to have, with the exception perhaps of the, uh, jellyfish and a few of their relatives, they all seem to have originated about 550 million years ago.



There was a near loss of life on the planet in the Permian mass extinction. We will study that later in the course. You're welcome to write an essay on mass extinctions if you want to; you know, big death is kind of exciting. It seems to have occurred basically by a process of poisoning of the oceans. The flowers radiate about between 65 and 135 million years ago.



Language is important because once language occurs, then we have an independent kind of information transmission from generation to generation; we get cultural transmission. That's probably about 60-100,000 years old; at least with syntax and complicated information storage. Writing is only about 6000 years old. And of course the important stuff is quite recent.



So this is a view of life that goes from bacteria to dinosaurs to rock and roll; and that all can be studied with evolutionary principles. How do the biological disciplines map onto this? Well microbiology and biochemistry try to study things that are common to all life. That means that the same chemical reactions that go on in bacteria go on in the human liver, and that's about one-and-a-half to four billion years old. Okay?



Genetics and cell biology study stuff that follows the evolutionary invention of meiosis; to a large degree. There is bacterial genetics, but eukaryotic genetics is something which is studying things that are about 1.5 billion years old. Developmental biology and general physiology, those are multi-cellular disciplines; they depend upon the existence of a multi-cellular organism. That thing didn't come along until about a billion years ago. Neurobiology, you need a complex--you need cephalization--you need to have a complex nervous system. That studies phenomena that are probably about 500 to 600 million years old. Same for behavior.



There are several anthropologists in the class. You guys are studying things that probably originated along our branch of the tree, within the last 15 to 20 million years. So there is a temporal assembly of biology, as a discipline, as well as there is of life, on the planet.



So the key concepts from this lecture are that there are two kinds of explanation in biology. One is the proximate or mechanical question, which is answered by studying how molecules and larger structures work. Those are basically physical and chemical explanations. And then there are the evolutionary questions, which is why does the thing exist; why did it get designed this way? And that could be answered either through selection or through history; or the best way to do it is to use both and combine those explanations.



The thing that distinguishes biology from physics and chemistry is Natural Selection. This is not a principle that you can find in a physics textbook or in a chemistry textbook. This is something that is a general principle that actually applies to lots of things besides biology, but it's not contained within physics and chemistry. And there is a pattern in biology that unites biology with geology and astronomy, and that's history. So there is an important element of historical thought in evolutionary biology, as well as the more abstract action of natural selection on designing organisms for reproductive success and shaping changes and gene frequencies.



Now I want to end the lecture by telling you something astonishing. I won't always be able to tell you something astonishing in every lecture. But one of the great privileges of teaching Introductory Biology, or being in an Intro Bio class, is that there are certain big things that never get discussed again. Okay? This is one of them. We are continuous with non-life.



Here's how I'm going to convince you of that. Think of your mother. Now think of her mother. Now think of your mother's mother's mother. Now I want you to go through a process like you've done in math where you do an inductive proof; you just go back. Just let that process go. Okay? Back you go in time. Speed it up now. Okay? We're back at ten million. Now we're at a hundred million. Now we're at a billion years. Now we're at 3.9 billion years. Every step of the way there has been a parent. 3.9 billion years ago something extremely interesting happens. You pass through the origin of life, and there's no parent anymore. At that point you are connected to abiotic matter.



Now this means that not only does the tree of life connect you to all the living things on the planet, but the origin of life connects you to the entire universe. That's a deep thought. Every element in your body, which is heavier than iron, and you need a number of them, was synthesized in a nova, uh, supernova. The planet that you're sitting on is a secondary recycling of supernova material, and your bodies are constructed of that stuff and they use it in some of their most important processes.



So the vision that evolutionary biology gives you is not only the practical one of how to think about and analyze how and why questions in biology, it's also a more general statement about the human condition, and I hope it's one that you'll have time to reflect on. Next time we'll do basic genetics.



[end of transcript]

Genetic transmission is the mechanism that drives evolution. DNA encodes all the information necessary to make an organism. Every organism's DNA is made of the same basic parts, arranged in different orders. DNA is divided into chromosomes, or groups of genes, which code for proteins. Asexually reproducing organisms reproduce using mitosis, while sexually reproducing organisms reproduce using meiosis. Both these mechanisms involve duplication of DNA, which then gets passed to offspring. RNA is a key component in the duplication of DNA.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, Appendix

Transcript



January 14, 2009



Professor Stephen Stearns: Okay, I'm going to start with an example. Isn't that a great shot of the baby? I mean, the Web is so great. You can download pictures from the Web that just look fantastic.



So I want to start by posing you a problem. Jill and John are going to have a baby, and Jill's got blue eyes and John's got brown eyes. Okay? All of the other men whom Jill knows have blue eyes. The baby has blue eyes. [Laughter] Should John be worried? John's got brown eyes, the baby's got blue eyes, should John be worried?



Well, we can assume that brown eyes are dominant to blue, which roughly speaking is correct. The actual situation is a bit more complex. In fact, if you want to write a paper on the evolution of eye color and the genetics of eye color, there's a lot out there. But this is approximately correct. And John comes from an island where one percent of the people have blue eyes. So that, just on the face of it, would indicate that maybe John ought to be worried.



But in fact just exactly how worried should he be; just based on genetics, not based on behavior or rumors or anything like that? Well we'll come back to that. I do that at the beginning just to point out that there are interesting issues here, and that they are things that touch our daily lives.



So now I'm going to run through, as much as I can, genetics, in the next forty minutes. And please speed me up or slow me down, as you wish, and don't hesitate to interrupt. Some of this may already be very familiar to you. So the genetic material is deoxyribose nucleic acid. We have known that since 1945, and we've known its structure since 1953. And this is actually an extremely important point: Genes are solid particles that are transmitted from parent to offspring. They are not fluid. They're actually material stuff. Okay?



And we know exactly what it is. They encode information, as sequences of nucleotides, and in the DNA it's adenine, thymine, guanine and cytosine. So you can think of those as four letters. They string into a linear chain to form a molecule, and these, uh, there are two strands that are twisted around each other to form a double helix. So it looks like that. The sugar phosphate strands form the backbone, and then the nucleotides are glued onto the backbone and they form pairs; so adenine pairs with thymine, and guanine pairs with cytosine.



The sugar phosphate backbone is the same in every DNA molecule on the planet, and the information in the molecule is in the sequence of nucleotides. You can think of that as letters forming words. So these are big molecules. If you were to put all the chromosomes in your nuclei together, and just for one cell, and string them together, one haploid copy is exactly one meter long. So when they say it is a macromolecule, it is a serious macromolecule. It is a big thing. So just chop this piece of measuring tape up into 26 pieces and you get about the size that you've got in each of your chromosomes. Okay?



When I first isolated DNA from sugarcane, and condensed it in ethanol, it came out, in the ethanol mixture, as a bunch of white, stringy strands, and I could wrap it around a glass rod. This is big stuff. So we're not talking about tiny, weensy, little molecules. DNA is a biggie, and it's very stable.



Now, how does this relate to organisms? Well that's the issue of genotypes and phenotypes, and that's a question of information and matter. So there's a general principle here that's quite intriguing and it has to do with how you turn information into matter. The genotype is basically the info in the DNA, and every cell in your body has got all the information in it that is needed to build a whole organism.



That, by the way, is an interesting statement, because if we can overcome some of the genetic programming of the oocyte, of the egg, we could, in principle, simply put a cotton swab into your cheek and take one cell off of your cheek and then do fancy reproductive medicine and clone you, off of just the DNA in a cheek cell. Now it turns out that the developmental machinery in the egg is really critical, and it's hard to do that. But just from the point of view of the information, any cell in your body could be used to make another you. I can pull out a hair cell, take a cell off of the root of the hair, do the same thing.



The phenotype--basically you should think of that as you. Okay? That's the material organism. It's built according to genotypic instructions. So the genotype contains information, the phenotype contains matter, and the transformation from information into matter is done by developmental biology. Decoding that transformation is one of the major research agendas for the twenty-first century in biology. It's called the construction of the genotype/phenotype map. That's kind of modern jargon for developmental biology.



So where does the DNA actually sit in the cell? Well here's some more vocabulary. I'm building vocabulary for those of you who haven't been in biology recently. I'm going to say a few words here. The eukaryotes, the things that have a real nucleus--which includes us and all other multi-cellular organisms, plus a whole bunch of single-celled ones--they have cells that have a nucleus and the DNA in the nucleus is contained in chromosomes, and these chromosomes are a long structure that has kind of a central scaffold, it's got a central mirror. That's labeled 2 here, on the slide. And the DNA itself is actually wrapped around proteins in the chromosome.



In the prokaryotes, which are the things that lived on this planet for about the first two billion years of life--that is, bacteria and archaea--they are single-celled organisms, and their DNA is basically not in separate chromosomes, but all in one circular loop. So it's a circular chromosome; it's attached to the cell wall. So there's a big difference in the way that eukaryotes and prokaryotes are organized, and in fact the eukaryotic nucleus is very probably the evolutionary residue of a prokaryote; that's where that organelle probably came from. Anybody know what the other organelles are, that used to be independent organisms?



Student: Mitochondrion.



Professor Stephen Stearns: A mitochondrion is one.



Student: Chloroplast.



Professor Stephen Stearns: Chloroplast is another.



Student: Lysosomes.



Professor Stephen Stearns: Not isotopes. Well, maybe lysosomes. There's a little bit better evidence though for another one. Spindle apparatus; the spindle apparatus that pulls the chromosomes apart has a little circular genome associated with it.



Okay, a bit more on chromosomes. The number of chromosomes is usually constant, within a species, although there is some variation. You get 23 from your mom and 23 from your dad. So you've got 46 sitting in every cell of your body, except your red blood cells which don't have a nucleus. That dual set, one from mom and one from dad, together it's called the diploid condition. Okay? So d-i--2; from Greek, diploid.



And in contrast to that, your eggs and your sperm are haploid. So the gametes are haploid. They have one set. Haploid means one set of chromosomes. So the haploid number in humans is 23. The diploid number is 46. World record for a eukaryotic minimum chromosome number is 1. Ascaris, a nematode that lives in the gut of dogs, has 1 chromosome. World record for maximum number of chromosomes? Actually it's probably also in ascaris, but in the somatic condition. That one chromosome falls into about 1000 pieces when it develops. So chromosome number varies widely.



They've got genes and other things in them. You can think of a chromosome as being about 1000 genes, and you can think of a gene as having several thousand nucleotides in it. And you can think of a gene as being a segment of DNA that tells a cell to make a particular protein, a particular structural RNA, and through splicing and other things there are various other classes of RNA that are now important; regulatory RNAs.



You're made out of proteins and materials whose construction is basically governed by the actions of proteins. And so the DNA in your genome is a set of instructions on how to make what kinds of proteins at certain places and times to control the construction of the organism and determine the uniqueness of the species. This, uh, you know, in a few words, describes something which is incredibly complicated and beautiful.



And if you think about how complicated your eyes or your brains or your livers or whatever else is, and you think about that for all of the ten to a hundred million species of organisms on earth, the amount of information stored in the genomes of the organisms on earth is just absolutely astounding. And by the way, when one goes extinct, it's kind of like burning the library at Alexandria, and we lose all of that information.



Okay, genes are in specific locations and they come in different forms. So again, this is vocabulary building. We call the place that a gene is found on a chromosome its locus; this is in classical genetics. And genes can be found in different versions. We call those different versions alleles. So, for example, the gene for eye color is either blue or brown. Those would be the allele for blue or the allele for brown.



If you are carrying two different versions of the gene--you got one from your mom and you got one from your dad and they're different--then you're a heterozygote, and we call that condition the heterozygous condition. If you got the same one from both parents, then you're a homozygote, and we call that the homozygous condition.



What does a gene look like? Well there's a lot now that's known about this, and as a matter of fact I encourage you to do things like go on the Web and just type gene structure, and have a look at all the diagrams that pop up. Normally a gene has got a codon--that is, three nucleic acids--that say, "This is where you're going to start reading me off."



And then it's got another one down at the end that's a stop codon, that says "That's where you stop." And then in between that you've got a long string of DNA--this is in eukaryotes, not in prokaryotes--a long string of DNA, and some of it is going to end up coding for protein and some of it is not. So the part that will code for protein we call the exons; the part that is going to be cut out and spliced and put into messenger RNA, to go out and make protein. And the part that is not we call introns. So not all the DNA is going to go out and become protein.



The central dogma of molecular biology, basically, is that DNA makes RNA makes protein. And transcription is copying the DNA into messenger RNA, and that's done with complementary pairing, and in the process, the thymine is replaced by uracil in the messenger RNA. The introns are cut out and discarded. The exons are spliced together and the RNA is then translated into protein in the ribosome.



There's a lot of activity here for RNA. RNA is doing a lot of stuff, and in fact it's because of the amount of engagement of RNA in this very, very basic process of life that we think that RNA was probably the original genetic molecule, and that DNA evolved after RNA, and then all of this process developed after that. The reason for that is that RNA has a very high mutation rate; DNA has a low mutation rate. But RNA can be an enzyme and DNA is not. So RNA was a--both an information storage molecule and an enzyme, at the beginning, close to the beginning, of life, and then DNA came along later.



So this is a picture of the structure of genes and the process that goes on when the DNA is transcribed into RNA. The RNA is spliced and assembled into a molecule that is then going to code for a polypeptide; or a big polypeptide is a protein. And that will then go through a ribosome to make protein. So the messenger RNA--and by the way, heh, when I was sitting in this room in 1965, I was taught about messenger RNA and the faculty would laugh and they would say, "Nobody's ever seen one."



That was forty years ago. Now they are the basis of high-tech genechips, and people work with them all the time. But that's--you know--this kind of ghost in the machine, from forty years ago, became very concrete by about twenty-five years ago.



Transfer RNA is a much smaller molecule. Transfer RNA, if you think of messenger RNA as being that big, transfer RNA is about that big. And it is the molecule that matches the genetic code, that's sitting there in the messenger RNA, to a particular amino acid. So you can think of--say if this is the messenger RNA sitting here, the transfer RNA is coming along and sitting down on the messenger RNA and matching the code on it, and then on its other end it's carrying--like right here, where I'm wiggling my finger--it's carrying an amino acid. And this whole process will get fed through a ribosome, and out at this end of it the amino acids will get joined together. So the RNA will go out one part of the ribosome, and out of another part will come the growing chain of the protein.



So the transfer RNA is actually the translation device--it is what implements the genetic code--which comes in units called codons. So it takes three nucleotides to specify one amino acid. And you can think of it like this. The DNA is a codon sequence. It gets translated into an RNA, and then in units of three--okay, so in chunks of three nucleotides, the RNA gets translated into protein.



Just to repeat this message, RNA is playing a big role in this whole process, and there's good reason to suspect that it was the original genetic macromolecule. There's an interesting implication in this, and I will not shy away from telling stories like this during the course. Information is flowing out from the genotype into the phenotype. It doesn't go in the other direction. That's very important, that it doesn't go in the other direction. Okay?



This is a re-statement of something that August Weismann said in the nineteenth century. He said that there is a distinction between the genotype--the germline, which is the genotype--and the soma, which we now call the phenotype. And Weismann basically said in the 1880s that information flows from the genes out into the organism and not back in the other direction.



Now the implication of that is that evolution of acquired characteristics won't work. In other words, if during my lifespan I acquire a healthy tan, my child will not inherit it because the information on tanning isn't going to go back into my genome and get transmitted to my kids. If I develop calluses on my feet, they will not be transmitted. If a giraffe stretches its neck on the savanna to try to get to the top of the tree, and thereby actually does physically lengthen its neck by a couple of centimeters, that will not get transmitted to the next generation. Okay?



So that would be evolution of acquired characteristics--characteristics acquired during the lifetime of the parent--and it doesn't work; that's not how evolution works. You're probably sitting there wondering, well how does it work? Hey, that's what this course is about; you're going to find out, don't worry.



Now there was a guy named Trofim Lysenko, who was a demagogue and a corrupt guy; a pretty evil man. He claimed that evolution by acquired characteristics would work, and it would work very rapidly. This would allow crop selection to go on in a period of one generation, rather than ten or a hundred generations, and that therefore in Russia Stalin would be able to move people into Siberia and into areas where crops were not currently grown; and Lysenko said, "And we can guarantee you, scientifically, that these crops will work."



The science was wrong and millions of people died, because they starved to death. Communist China was influenced by Stalin, and in fact Mao bought this stuff for awhile and carried out some similar policies during the Great Leap Forward, in the 1950s, and millions of people starved to death in China as well. The Chinese found it a little bit easier to get rid of this incorrect, this bad science, because after all it was a Russian import. Right? So you could throw it out a bit more easily than the Russians could.



Lysenko, in fact, persisted for quite a while in Russia, and when he was denounced by geneticists who told--were trying to tell Stalin that it was bad science, Lysenko arranged to have them killed; and they were killed, they were executed. Vavilov died in the gulag in 1943; one of the greatest evolutionary geneticists of the twentieth century.



So the point of this is that there's some important stuff about genetics, and it's not just abstract. It's affected science policy, it's affected international relationships, and it's affected the ability of agricultural practices to support human populations. Ideas have very important consequences, and this is just one of the first that you're going to run into, in this course.



Okay, back to genetics. Whoosh. When the cells divide, the DNA replicates and each daughter cell gets a complete copy. This is how inheritance works. Okay? This is why you look like your parents. During replication the ends of the DNA strand are loosened and opened up so that in the notch between the two strands the nucleotides can be inserted. And all of this is done with complex enzymatic machinery and it's done extremely precisely.



Only one mistake in about a billion nucleotides occurs in DNA. It's almost impossible for humans to construct a system that has that degree of reliability. Obviously this precision has been an extremely important thing. Natural selection has worked very hard to get those enzymes that precise. When a mistake does occur, that is one source of mutation. And, in fact, the more frequently DNA is copied, the higher the mutation rate. So that's one place where mutations come from.



When this is going on, this copying is going on in the process of the development of, uh, a multi-cellular eukaryote, like yourselves, or when it's going on in an asexual, uh, eukaryote, basically what happens is the chromosomes go through the process of mitosis. And in mitosis what--what's going on is that the chromosomes will be duplicated, they will line up at a plate, at the center of the cell; spindles will form. So these are proteins, these react in the fibrils here, and they are anchored to an organizing center, which is at the poles of the cell, and they attach to the centromeres of the chromosomes, and they pull one copy into each cell, and then the cell splits.



So that's physically how the copying occurs at the DNA level and then at the chromosomal level, in the cell. And the picture basically is a stained mitosis caught in an onion root tip cell; which is sort of the classical place to observe this.



The important result of this is that if you've got two genes, A and a, that are alleles at the same locus, the two versions of the gene at the same place on the chromosome, mitosis basically consists of a doubling--of first a doubling of the chromosome, so you have enough copies to end up with. They line up at the middle of the cell, and then the spindle apparatus pulls one copy of the A and one copy of the a--in this slide they're on different chromosomes--into each of the daughter cells.



What about meiosis? Meiosis is the process that produces gametes. So it takes the diploid parent down into a haploid gamete. So it's a reduction division. The process is more complicated, and in fact it is like sticking two mitoses together in a sequence, but with a bit of additional machinery.



So the first thing that happens is that the chromosomes are duplicated and they are then actually duplicated again. Then out of, uh, out of the original chromosome there are two--out of the original cell. You're going to go through a process first of duplication, another duplication, and you're going to reduce them each twice by going through two mitoses in, uh, in sequence. And as a result of that, each haploid gamete is getting one original chromosome, or the other, but not both.



That's a cartoon of meiosis. Meiosis is actually much more complicated than that, and is much more precise than I'm able to indicate with these kinds of stick diagrams. But for today's purposes the main thing to remember about it is that meiosis takes a diploid parent and from the diploid parent generates haploid gametes, and each haploid gamete is getting one original chromosome, or the other, but it doesn't get both.



There's a great paper that was written back in 1907 by a geneticist on this issue: Does the behavior of chromosomes explain Mendel's Laws? And it does. So Mendel's First Law is that if you have two alleles, two members of a gene pair, when they segregate into the gametes, one goes into each gamete; that's Mendel's Law of Segregation. So half of the gametes from a heterozygous Aa, will carry the A allele, and half of them will have a little a allele.



So this is the law that allows us to predict what the genotype ratio should be in the offspring, and that allows us to notice any deviations from that genotype ratio. So I'm jumping ahead a little bit here to Punnett diagrams. Just make a note in your head that this fact of segregation is the basis for our being able to predict what the offspring will be like if we know what the parents are like; at least it's part of it.



So if you have two heterozygotes who are mating with each other--so the male gametes have either A or a, and the female gametes have either A or a, it is Mendel's Law of Segregation which tells us that we can expect those gametes to be equally likely. The probability is 50% in each case. When they then come together to make a zygote that's going to grow up to be the offspring, then these--we just multiply these probabilities together. So .5 times .5 gives us .25, and each of these kinds of zygotes is equally likely; 25%.



However there was a reason that we wrote A and a. If A is dominant, that is say it's brown eyes, and a is recessive, say it's blue eyes--and remember our baby with issues--then the ratio here is 3:1. That's only true because--it's 3:1 because in these three cases we have a A, and in this one case we don't. So the ratio is 3:1.



It was this observation of 3:1 ratios in the offspring of heterozygote crosses that caused Mendel to postulate the idea that hey, some genes are dominant and some genes are recessive. If a gene's dominant, you can see that fact in the phenotype; you can see that the allele is present in the phenotype. If it's recessive, you can't see the presence of the gene in the heterozygote. Its presence is covered up by the dominant one.



Mendel's Second Law: What happens when we're looking at two genes and they're on different chromosomes? Well Mendel's Second Law basically says that the events that occur at the different chromosomes are independent of each other. So genes that are sitting on one chromosome are going to be assorting independently to genes that are sitting on other chromosomes.



So in this picture you can see that if we have Aa--and this would be a Aa heterozygote; this is a Bb heterozygote. They are depicted as already having been copied. Okay? So they've been duplicated so that they can start going through the process of meiosis. And what's going to happen is that we're going to pull them apart.



We're going to make four gametes out of each of the chromosomes. This combination, where you get AB and ab, is just as likely as this combination, where you get Ab and aB. Okay? So that's tracking what happens when you have genes on two different chromosomes that are forming gametes. That's Mendel's Second Law.



So meiosis is capable of producing genotypes that are different from the parental genotype. I'll pause for a moment there--I'm not just going to keep running through this slide--because I want to tell you that this is the essence of sexual reproduction. The fact that the offspring gene--genotypes are different from the parental genotypes is the essential evolutionary fact about sex.



It can be achieved in a lot of different ways, but it means that sex produces offspring that are not copies of the parent; they are all different from the parent. And there are two genetic mechanisms that do it. I just showed you the first one. If you've got the genes on different chromosomes, they assort independently. If they're on the same gene--chromosome, you can have crossing over. Okay? So crossing over means that chromosome parts are exchanged during meiosis, and it produces new combinations. Like this.



It's easiest to show you just with a diagram, rather than with words. So when we've made the copies of the chromosomes and they are lined up--I think this is in Prophase 1, if I've got my phases right in meiosis--it is possible that there will be a break and then a rejoining at a certain spot, and this will be done where the DNA sequences are very similar. So the chromosomes can break and be rejoined, and the product of that is gametes that are different. These are recombinant gametes generated by crossing over.



These combinations, this kind of genetic variation, is something that's going on in every generation. The estimate for the human genome is that actually in order to go through meiosis, there must be a crossing-over event, and it is thought that every human chromosome experiences one crossing-over event every generation, roughly; probably true for most organisms. So these things are continually being shuffled.



And the point of that is that there are two mechanisms of recombination. Remember this. Okay? When we say that the genes recombine, they do it both because the chromosomes get shuffled, and because there is crossing over. The crossing over generates new combinations within chromosomes and the chromosome assortment generates new combinations within the genome; both things are going on.



Now mutations are also going on in every generation, and they produce changes in DNA sequences. Some of them make genes that are functional. Some mutated genes have improved. Many don't, many have worse function. A lot of them are neutral. And it's mutations that occur in the germline--that is, in the cells that will form eggs and sperm--that get transmitted to offspring. They have evolutionary significance. So they change the information that's transmitted over evolutionary time.



Mutations that occur in somatic cells are things that lead to cancer. Cancer is a mutational process, and every cancer is a little evolutionary process that occurs just within the lifetime of the person who has it.



Ultimately, if you go back, through the history of life, mutations are where all genetic variation came from. So it's important to understand basically what's going on here. We refer, on the one hand, to point mutations. That's where you just change one nucleotide, and there's a category--there are categories of point mutations. You can have substitutions, you can have deletions, and you can have--a deletion of an entire codon will not cause a change in the downstream amino acids.



So if you take out three nucleotides at once, there won't be any change in the coding for the remaining amino acids. But if you take out one or two, you're shifting the reading frame. So if you have a deletion of one nucleotide or two nucleotides, it changes everything downstream, from that point. So one or two deletions can have really big effects on the information content of the whole genome. We call those frameshift mutations.



Mutations also occur at higher levels. You can have chromosomal mutations where you delete entire genes. So if I say we delete B, I want you to think now that we're taking out maybe 3000 nucleotides. The whole gene disappears; everything from the start codon to the stop codon. We can duplicate a gene, so we get two copies, or we can invert them.



These are very important evolutionary processes. If you duplicate a gene, you can use the old copy to keep things working while you innovate with a new copy. So gene duplications are really important. Your genome has been completely duplicated twice. We can see that in the HOX genes; you'll see that in a few lectures. But in the course of vertebra evolution, once back about with the hagfishes, in the Agnatha, and then once between the Agnatha and the higher fishes, the entire genome was duplicated, and it is thought that this duplication of information may very well have been associated with the fact that there was radiation and a generation of a lot of morphological complexities, because we had duplicated the entire library. You could keep one of them going, to keep everything running, and you could use the other one for innovation. So duplications are important.



Now, to get back to John, Jill, and the baby with issues. Remember I said that John came from an island where the population had a 1% gene frequency. Well we need to think about the whole population then.



Now I want you to think about an out-crossing, sexual diploid population that produces haploid gametes--it could be the population of Connecticut, it could be the population of New Haven, the population of Pitcairn Island--and focus on one gene that occurs as two alleles. Okay? We'll call them A and a.



We've got Mendel's Laws going on. So we have random fair assort--assortment of alleles into gametes, we have random fusion of gametes into zygotes, and we can put that into a Punnett diagram. So this would be for heterozygotes, Aa, mating with Aa. If we look at it as a population diagram, then the frequencies can be anything. It doesn't have to be heterozygote frequencies. We can just say if there's random mating of individuals in this population; some of them are homozygote, some of them are heterozygotes.



We have a population of eggs and a population of sperm, and the frequency of A we will call p, and the frequency of a we'll call q. And it's important to remember--and this is a place where people just getting into it often get fouled up--p and q can be anything between 0 and 1. They're not 50%. Okay? They can be anything between 0 and 1. These genes can occur at arbitrary different frequencies; in the general case.



Well p plus q has got to equal 1, because we only have two possibilities; and that's just the definition of frequencies. The frequencies of the kinds of zygotes they will form are p2, 2pq and q2, and those frequencies also add up to 1. The assumptions behind those statements are that meiosis is fair--so it's just like flipping a coin, it's 50% probability whether you'll get one or the other allele in any particular mating--that mating is random, that there are large populations, and that there's no selection and there's no migration.



So this is kind of an ideal Gas Law for biology, and such laws are very useful in physics and chemistry, and this one is particularly useful in evolution. It tells us that if these assumptions hold, then in every generation you can expect those proportions of genotypes; no mutation.



Well what does it mean? It means that if you start in one generation with frequencies p and q, and you go through that kind of mating, you get zygotes with these frequencies, and in the next generation you get the same gamete frequencies; nothing changes. It's kind of funny that you would place a lot of emphasis on a law that says that nothing changes. But in fact it's extremely important, because it means that, at the level of a population, genetic information doesn't disappear. Gene frequencies stay the same, and that means that the population gets replicated, the whole population gets replicated.



That allows information to accumulate. If this were not true, then the information that had been accumulated would get eroded by just the basic process of genetics. It turns out that genetics and random mating, and, uh, the whole structure of the Hardy-Weinberg assumptions, is set up in such a way that information is preserved at the level of the population. That makes evolution possible. If we didn't have that retention of information, then you couldn't tweak it; it would get eroded by processes other than natural selection.



So it's kind of an inheritance mechanism at the whole population level. And, by the way, it minimizes conflicts among genes about who gets into the next generation. And genetic conflict will be something that we examine in more detail later on; particularly interesting in the context of evolutionary medicine and reproductive biology.



Okay, let's go back to our problem. Jill and John have this baby, and the baby is at issue. So Jill's got--Jill is a--I'm now going to use the words, to drive them home--Jill is a recessive homozygote. She's got two copies of a. John could be either a dominant homozygote, or he could be a heterozygote; he's got brown eyes. The baby's got blue eyes, and is a recessive homozygote. Should John be worried?



Well here's the hint. This is the one new piece of information I'm going to give you. We're going to assume that John's genotype is a random sample of those on the island, and therefore that q2--that's the frequency of aa--is 0.01. So if q2 is 0.01, what is q? .1. Right; 10% probability. What's the probability that John is a heterozygote? This requires having picked up information very rapidly. It's 2pq. Okay? Those are the heterozygotes. The probability that John is a dominant homozygote is p2; p is .9; p2 is .81; 81% probability that John is a homozygote.



Should John be worried; I mean, just on genetic grounds, heh? The only way that that baby could be John's child is if he is a heterozygote. 2pq is 18%; p2 is 81%. Okay? So I did that just to give you a problem that has a little bit of human content to it, that is answered by genetics and by the concepts that we were playing with today. Yes?



Student: The 81%, does that just mean it's not, there's no way, or there's a high probability that there's no way?



Professor Stephen Stearns: Well if he, in fact, is a homozygote, there is no way that that child is his, unless he--no, there is a way. He could've had a mutation in the gene that turned it from a brown into a blue gene, and that could've found its way into the sperm that fathered the child; and the probability of that happening is about 10-9. Okay. See if you can explain that. Take--print this list out. Sit down at lunch with a colleague from class and see what you can't explain. Take that term into section and get it explained. Okay? Next time, Adaptive Evolution.



[end of transcript]

Adaptive Evolution is driven by natural selection. Natural selection is not "survival of the fittest," but rather "reproduction of the fittest." Evolution can occur at many different speeds based on the strength of the selection driving it. These types of selection can result in directional, stabilizing, and disruptive outcomes. They can be driven by frequency-dependent selection and sexual selection, in addition to more standard types of selection.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 2

Transcript



January 16, 2009



Professor Stephen Stearns: Today we're going to talk about adaptive evolution, and that means that today is going to be all about the different kinds of natural selection that there are. It's going to be about the vocabulary that evolutionary biologists use to describe selection. It's going to be about rates of evolution, why evolution is sometimes very fast, sometimes very slow, and it's going to be about the different contexts in which selection occurs. So we'll talk a little bit about sexual selection. We'll talk a little bit about group and species selection, things like that. All of these things that I mention today are going to be coming up again and again. So this is just part of the intellectual toolkit for dealing with the course.



This is an outline of the lecture, and since it's a whole lecture it's in pretty small type, and I don't expect you to read that off the board. But I do want you to have it so it makes it easy for you to review this when you download it and you look at it in your notes, because it does summarize the main points. Basically what I'm going to do is tell you that evolution can be either adaptive, in which case it has been driven by and shaped by natural selection. It can be neutral, in which case it's been dominated by drift. Or it can be maladaptive. So evolution does not only produce things that work well. Evolution produces things in which stuff can go wrong, and sometimes evolution just wanders around.



Now adaptive evolution is not about the survival of the fittest. That is a phrase invented by Herbert Spencer, in the nineteenth century, that has had a long shelf life, and it's wrong. Adaptive evolution is about a design for reproductive success. It's all about how many children and grandchildren you have, and whether you do it better than somebody else that's in the population. It's always relative.



Natural selection is like the tale about the Buddhist monk and the disciple who were attacked by the tiger and the disciple says to his master, "Oh Master, we're going to be killed because we cannot possibly outrun the tiger," and the master says, "No, I just have to run faster than you." Well, selection is always relative; it always depends on what the picture is of reproductive success in that population at the time that it's happening.



Now I'm then going to discuss when selection is strong and when it can be slow, and I will tell you something about the rate--the units in which evolutionary rates are measured, and then I'll run through types of selection. Now there are going to be two questions that pose puzzles that come up in this lecture. One is going to be what will happen, if directional selection continues for a long time, can that continue, and if it has to stop, then why should it stop? And the other question will be how can we explain that even though evolution can really be extremely fast, that sometimes things don't change for hundreds of millions of years? So you have to be able to come up with enough intellectual tools to be able to handle that range of variation in evolutionary outcome.



Both of those things really do happen: nothing for a long period of time, or incredibly fast. So here's incredibly fast: antibiotic resistance. It is a curious and striking cultural fact that in the United States, when people talk about antibiotic resistance in television and in the newspapers, they almost never mention the word 'evolution.' They say it emerges or it develops. But, in fact, this is the poster child for rapid evolution.



You can see here roughly the years in which antibiotic resistance emerged, evolved, in these diseases. If we develop a new drug and release it in the UK in 2009, resistant strains of bacteria will have evolved and will be in hospitals in the UK within six months, and those resistant strains of bacteria will be observed in hospitals in Hong Kong within two years. The bacteria will have moved around the earth as people move around the earth. The drug industry is in a co-evolutionary arms race to try to keep up with the bacteria that evolve resistance, and we have gradually been losing the arms race.



So if you read in the newspapers about multiply resistant staphylococcus aureus, which is MRSA, it is starting to crop up now out in the community. It's not just confined to hospital emergency wards and intensive care units anymore, it's starting to spread. And if staph aureus picks up resistance to vancomycin, which is one of our last lines of resistance against it, it's going to be very difficult for surgeons to do operations in the confidence that they can keep their patients from dying after they have surgery. So this is serious stuff.



Most resistant bacteria live in hospitals, because that's where most antibiotics are used, and the number of hospital acquired infections is about two million per year in the United States, and it's estimated that about 90,000 people who did not have a bacterial infection when they went into the hospital, got into the hospital and then died from that bacterial infection. And, in fact, it looks like this is a serious underestimate because this is the official report, but if you look at what the hospitals asked for, in terms of money from the insurance industry, it's about ten times higher than that, OK?



So, by comparison, this is how many people are dying in 2005 from AIDS in the United States, influenza and breast cancer, and you take that and you multiply it to the planet and you can see that the evolution of antibiotic resistance is a pretty serious issue. The economic burden in the US four years ago was eighty billion a year, and this is a problem which is caused by strong directional natural selection, eliciting a rapid evolutionary response. So in the next few slides I'm going to be talking about what I mean by directional and what I mean by rapid.



By rapid, in this case, if you have a normal sized bacterial population in your body and I give you an antibiotic, the probability is that if you don't do your antibiotic treatment correctly, within about a week or two you will have resistant bacteria in your body. Finish your antibiotic treatments, never stop in the middle, OK; kill them all off.



Here's a good example of rapid evolution in nature in a fish in ecological time. It's one of a series of cases that accumulated in the 1970s and 1980s that demonstrated that evolution isn't all about dinosaurs, and millions of years, and slow, steady change. Evolution in stuff like the color of the male's body, the number of babies the female has, how fast they grow--all kinds of ecologically and behaviorally important properties can happen real quick.



This was done by doing an experiment in which guppies interacted with predators. This is a cichlid fish Crenicichla. This is the pike killifish Rivulus, and it was done in Trinidad, by David Reznick who is at Riverside. Now the setup in Trinidad basically is that there is a mountain range on the north end of the island, and there are lots of little streams that are going down the mountain range into a river and they go over a waterfall.



And the fact that the stream goes over a waterfall has prevented the large predators from getting up above the waterfall, and above some of the waterfalls there were no fish at all. So what Reznick did was he took fish that had evolved for a long time, with predators below the waterfalls, and he put them above the waterfalls, and he did replicates. It was a nice system. There were lots of streams. You could do it four or five times, to make sure it was a consistent pattern.



And these are the results. The life history traits--that means how big they are when they're born, how old, and how large they are when they mature, how many babies they have and how long they live--all evolved rapidly. So they responded quickly. The fastest rates of evolution were measured in things that occur early in life. So the number of babies in the first brood, how big the babies were in the first brood, how fast the babies grew, that all changed quickly.



And basically the pattern was this. If the guppies are under a high predation regime, they mature earlier and they have more smaller offspring, they have a shorter life--this all has something to do with the evolution of aging and why we grow old and die--and they had more smaller offspring. Okay? The males were less colorful and they displayed more discretely.



Guppy courtship is normally a fairly elaborate thing. The male, who you can see is really brightly colored, also has an elaborate display behavior, and he will dance up in front of the female and he will wave his fins back and forth and then he will dart in and try to mate. And the females prefers males who have bright orange spots. The bright orange spots probably were originally a direct indication that the male was good at catching crustaceans, because crustaceans have carotenoids in them. So they catch amphipods and shrimp and things like that, and then reprocess the chemicals and they can make orange with it. That was an indication that a male was a good forager, and so the female might select that male because then her babies also would be good at catching food.



However, the male is dancing in front of the female, and that makes him a sitting duck for Crenicichla (Pike Cichlids) And as we'll see a little bit later in the lecture, sexual selection involves a direct tradeoff between mating success and survival, and these guys were displaying frantically to get mating success, at the risk of being snapped up by a predator, and the ones that survived were the ones that simplified their display behavior. Okay? So this all happened pretty quick.



Now how do we measure it? Well currently--and there's been a bit of controversy about this--but currently the preferred unit of measurement is a haldane, and a haldane is a change in the mean value of the population by one standard deviation per generation. So I'm going to tell you what a standard deviation is, and I'm going to tell you who Haldane was.



Haldane was the son of the Lord Admiral of the British Navy who commanded the British Navy in World War One. And he was a brilliant polymath. He was fluent in Greek and Latin, as well as mathematics and biology, and he did foundational work in biochemistry and on the origin of life, as well as in population genetics. For many years he was a professor at University College, London. He was a Communist and a Socialist, and a social reformer, who had a romance with the Soviet Union and then became bitterly disillusioned when he discovered what had gone on in the gulags in the 1950s.



When he got intestinal cancer he retired from his position in London and he took a job in India and he taught a whole generation of population geneticists in India before he died in 1962. A very interesting guy, and actually there is a lot about the social impact of science that you can learn from reading about J.B.S. Haldane. The biography is just called JBS.



This is a standard deviation. It is an empirical observation, supported by an elementary theorem of mathematical statistics, called the Central Limit Theorem, that most population distributions look like a bell-shaped curve. It's called the normal distribution. It was formalized by Gauss; sometimes it's called a Gaussian distribution. And the shape of the curve and its spread are basically measured by the standard deviation.



So the mean value is at the center here and the distribution is theoretically symmetrical--in practice it's quasi-symmetrical--and the degree of spread is measured by the standard deviation units. So within 1 standard deviation you will find, on each side, 34.1, or with both 68.2% of all of the individuals observed in the population.



So 1 haldane basically would take a population that say had a mean value--suppose it was for body size, maybe a body size of 10 grams--and if it had a standard deviation of 2 grams, and it was evolving at a rate of 1 haldane, it would move that mean from here to here; 1 standard deviation unit up, and the population mean in the next generation, instead of being 10 grams, would be 12 grams. So that's the meaning of the haldane.



Here are some measured haldanes. Okay? So for those guppies in Trinidad, that were evolving pretty fast, the number of spots in the area of orange spots--when you took away the predator and suddenly being brightly colored wasn't risky anymore and females liked it; so it was good to be brightly colored--those spot numbers increased quickly. They were increasing at about .7 haldanes.



In the Galapagos finches that Peter and Rosemary Grant studied, they go through El Nino, and during El Nino--it's a strong selective event, so about every ten years there's a strong selective event on the Galapagos finches--and during El Nino they were evolving at about .7 haldanes in body size; they're getting bigger. And then in the other years they were getting smaller. So they fluctuate, they go up and down, depending upon the El Nino conditions in the Galapagos.



There have also been lots of measurements of slower rates; for example, since the extinction of their competitors in the late nineteenth century the surviving Hawaiian honeycreeper, the I'iwi has been evolving a shorter bill, and that's been a very slow rate of evolution. The migratory timing of Columbia River salmon has been changing as a result of the human fishery on them.



All of the fished populations of the world are evolving under the pressure of human fishing. Most of the fish in the world are getting smaller. Many of the stocks are collapsing. It's producing a change in the time of year that the Columbia River salmon run up the Columbia. This is also due to the building of dams on the Columbia. So this is a human induced selection process. These are fairly slow rates.



So what does this mean, if we just try to think about these rates and evolutionary times? A Galapagos finch is about 25 grams, about the size of a house sparrow. They evolved during El Nino at about half a gram a year. What if the El Nino conditions persisted forever? What if it wasn't the southern oscillation that was driving the rainfall pattern in the Galapagos? What if it just stayed warm and wet for a long time in the Galapagos? Well that would produce directional selection, and if you did it for a hundred years, it would turn a 25 gram finch into a 75 gram finch. Basically it would take a finch and turn it into a small robin. Okay? If you did it for 10,000 years, it would turn it into a turkey.



Now finches as big as turkeys don't do very well in a finch habitat. They are living in a place where they hop around in bushes. They are living in an environment in which food is sometimes very hard to come by. I've been observing the turkeys that live near my garden in Hamden, trying to get up into the trees next to Lake Whitney to pick the berries off as winter has come on and it's gotten very cold. They're pretty clumsy.



So what will happen if you keep a strong directional selection going on finches? What would happen to humans if there were strong directional selection on humans to increase in body size? What would happen if we got turned from say 50 to 80 kilo primates into three-ton primates? How long could that go on?



One of the fastest rates of evolution ever measured in the fossil record was when elephants went onto islands in the Mediterranean and turned from twelve-ton elephants down into things about the size of a Saint Bernard. Okay? They did it in less than 100,000 years. They did it because they were food limited and they'd been released from predation pressure. Okay?



So how far can that process go? These are quick changes that we're describing. The finches are moving pretty fast. The guppies are moving pretty fast. The elephants change pretty quickly. But if you look over the whole spread of evolutionary time, over hundreds of millions of years, things stay within a fairly narrow envelope of body sizes. Why does that happen? So if we look at microevolutionary rates--and by the way there are good papers on this. If you're interested in rates, this is a good paper topic. Umm, lots of measurements, lots of argument about why.



They vary from very fast to very slow. The fastest are in the finches and in the Trinidad guppies. There have been lots of rates measured in Hawaiian mosquitofish and Hawaiian honeycreepers. So there are lots of estimates available. And interestingly, the shorter the period over which the rate is measured, the greater the maximum rate. So if you measure a rate by making comparisons between two populations that have been separated for hundreds of years or hundreds of generations, it's usually fairly slow, and if you focus in and you just look at a brief period, it can be very fast.



Why do you think that might be? Why might we measure a faster rate when we do so over a shorter period of time? If we measure it over a short period of time, sometimes it's faster. If we measure it over a long period of time, it's slower. Does that suggest anything about what the pattern might look like that I'm about to draw on the board? Yes?



Student: [inaudible] So it can go up and down, and [inaudible]



Professor Stephen Stearns: You got it, that's all it takes. It just has to go up and down. If I measure it over this period, it looks pretty fast. If I measure it over this period, it looks pretty slow. That's all it is.



Okay, the take-home message, from many studies done in the '70s, '80s and '90s, is that evolution can be very fast when populations are large and selection is strong. And the reason for that is that big populations have lots of genetic variation. So there's a potential for a big response to selection. Small populations don't have so much genetic variation. So even though selection might be strong, they can't respond so well.



This point, the shorter the time interval over which you measure the rate, the higher the maximum rate. And here's one reason why you can't take Galapagos finches and turn them into turkeys and then turn the turkeys into ostriches and then turn the ostriches into moas and then have the moas turn into tyrannosaurus rex. Okay? As you push things very far, in any direction, there's an internal process that converts the directional selection into stabilizing selection. And those are the tradeoffs, the linkages among traits.



If you try to make a finch very large, then although it may be gaining something in terms of say food capturing ability, it is giving up maneuverability. If you try to take elephants and make them very small, then at some point they are not going to be able to compete with other elephants for food supply, even though there may not be any predators there. There are all kinds of biomechanical linkages within bodies where tradeoffs are involved.



So if you look within the organism, you see that it's a bundle of linkages and compromises, and every time you try to change one trait you have a byproduct, you have an implicit selection going on, on other traits. So although you may be realizing a benefit in one, or a place, you are paying a cost in the others.



The most striking example we've seen of it in the lecture so far is the guppy, the male guppy. If he evolves to be bright and a wonderful dancer, so that females just love to mate with him, he will get killed by a predator. That is about as straightforward and brutal a tradeoff as you can imagine. Okay? But these go on all over the place and some of them are very subtle.



Now why is it that sometimes traits evolve very fast and sometimes very slow? This is a picture of clubmoss, lycopodium. If I were to take you out into the woods of Connecticut in the springtime, you would see them all over the place, and if I were to put you a time machine and take you back 400 million years, they wouldn't look any different.



This is latimeria, this is a Coelacanth. If I were to put you into a research submarine off the Comoro Islands in the strait between South Africa and Madagascar, between Malawi and Madagascar, and we went down at night to a depth of 300 to 600 feet off the volcanic slope of the island, we would find these guys cruising around in mid-water. They have spent the day in caves and they come out at night, into the mid-waters of the earth's oceans, and apparently they have been doing this now for going on 150 million years.



They haven't changed at all. By the way, they have an egg the size of an orange. They're interesting. They're, they're pretty effective predators too. They are, uh, ambush predators. They drift around and then they suck things into their mouths by a big kind of vacuum suction device. It's a common method of fish feeding. So they're living fossils. Now why haven't they changed?



Look at what's happened to their relatives. The clubmosses had relatives at the time that looked about like them, that since then have turned into redwood trees, orchids, wheat fields--you name it, these guys still look the same. Latimeria had relatives that since then have turned into marlin and reptiles and birds, mammals; it hasn't changed.



So we have these two things to understand. We have to understand how evolution can go really fast--antibiotic resistance, guppies, finches--and why sometimes it is so slow. Any ideas on this one? Is this the first time you've hit this problem of why evolution is sometimes so slow?



Student: It finds a pretty stable way of living and surviving, and sometimes way down below depths of the ocean [inaudible]. Might not that change the effect of latimeria? And the clubmoss are in [inaudible] for hundreds of millions of years, while [inaudible].



Professor Stephen Stearns: Right. Okay, that's one kind of explanation, and I think it's certainly a plausible one. It's not the only one, but it's certainly one kind. So his argument is the reason these guys haven't changed is that they're really good at always finding the same kind of environment, so that they are never exposed to change. So if their environment moves around the globe, they track it.



Now remember, between 140 million years ago and now, the earth went through a huge meteorite strike, the dinosaurs went extinct. Heavy stuff happened back there at the end of the cretaceous, and latimeria just cruised around and it hasn't changed very much. Now the argument is actually probably most convincing for marine invertebrates, that make larvae that can go out and spread through the ocean for thousands of kilometers.



And, in fact, we know from the behavior of marine invertebrate larvae--so now I'm talking about worms, barnacles, clams, stuff like that--that they like to settle on places where there are successfully growing adults of their own species. They smell that out very carefully, and that's where they settle. So basically the larvae are selecting the habitat in which the adults will be selected by natural selection. That means that they manage themselves to generate stabilizing selection over hundreds of millions of years.



That's, and arguably latimeria has done the same thing. It's been living in lava tubes on the sides of submarine volcanoes at 300 to 1000 feet, for a long time, and that habitat's always been around. Any idea for another explanation of stasis? That's an externalist explanation. Okay? It relies on aspects of the habitat and the way natural selection is operating on the organisms. Anybody got an idea for an internalist explanation? Yes?



Student: There are genetic mechanisms that will regulate DNA copying and improve [inaudible] application.



Professor Stephen Stearns: I very much doubt that a lack of mutations was ever the reason that things didn't change. You've got 4.6 in you that're new since your mom and dad, for example. Yes?



Student: All populations are a [inaudible]



Professor Stephen Stearns: Well, yeah, the problem with that over a long period of time Greg is that if it's really a small population it's more likely to go extinct, and these things are out there for hundreds of millions of years. So that one's a little difficult. Other ideas?



Well there's a whole school of thought that says that this kind of thing is due to developmental constraints; that development has constrained the organisms so that they couldn't evolve in certain ways. And that's plausible for certain major features of the body plan, that are determined very early in development, and involve developmental tissue relationships and things like that, that are obviously hard to change. It's not so plausible for some of the smaller details of these creatures.



So I think that the actual explanation is probably a mixture of these things. There probably is some phylogenetic or developmental constraint. Things that happened a long time ago, in the way organisms were built, are hard to change, and they've been constraining the things that can change more rapidly. But I think you'll find, if you get into this, that it's a huge and controversial literature on it. Okay.



Kinds of selection. Now we go through another one of these vocabulary building exercises, and I'll try to illustrate a few of these. But I just want to get these words out there and I want to get them into your minds so that you can start to think about the fact that natural selection comes in lots of different flavors. We can talk about directional, stabilizing and disruptive selection; natural and sexual selection; frequency dependent selection; and then selection acting on individuals, on kin, on groups and on species. So each of these is cutting the selection cake in a different direction; but it is all of these different things.



So, directional, stabilizing and disruptive. Basically what's going on with directional selection, that's making the Galapagos finch into a turkey, is that the fitness gradient is linear. That means that if the fitness of something over here is low and up here is high, that means that natural selection is selecting for say bigger things--this body size on the X-axis is going to the right--and it will take a distribution that looks like this and it will move it to the right. So if this is 1 standard deviation, then this amount of movement is 1 haldane, right here.



Stabilizing selection is actually what we were just invoking to argue that the coelacanth didn't change. It was living in a habitat where it was always good to be like a coelacanth, and natural selection was selecting out things that didn't look like coelacanths; whether they were larger or smaller, or their fins were different shapes, or things like that. So they tended to stay the same.



That means that we were selecting for the mean of the population and we were discarding the extreme values. Who in the room is under 5'5, and also who in the room is over 6'1? Raise your hands please. Okay, if there's stabilizing selection on human height--you guys have no grandchildren. Can I see the hands of everybody else? Hey, you made it. Okay? That's stabilizing selection. It means selection for the mean value, and it's selection against the extremes. Be happy that that doesn't appear to be the only thing going on in humans.



Disruptive selection is selection against the mean and for the extremes, and it will take a bell-shape curve like this, it will knock out the mean value, and then the next generation it will push it apart like that. Okay?



So if we look for examples, strong directional selection will produce very rapid evolution. We saw that with antibiotic resistance and the guppies. It can't continue. It usually gets converted into stabilizing selection. Disruptive selection causes, historically, things like the conversion of similar looking gametes into quite different gametes.



So disruptive selection was involved in the origin of eggs and sperm, back in the day, about a billion years ago, and it may play a role in sympatric speciation; which we will come to, um, probably in mid-February. So just remember that. Disruptive selection is selection to take a population that has a certain mean value and split it in half and turn it into two different things.



Now, natural and sexual selection. We've referred to sexual selection with the guppy. The classic example of sexual selection is a peacock's tail. This is actually what inspired Darwin to come up with the concept. He said, "Look at that peacock. There isn't any reason, from the point of view of survival, for a male peacock to be that colorful, and have that big a tail, and have this absolutely exotic behavior of dancing around, waving its tail."



And, in fact, if you look at the birds of paradise, the amazing thing about the birds of paradise is not really their feathers, it's what they do with their feathers. They do fan dances with their feathers. They can do the rumba, they can shake, they can rock and roll. They do all kinds of stuff, and they're all dangerous, because they're out there displaying and predators could come along and eat them. Okay?



In fact, peacocks are eaten by tigers, or they were eaten by tigers before the tiger just about went extinct in India; they're down to a few hundred in India, and the Siberian tiger is under threat right now in Siberia. But the tigers traditionally ate peacocks. They really did. So the display behavior was dangerous. So what the male was doing was he was trading off survival for mating success. He was a victim of female preferences. [Laughter] Don't tell that to the fraternity guys, okay?



So, sexual selection is a component of natural selection. Natural selection is all about variation in reproductive success, and you can achieve reproductive success by mating and by surviving and by doing other things. Okay, so it's a component of natural selection. And the tradeoff involved is survival versus mating.



It's driven by two things. Either ma--either the males are competing with each other for access to females, or the females are conniving against each other for access to males--one of those processes may drive intelligence a little bit more than the other--and it's also driven by members of one sex choosing mates of the other sex. So we're going to have a whole lecture on sexual selection. It's often fun to write a paper on this topic. There are several criteria that one sex might use in choosing a mate.



One is a direct benefit. So with birds that would be, "Oh, that male's got a really good territory, it's got a lot of food in it; therefore I could have a lot of babies and raise them there, so I'll go live in that territory." Not so directly looking at the male, just saying, "Oh, he happens to hold that territory." That would be a direct benefit.



Or you could say, "Oh my goodness, isn't he sexy? If I mate with him, my sons are going to be sexy too." [Laughter] That's called the sexy-son hypothesis, and actually it does appear to drive some of the more extravagant displays, and is probably responsible for the evolutionary shaping of the peacock's tail.



A third hypothesis is, "Oh he's resistant to disease, and he happens to be wearing a piece of morphology, that I can detect externally, that tells me that he's resistant to disease; because it's expensive to produce and only resistant males are capable developmentally of producing it."



There's an interesting principle involved in that. Basically it is that honest signals are costly. Okay? And if disease resistance is costly and you can advertise your resistance with a signal that you are disease resistant, then that could be something that a female preference might then evolve to notice.



We'll go into that, but you can see immediately that if the signal is not costly, then it can be invaded by cheaters, and then as soon as there was cheating going on, the female preference would erode, because there wouldn't be any point to having that preference; you were getting cheated on too frequently. Yes?



Student: I just have a question about the sexy-son hypothesis.



Professor Stephen Stearns: Yes.



Student: It seems like it implies a certain psychology in the mother that's kind of expensive to have.



Professor Stephen Stearns: Yes it does, doesn't it? And isn't it interesting that things that we find beautiful evidently are also preferred by female birds and by bees that are locating flowers and things like that? It implies a whole set of innate preferences in choice. It doesn't imply necessarily consciousness; I mean, you can build robots that will do this. But it does imply a fairly costly choice apparatus, which appears to have evolved.



Frequency dependent selection is another kind of selection, and that happens whenever the advantage of doing one thing depends on what the other people in the population are doing. Okay? There are some classical examples of this. One is the classical 50:50 sex ratio, and another is genetic diversity for immune genes. I'll just say a few words about genetic diversity for immune genes, because we're going to come back to sex ratios when we do sex allocation theory.



Let's suppose that you have a gene that is resistant to a particular disease, and therefore your offspring survive better and you have more grandchildren, and this gene then spreads through the population until eventually most of the people in the population are resistant. That means that there's selection operating on the disease to come up with a variant that can overcome that resistance, and when that variant comes up, it will spread until it is common, and it creates selection to cause the same thing going on in the host population, and back and forth it goes.



The more frequent something becomes, the more it's subject to very strong negative selection, and the less frequent it becomes, the more it's protected from being selected, because things that are rare aren't very good resources; things that are common are great resources. And so what happens is that you get what is now recognized as a classical oscillation of virulence and resistance between the host and the pathogen.



One of the most interesting things about a human immune system is that the MHC or HLA genes that mediate this kind of resistance against pathogens have some of the highest genetic diversity of any genes anywhere. It looks like variants, rare variants, have been selected again and again and again. So every time something becomes frequent, it becomes useless and another rare one is selected, and eventually a huge supply of variation builds up in the population. So this principle really has had quite a role to play in the selection of the vertebrate immune system.



Okay, group selection and species selection. I'll go through this fairly quickly. We're going to come back to this issue when we do behavior in, um, April. Okay? But group selection--here's an example of group selection. A bunch of partridges get together in Scotland in late fall. They look around. They notice that there are just a tremendous number of partridges in Scotland in late fall, and they think--you know, speaking anthropomorphically--they think, "Oh, there are too many partridges. Therefore we will all cut back on our reproduction so that our population does not go extinct."



That's an example of group selection. It won't work because over in the corner is sitting Joe Partridge, who looks at all of these guys and says, "You're idiots. You're cutting back on your reproduction. I'm going to have 50 babies." [Laughter] Group selection is vulnerable to selfish mutations; selfish mutants invade. Okay?



So they invade for a variety of reasons, and we'll work through all of that. But group selection is not stable. Selfish mutants invade. They do so. There's a lot of selective events in genes and individuals for each selective event of a whole group. And if you extend group selection up to species--how many times have you guys ever heard, perhaps on Discovery Channel or BBC or National Geographic, that behavior X or morphology Y exists for the good of the species? Have you ever heard that? Yes, it happens a lot.



It's bullshit, just plain bullshit. Okay? Things don't exist for the good of the species. Things exist because individuals outperformed other individuals in the competition for reproductive success. Now there is some large-scale differential species selection that occurs on the phylogenetic tree, and it shapes patterns at a big macro scale across the tree.



One of them is sex. Virtually all asexual things are relatively young and they had sexual ancestors. It appears that sex reduces the probability of extinction, and that asex makes you more extinction prone. So that is a kind of species selection. But it's not a selection for a precise adaptation. There's no way that species selection could have ever designed the vertebrate eye, the vertebrate brain, any of the detailed, precise, complicated mechanisms that we know of in biology. All that stuff has gone on because of individual and gene selection.



Some of the big macro evolutionary patterns have been generated by a kind of species selection. For example, the fact that dinosaurs aren't here anymore and that mammals dominate the earth is a kind of selection. It doesn't tell you about how fast the mammals run, why they are warm-blooded, ta-da da-da da-da. Dinosaurs were warm-blooded too.



Okay, we can classify selection a number of different ways. Each one, each of the methods of classification, highlights a distinction. Selection can be strong and the response can be fast, but some traits evolve very, very slowly. And you need to be able to hold those two facts in your mind, and have intellectual tools that will allow you to deal with both situations. Okay, next time Neutral and Maladaptive Evolution.



[end of transcript]

Neutral evolution occurs when genes do not experience natural selection because they have no effect on reproductive success. Neutrality arises when mutations in an organism's genotype cause no change in its phenotype, or when changes in the genotype bring about changes in the phenotype that do not affect reproductive success. Because neutral genes do not change in any particular direction over time and simply "drift," thanks in part to the randomness of meiosis, they can be used as a sort of molecular clock to determine common ancestors or places in the phylogenetic tree of life.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 3

Transcript



January 21, 2009



Professor Stephen Stearns: The lecture today is about neutral evolution. So let's get going on that. I want to remind you, when people think about evolution they often think that it's only natural selection. But it's not. It is both micro and macro. So macro gives us history and constraint, and micro consists basically of natural selection and drift; and developmental biology is involved in both.



So what we're going to talk about today is basically neutral evolution. What happens to genes or traits that are not experiencing natural selection because they're not making any difference to reproductive success? There's actually a lot of that that goes on, and it's very useful that it does. It gives us a baseline, it gives us a method of measuring things, and it gives us a lot of information about history.



So there are going to be three messages I want you to remember today. One is going to be how meiosis is like a fair coin. The probability that a gene will get into a specific gamete in meiosis is 50%. The second point is how the fixation of a neutral allele in a population is like radioactive decay; and it's like it in this sense: in neither the case of the fixation of neutral alleles, nor in the case of say looking at a gram of uranium-238, do you know which mutation will be fixed or which atom will decay. But, because there's so many of them, in both cases you know very precisely how many events will happen in a certain period of time. Okay?



This is a kind of law of large numbers for random events. If a lot of random events go on, the average is a very predictable thing. But if you just examine one nucleotide in a genome, or one atom in a gram of uranium, you can't predict when it will mutate, when it might be fixed, when it will decay.



The third thing that I want you to remember is this regular fixation of neutral alleles, this steady process whereby if you look at an entire genome, over a given period of time--10,000 years, 100,000 years--a certain very predictable, average number of mutations will be fixed if they're neutral. So if you can locate the neutral ones in the genome, you can use them to estimate relationships and the times to the last common ancestors. Okay?



So there's actually some interesting, rather abstract and rather big ideas in this lecture. Randomness is not something that everyone finds intuitive. Our brains are apparently not designed by natural selection to deal extremely well with Las Vegas, or the stock market. Okay? So we need to hone your intuition a bit about how random processes work.



By the way, people who do really well in calculus and analysis often find their introduction to probability and statistics a little confusing. The thing that's going on here is that you have to learn to think about entire populations of things and about distributions and frequencies of things, rather than about billiard balls hitting each other on a table or planets being attracted to the sun, by gravity. It's a different kind of thinking. It's population thinking.



So the outline of the lecture is a bit about how neutrality arises. I want you to know mechanistically why it is that some genes are neutral; the reasons why genetic variation might not produce any variation in fitness--that's what we mean by neutral, there's variation at one level but it doesn't make any difference to reproductive success; the mechanisms that cause random change; and then the significance of neutral for molecular evolution. And now I'm briefly going to mention maladaptive evolution so that you can see how it is that an evolutionary process can actually result in a situation where organisms are not well adapted to their habitats. And with that we will have covered the major possible outcomes of evolution: adaptation, neutrality and maladaptation.



Okay, here's a nice abstract diagram to explain why neutrality arises. What I want you to imagine is a genotype space in which all possible genotypes for that organism might occur. Just think about that as being all the different ways that you might have been constructed if all of the possible recombination events in your father and mother had produced all the possible gametes and all the possible zygotes. There's a genotype space for you.



Many of those genotypes will produce the same phenotype, and that's because many of the genes and many of the nucleotides in the genome, many of the DNA sequences in the genome, are not making any difference to the proteins that are being produced. There are other things going on and we'll run through them. Many phenotypes have the same fitness.



How many of you come from one-child families? Okay, all of your parents have the same fitness. How many from two-child families? All of your parents have the same fitness. Okay? This happens a lot. Basically when we say that many phenotypes have the same fitness, we just mean that in any population there will be a lot of organisms that all have two offspring or all have three offspring or something like that. The two offspring class all have the same fitness.



Then when we look at the whole halfway [this would only make sense when looking at the figure] here, we can see that G1, G2 and G3 are neutral with respect to each other, when measured in a certain environment, but they differ from G4. So here we have a lot of genetic variation that's neutral, and it's neutral for various reasons. We're going to run through some of those reasons.



First, some of the mutations in DNA sequences are synonymous. That means they don't produce any change in the amino acids that are coded in the proteins. Secondly, there are pseudogenes and other kinds of non-transcribed DNA in the genome. A pseudogene is a gene that resulted from a gene duplication event sometime in the past and never got used to make anything. And if you go through an entire genome, which you now can do for many organisms, looking for these things, you will find that they're all over the place.



There have been many gene duplications in the past, and some of them resulted in genes that were then acquired by selection and used developmentally for some function. Others were not. The pseudogenes are the ones that weren't used. Their usual fate is to be eroded by mutation. So gradually the useful information that was once in them gets destroyed by mutation, and if they sit around long enough they are no longer detectible; you can't tell anymore that they were once really a functional gene, before they got duplicated.



There's neutral amino acid variation, for a variety of reasons. Some amino acids have very similar molecular size and charge properties, so that if you substitute them in a protein they don't really make much difference to the shape or the charge distribution on the protein. And if you look at a whole protein, which is usually a pretty big thing--say if it's an enzyme--normally it will have an active site that is in a very small spatial portion of it, so that the amino acid substations that are occurring right at the active site are making a big difference to its function, and then potentially down the line to fitness, and the amino acid substitutions that are occurring a long way from that active site are having little impact on the function of the protein, even if they have a different size or a different charge structure.



So there's neutral amino acid variation, and finally there's something which is a little bit more abstract, and basically it's abstract because we don't understand it very well--it's a real phenomenon but we don't always know what the mechanisms are--and that is the canalization of development. So I'll run through these and then try to explain canalization a little bit in a few slides.



Here is, uh, the genetic code, and basically you can see here the nucleotide triplets that are translated into the various amino acids. And the take-home point, the first take-home point from this, is that for any particular amino acid--phenylalanine, for example, here there are two codes for phenylalanine, and look there are six codes for leucine. So any changes within this set of nucleotide sequences produce no change at all in the amino acid that goes into the protein. They are neutral with respect to each other, because they're synonymous.



And you can get some hint of another level of synonymity by looking at the classes of positively-negatively charged amino acids, aromatic amino acids and so forth. Substitutions between aspartic acid and glutamic acid, that are both negatively charged, are less likely to make a fitness difference than a substitution say of lysine, for glutamic acid. So there is a level in the protein as well.



The pseudogenes I've talked about a little bit. They are not transcribed and all of their nucleotides are free to diverge at random. That means that there is no real editing process going on--natural selection isn't preferring one mutation to another. It's not any more likely to turn up in children or grandchildren than another. This gene has been turned off, and it will inevitably get eroded because all DNA sequences are subject to mutation and if a mutation occurs in a pseudogene, there isn't any particular reason for repair mechanisms to pay any more attention to it than they do to anything else. Okay?



So these things are not especially repaired by repair mechanisms and they're not at all repaired by natural selection. So this comment will apply to a lot of the DNA that's not transcribed. Now fifteen, twenty years ago, when this class of DNA was discovered, people labeled it 'junk DNA' because they didn't think it did anything, and of course it's been then the pleasure of younger scientists to show the older ones that this stuff actually often does have a function--usually it's a regulatory function. Some of it makes small RNA molecules that are used in regulation, but some of it is also being used as, uh, sites and signaling pathways and helping to regulate development.



However, some of it truly is junk. For example, there is a steady process by which viruses of various sorts splice themselves into the genomes of their hosts, and this is part of the adaptive strategy of viruses that they are able to hedge their bets by sticking themselves into a genome and hanging around for awhile and then popping out, at a point which might be advantageous to them but inconvenient for their host.



However, it's a dangerous strategy because sometimes they stick themselves into parts of genomes that never get transcribed, and they never get out. So in fact the genomes of most of the organisms on earth are littered with the fossil skeletons of viruses. I read an estimate once that the human genome had a substantial percentage of fossil viruses in it. I have forgotten the exact figure at the time. This kind of thing was popular when DNA sequences were first starting to come out in large numbers. But just know that. Okay?



So there is junk DNA, and some of it's there because either fossil viruses or transposons, jumping genes, got into positions where they could no longer be transcribed, and they then become a graveyard. Kind of an uncomfortable thought isn't it, that you're just carrying around a viral graveyard? But you are.



Okay, neutral amino acid variation. I've talked about this a bit when I introduced the genetic code. So these are amino acid substitutions that aren't producing any change in geometry or any charge change in the geometry and electrochemistry of a functional site within a protein. And I'd like to talk a little bit about a very early case of molecular evolution; that's the case of alpha-globin. So your hemoglobin has two alpha and two non-alpha chains. It has a beta chain if you're an adult and it has a gamma chain if you're an embryo. The reason it changes from a gamma to a beta is to change the oxygen binding properties, because embryos have to suck oxygen out of their mother's blood. Okay?



If we look at these alpha-globin sequences, across a pretty broad range of vertebrates, and we take samples in such a way that we can look fairly far back in time, we can date these branch points approximately from the fossil records. Okay? So dogs and humans shared an ancestor probably somewhere late in the Cretaceous, mid--late mid-Cretaceous. Our last common ancestor with the kangaroo was at about 140 million years perhaps. The mammals were there while the dinosaurs were there. They were just small little guys, but there were mammals there. Our last common ancestor with the shark is back at about 440 million years.



So take the sequences for all the alpha hemoglobins that you pull out of these things--it's a convenient molecule, you just need a blood sample--and plot them on a graph. So you estimate the time from the fossils and you estimate the average differences. This "k" is a measure of amino acid differences in a protein, and the straight line is what you would expect to get if the rate of amino acid substitution is random, just uniform, just steady. Okay?



It's pretty close to the line. There are some deviations. But this is some of the earliest evidence--this was before DNA sequencing became easy, this was when protein sequencing was easier than DNA sequencing--this was some of the earliest evidence that there's something like a molecular clock. In other words, if we got a vertebrate that we'd never seen before, living in some forgotten jungle, and it had a weird morphology and we didn't know who its relatives were, and we wanted to find out when it might have shared an ancestor with something that we had, and it plotted right here--its difference with something that we were comparing it with right now, plotted right here--then we would have a good estimate of time to last common ancestor, for that new, undiscovered species, based on the assumption that it was experiencing evolution like all these other guys.



Okay, the fourth reason why genetic variation might be neutral is canalization. Now canalization in general means that there are developmental mechanisms that are limiting the range of phenotypic variation, so that even though there is a mutation in the genome, or there is a disturbing environmental effect on a genetically controlled pathway, that you're still going to get the same phenotype.



Some things about your phenotype are extremely stable. They do not respond to mutation much at all. The fact that you have four limbs, the fact that you've got five fingers; things like that are ancient and stable and there are developmental buffering mechanisms that keep them that way. So these things, these canalizing mechanisms, resist the tendency of variation in either genetic or environmental factors to perturb the phenotype; they keep it in a stable state.



So what happens to the genes that are forming this phenotype but they're being buffered by these developmental mechanisms? Well they are then freer to accumulate neutral variation, because basically the fitness consequences of a mutation in those genes have been removed, they've been buffered out. Now there's been a lot of speculation about why canalization might evolve, or whether it might just be a byproduct. And frankly in most cases we have no idea. This is an open research question.



So one of the reasons people think that say whole organism traits, like say five fingers or four limbs, might be buffered is not because of selection to buffer those traits but because there are very, very strong selection forces operating at the micro level within cells on gene signaling pathways. So you buffer those, and then as a byproduct of that you get buffering at a higher level. We don't know what's the case, but we do know that canalization exists and we do know it has a consequence; it allows hidden genetic variation to accumulate. So that's the fourth major reason why there can be neutral genes.



Now, what causes random or genetic drift? That will generate neutrality, but then what happens to the genes that are neutral? Well these are the mechanisms that can introduce randomness into evolution; most of them, there probably are a few others.



The first is mutation. The second is the Mendelian lottery, which is the idea that meiosis is like a fair coin. Then we have some population level effects. So mutation you can think of as a molecular event. The Mendelian lottery is a cellular event. Founder effects and genetic bottlenecks are population effects. And then we have a demographic effect, which is variation in reproductive success in a population of any size. All of these things contribute to random change. And now I want to step through them and give you a more concrete feel for how they work.



There are some senses in which mutation is not random. Okay? Mutations occur at some sites more frequently than others. In a pathogenic bacterium that is encountering a challenging environment, it will up its entire mutation rate by down-regulating its DNA repair. It's a fairly simple thing to increase the mutation rate on a whole genome. You just neglect to repair it and it will mutate faster. Okay? So if bacteria are moved into a new environment or, for example, if a pathogenic bacterium is put into a vertebrate with a very active and threatening immune system, it increases its mutation rate.



The transitions between the nucleotide classes--so purine to purine, pyrimidine to pyrimidine--are more frequent than transversions. So purines will mutate to purines more frequently than purines will mutate to pyrmidines.



And mutations do not produce random changes in phenotype space. This one again is a little bit abstract. Okay? But a mutation can only cause a change in the inherited set of possibilities. There is very, very little mutational variance in the human population for a sixth set of appendages, growing in the middle of our backs, that could be turned into the wings of angels; very little. Okay? There is very little mutational variance in a clam for any organ that could be involved in air breathing.



So mutations do not cover all of conceivable phenotypic space. Mutations are only causing perturbations in the inherited set of possibilities that a given evolutionary lineage has produced. So they're not making random changes in phenotype space. But they are random in an extremely important sense. There is no systematic relationship between the phenotypic effect of a mutation and the need of the organism in which it occurs. They're random with respect to fitness.



So when those bacteria are going into the vertebrate immune systems and it would be extremely convenient for them to have a mutation that was just exactly the right thing that they needed to avoid that particular defensive maneuver on the part of their host, they don't get it. Okay? All nature will give them is random mutations with respect to that particular function, and then if they have a lot of progeny, one of them may have the right one by luck.



Similarly, in your case, it might be extremely convenient for you to have an adaptation which allowed you to look at a computer screen for 48 hours without getting a headache and without having to get up to go to the bathroom. Okay? That mutation is not going to happen, because you need that function. Your genome is going to be covered by random mutations, and it may very well be that one of your children is able to look at that screen a little bit longer than you are. But that will be because it happened at random, not because somehow development or evolution could anticipate that that function was going to be useful.



So the process of mutation produces a lot of variation, and then natural selection edits it, it sorts it, it screens it. And at the point at which that variation is produced, the potential function of the variation is not a question, it's not an issue; it's just making variations.



Okay, second, meiosis is like a fair coin. So this is something that you may find boring. You've all heard about meiosis. You've all heard about Mendel's Laws. You know that the probability that a gamete will get into a particular--that a gene will get into a particular gamete is 50%. And you're all familiar with this because you know that the probability that a child will be a boy or a girl is 50%, and that's because at the sex chromosomes, and at all the other chromosomes that we have, the probability that the chromosome will go one way or the other is 50%.



That is absolutely amazing. Why is it that my Y chromosomes don't get 80% of the action? Why is it 50%? There's actually something very deep here. If you construct a system in which every one of the potentially competing elements has been forced to have the same chance, those elements must then cooperate, because the only way they can increase their own chances is by increasing everybody else's as well.



And that is why this particular effect is called the parliament of the genes. It is a discovery that Nature, about probably two billion years ago, hit upon a principle that human political science didn't discover until the Enlightenment, which is that democracies are stable. Meiosis is a democracy. In meiosis each gene has a fair chance, and that means that in a sense you've got a one-gene, one-vote situation.



So I'll come back--I'll come back to this fairness of meiotic segregation, but there's a general idea behind that. I've just given you a little scenario that would suggest why it was selected; it was selected to repress conflict. Every other aspect of genetics has evolved. So when you take genetics, or you take cell biology, or you take developmental biology, there were--there were selective processes that produce what you study, and there were alternatives that were rejected, and you're looking only at a sample of what nature can produce. And that in itself becomes an interesting research program.



Okay, back to the parliament of the genes. I referred to conflict. Here's the conflict. There are things called meiotic drivers. So there are genes which actually change Mendel's Laws; they change the probability that they will get into the next generation. Anybody already heard how a meiotic driver works? It's kind of a cool system. They use a long-range poison and a short-range antidote. So a meiotic driver usually operates by killing off any cell that does not have a copy of itself, of its gene, and giving an antidote to its own cell.



So as the cells sit there, in the ovary or in the testes or in whatever organ that particular organism has, the biotic drivers are basically wiping out the competition and promoting their own interests. These things are all over the place. They are common in drosophila, and there is evidence that there have been meiotic drivers in the human genome. Okay?



Once the diploid state evolved, there was a long history of invasion by meiotic drivers, and the response to that is that all the other genes wanted to cause these meiotic drivers to go away. They were distorting their own interests. You're sitting there on a chromosome, you're innocent. Some wild bandit comes along and highjacks your interests, and now your probability of getting into the next generation is only 20% rather than 50%. Who wants that, you know? That's not a good deal. So throughout the genome various mechanisms arose to repress meiotic drive; and the result was a very complicated mechanism and we call it meiosis.



So that's not the only possible reason for the complexity in fairness of meiosis. It is a plausible one. I invite you to consider the cultural evolution of democracy and decide whether it too might have been driven by a history of cheating, particularly the defection of leaders who no longer represented the interests of their people. I think there's a similarity, and I think you'll find it articulated in the Declaration of Independence.



Okay, mechanisms that cause random change also occur at the population level. One of them is the founder effect. Let's suppose that I were to found a new population with only you; it would have a high probability of blue eyes. And with you it would have a high probability of brown eyes. And in order to choose you I flipped a coin. Okay? At the founding of that population there was a random event, which was just sampling; just sampling a couple of individuals out of a big population.



And the result of this is that there are certain diseases, human genetic diseases, that are rare in the human population in general, but are common in populations that were founded by just a few people, including Tay-Sachs disease in Quebec, porphyria in the Afrikaners of the Cape, and diabetes in Pitcairn Island. So you just take a little sample out of a big population and you get something that's not representative, and sometimes that contains a genetic disease.



Another population level phenomenon that yields randomness is a bottleneck. So that will happen when a population crashes to a very, very small size, and then only a few alleles make it through. So you might have a lot of versions of a gene in a big population, but if you're only founding a new population with two or three individuals, they're--and they're diploid, well two individuals only carry four copies of the gene. So if there had been twenty alleles in the original population, the maximum possible number that could get through that bottleneck is only four; you've left behind sixteen.



It appears that this is what happened with the cheetahs. And they are apparently almost completely homozygous, particularly with respect to their immune genes. It is a weird biological fact that you can take a skin graft off of one cheetah and graft it to a cheetah, any other cheetah in the world, and the graft will take. In other words, their immune system finds a sample of skin from any other cheetah in the world to be their own skin. They don't detect a difference. And that probably is a signal that cheetahs went through a very small population bottleneck within the last few thousand years.



Genetic drift is then a consequence of neutrality. It's the random wandering of the frequencies of neutral genes. If you look through a microscope, Brownian motion is the jiggling of little dust particles that you see in the microscope, and it is actually the result of the random impacts of water molecules hitting that dust particle. Well the population level analog of heat in water is variation in population size--uh, excuse me, variation in family size. A gene which has gone through the Mendelian lottery of meiosis lands in a zygote. Okay? It got into the zygote. The zygote grows up.



This particular gene is neutral. It's not making any difference to reproductive success. But that particular individual that it landed in could have a small family or a big family, for reasons that have nothing to do with the function of the gene. It's just a flip of the coin that determines whether it will be in a family that produces two children, zero children, or a lot of children. Okay?



So that's what I mean by combining the lottery of meiosis with variation in reproductive success. And this is a process that goes on in all populations. When people are first learning about genetic drift, they think oh, that's something that happens in small populations, because small populations don't have all the smoothing effects of the Law of Large Numbers. But this will happen in a population of any size. Okay? And basically what I mean by that is this interesting consequence of variation in reproductive success. If it's correlated with a trait or with a gene, strongly, it produces natural selection. If it's not correlated it produces drift.



So one of the real puzzles of evolution has to do with what causes a gene to end up at random in an individual making one, two or three, or zero recruits per lifetime; what makes the difference between an adaptive and a neutral gene. I've sketched four possible answers to that question. In any particular case we normally do not know exactly which one is contributing the most to that.



So, what is it that happens to neutral alleles? [That's not going to work. I'll just have to draw over this.] If we draw time on the X-axis, and we draw frequency on the Y-axis, and a mutation occurs, the usual thing that will happen to a mutation is it will increase a little bit and disappear. Then we wait for awhile, another mutation occurs. We're looking, by the way, across many different genes in the population. We wait awhile, another mutation occurs. It comes into the population.



The probability that it will ever get fixed is pretty low because the probability is proportional to the frequency; excuse me, is proportional to 1/N, frequency equal to 1/N. When it's rare, its frequency is very low and so its probability of being fixed is low. But once in awhile a mutation comes along that manages to go through all of this drift, and making it through organisms that had, on average, more than two progeny per lifetime, and it gets fixed.



And if you just look at this class of mutations, the time that it takes them to fix is proportional to the population size. So things will get fixed faster in small populations than they will in big ones. There will be more of them, more mutations will occur in a big population, but it will take them longer to get fixed.



Now because the bigger populations have more mutations, it turns out that their size exactly compensates for the longer fixation times. So if you're just counting how many get fixed--it doesn't matter whether you're in a small population or a big one--the same number of mutations are getting fixed in both cases. That means that over the course of evolutionary history populations could've gone through crashes and explosions, and at the end of it, if you're a geneticist studying the DNA, looking back, it doesn't make any difference that the populations had crashes and explosions, in terms of how many neutral alleles got fixed. They were just getting steadily fixed, with no effect of population size.



So we don't know which one will be fixed. We do know how many will be fixed. So this is why the molecular clock is like an atomic clock; it's driven by radioactive decay. We don't know how many atoms--we don't know which atom will decay, but in a second we know how many will, for a given radioactive substance.



The reason for this is that there's regularity in large numbers. It emerges because there are a large number of independent events. Our haploid genome has about three billion base pairs. One mole of uranium has about 6 times 1023 atoms--actually if it's a mole it has exactly that many atoms--and these large numbers give the regularity to the process.



Okay, so this is what connects microevolution to macroevolution. It creates uniform substitution rates in neutral portions of the genome. And this is the assumption that molecular evolution makes when it reconstructs the Tree of Life. It allows us to estimate branch lengths and branch points to last common ancestors. It allows us to make comparative inferences on phylogenetic trees. And therefore neutral evolution is a actually a central tool in the construction of the evolutionary framework. It's not something to be neglected; it's something to be understood, because it gives us a source of regularity that can take us back into deep time.



As an example, here are nucleotide substitutions occurring in flu. These are isolates that are still in the freezer. Okay? And they run here from about 1925 up to 1990. We don't have any, any error of estimate in age; we know when they were isolated. Okay? The population sizes have fluctuated dramatically. At some point, some of these flu strains were sitting in a few ducks or pigs in southeastern China. At other points, they were inhabiting a billion people around the world. They went through huge fluctuations, and a nice steady rate of substitution. Okay?



All the mechanisms of genetic drift are in play here, except meiosis, because flu is a virus, doesn't go through meiosis. The effect of variation in population size was exactly compensated by the much slower rate of fixation of neutral mutations in larger populations. So even in an epidemic disease, like flu, the molecular clock is nice and steady.



A few caveats about that. Different proteins and different parts of proteins evolve at different rates. They only use non-transcribed DNA sequences. There are some differences among lineages because of different generation times.



And I'm not going to talk about maladaptation because I took too long to talk about neutrality. So you can read about maladaptation, and I'll just give you the basic idea. Here's the basic idea of maladaptation. If natural selection is strong in one place and organisms get really well adapted to it, but they move to another place, where they don't do well, for whatever reason, we call the place that is producing an excess of organisms the source, and the place which is not good for the organisms a sink. The genes in the sink represent organisms usually that were adapted to the source. So if organisms get well adapted in one place and moved to another that's quite different, and they never get an opportunity to come into evolutionary equilibrium with that new place, which we call the sink, then they are maladapted to the sink. That is the basic idea behind how maladaptation can occur. Okay?



So, let me jump ahead. I will just run quickly through these examples and get to the end, just to let you know what happens next time. These are the keys I want you to remember. I want you to remember how it is that meiosis is like a fair coin. I want you to remember how the fixation of a neutral allele is like radioactive decay. And I want you to remember that the regular fixation of neutral alleles generates a molecular clock that allows us to connect micro to macroevolution. Okay, that's it.



[end of transcript]

Genetics controls evolution. There are four major genetic systems, which are combinations of sexual/asexual and haploid/diploid. In all genetic systems, adaptive genetic change tends to start out slow, accelerate in the middle, and occur slowly at the end. Asexual haploids can change the fastest, while sexual diploids usually change the slowest. Gene frequencies in large populations only change if the population undergoes selection.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 4

Transcript



January 23, 2009



Professor Stephen Stearns: Today we're going to talk about Adaptive Genetic Change. And in order to set the stage for this, before I get into the slides, I would like you to consider the following proposition. Every evolutionary change on the planet, that has ever led to something that you think is cool and interesting and is well designed, whether it is the brain of a bat, or the vertebrate immune system, or the beautiful structure of the ribosome, or the precision of meiosis, has occurred through a process of adaptive genetic change. A mutation has occurred that had an effect on a process or a structure and, if it increased the reproductive success of the organism that it was in, it was retained by evolution; and if it did not, it disappeared.



So what we're talking about today is a look into a very basic mechanism that is operating in all of life and is causing the accumulation of information. Now, these are the keys to the lecture. In the middle of the lecture you're going to get a couple of slides that have tables and equations on them and stuff like that, and I'll lead you through one of those tables, and I'll ask you to go through another one. But they're not the point. The point is this. There are four major genetic systems, and there are some interesting exceptions to them. But you can capture a big chunk of the variation in the genetics of the organisms on the planet with just four systems. Okay?



They are sexual versus asexual and haploid versus diploid, and those differences make a big difference to how fast evolution occurs. You guys are sexual diploids and you evolve slowly, and your pathogens are asexual haploids and they evolve fast. That's important, the kind of thing you ought to know.



Now when we get into the equations of population genetics--they're just algebra--the point is that you can always go find them in a book and you can program them pretty easily, even in simple spreadsheet programs like Excel, and you can understand their basic properties by playing around with them. If you go on the web and go to Google and type Hardy-Weinberg equations, you're going to get 20 websites around the country where some professor of population genetics has put up some package for students to play with and it's going to generate all kinds of beautiful pictures and stuff like that.



It's real easy for you to lay your hands on these tools now. What's important for you to know is (a) that they are there and represent something important; (b) what their major consequences are; and (c) how to get a hold of them when you need them. I am not going to ask you to repeat the derivation of the Hardy-Weinberg equations on a mid-term. Okay? But I do expect you to know why they're important and what they're about.



The third thing that I want you to take home from this lecture is that when adaptive genetic change starts to occur, it is virtually always slow at the beginning, fast in the middle and slow at the end. So that if you are looking at a graph of gene frequencies over time, it looks like an S; and that's the third thing. That's it, there's the lecture, ta-da. Now background to this decision.



When, in 1993, Rolf Hoekstra and I began to put together the first edition of this book, I asked Rolf to be my co-author because he is a population geneticist. He has a marvelously clear mind. He likes those kinds of equations and he's really good at them. And we, Rolf and I, went around and we asked about fifteen of the leading evolutionary biologists in the world, "What's important? What should every biologist know about evolution? This is for everybody. This is for doctors and molecular biologists and developmental biologists, everybody. What should they know?" And I said, "Rolf, your job is to figure out the part from population genetics." And he came back, after about two weeks, and he said, "You know Steve, I don't think there is anything."



I was shocked. I said, "Rolf, you're a population geneticist. This stuff is important, right?" And then he said, "You know, the way we normally teach population genetics, which is as a big bunch of equations that are about drift and frequency change under selection and so forth, most people end up not really needing that. What they need to know is that there are four main genetic systems and that genetic change is slow, fast, slow."



So that's where this lecture came from. It came from somebody thinking deeply about that, and asking lots of people. Now if you like this, there's a whole field there, there's a whole bunch of wonderful stuff that you can do. But these are the things that everybody I think should know.



So here's the outline. I'm going to give you the context, the historical context that led to the concentration on genetics in evolutionary biology. I'll talk a little about the main genetic systems. Then I'll run through changes in gene frequencies under selection and, if I have time, I'll get to selection on quantitative traits. If I don't get to selection on quantitative traits, it will be because I have engaged in a dialog with you about some interesting puzzles, and that dialog is more important to me than getting to quantitative genetics. Okay?



So here's how genetics became a key element in evolutionary thought. Darwin did not have a plausible genetic mechanism and he failed to read Mendel's paper, which came out six years after he wrote The Origin, but before he constructed some of the later editions of his book, and so he reacted by incorporating elements of Lamarck into his later editions. If you read the Sixth Edition of The Origin of Species, it's got some really Lamarckian statements in it, inheritance of acquired characteristics.



Anybody here know what the problem was with Darwin's original model? Anybody know how Darwin thought genetics worked in 1859? He had a model of blending inheritance. That meant that he thought that when the gametes were formed, gemmules from all over the body, that had been out there soaking up information about the environment, swam down into the gametes, into the gonads, carrying with them information about the environment into the gametes, and that then when the zygote was formed, that the information from the mother and the information from the father blended together like two liquids.



In other words, he didn't think of genes as distinct material particles. He thought of them as fluids. Now if I give you a glass of red wine and a glass of white wine, and I pour them together, I get pink wine. And if I take that glass of pink wine and I pour it together with another glass of white wine, I get even lighter pink. And you can see that if I continue this, pretty soon red disappears completely. The problem with blending inheritance is that the parental condition gets blended out and there isn't really a preservation of information.



That's why Darwin came under attack. And Mendel wasn't known, and he resorted to Lamarckianism, and he was wrong. So genetics became an issue. In the year 1900 there was a simultaneous rediscovery of Mendel's Laws, and at that point people went back and they read Mendel's paper, and they realized that they had missed this 35 years earlier.



Then the so-called 'fly group' of Thomas Hunt Morgan and Sturtevant and Bridges, who were working at Cal-Tech, demonstrated that genes are carried on chromosomes. And enough then was known about cytology, so that we knew that chromosomes had an elaborate kind of behavior, at mitosis and meiosis, and people then, about 1915, showed that in fact the behavior of chromosomes was consistent with Mendel's Laws. They didn't know at that point what chromosomes were made out of. They had no notion of the genetic code, but they could establish experimentally that genes were on chromosomes; and that was done by 1915.



However, there were still issues about whether all of this would actually work at the population level. It was not immediately clear that you could take Mendelian genetics and then construct populations out of it, that obeyed Mendel's Laws, and have natural selection work. To do that actually required a fair amount of math, and the people who did it were Ronald Fisher, J.B.S. Haldane and Sewall Wright, and they did it between about 1918 and 1932.



In so doing, they also invented much of what is now regarded as basic statistics. So Fisher had to invent analysis of variance in order to understand quantitative genetics, and Wright had to invent path coefficients in order to understand how pedigrees translate into patterns of inheritance. So these guys laid the foundations.



As a result of that, genetics really became regarded as kind of the core of evolutionary biology during the twentieth century, and there's been a tremendous concentration on it. And it is still true that many people will not accept a claim about any evolutionary process unless it can be shown to be consistent with genetics. That's sort of a Gold Standard. If you can't do it genetically, if you can demonstrate it's genetically illogical, then a claim just falls theoretically; you don't even have to go out and get the data. Therefore, of course, the Young Turks have great joy in discovering cases that don't fit and come up with epigenetics and lots of stuff like that. At any rate, that's ahead of you; that's not today.



The genetic system of a species is really the basic determinant of its rate of change. So we have sexual versus asexual species--there are complications to this--and we have haploid versus diploid, and there are other ploidy levels. Can anybody name me asexual vertebrates; not sexual vertebrates but asexual vertebrates? Anybody ever heard of an asexual vertebrate? Fish, amphibians, reptiles, birds, mammals?



Student: Wasn't there a recent documentation of a shark? You mentioned it.



Professor Stephen Stearns: I could imagine that a shark might be capable of being asexual. I haven't heard of that case.



Student: I think it was kind of a [inaudible]



Professor Stephen Stearns: Yes, there are some. There are some asexual lizards. There are some interestingly asexual fish. There are some frogs that manage to be kind of quasi-asexual by using male sperm but then not incorporating it into gametes--excuse me, in the developing baby. So they use it just to stimulate development. There's one case in captivity of an asexual turkey.



But asexual types are not frequent among vertebrates. They are common in plants. Of course, most bacterial sex is asexual, although bacteria do have a bit of sex. You're diploid; your adult large form is diploid. Anybody know what group of plants is haploid in the state in which you normally see them in nature, where the big recognizable thing is haploid? I'll show you one in a minute. I just wanted to check. Mosses; mosses are haploid. Okay, so this is what's going on with these four systems.



Basically the difference between sexual haploids and sexual diploids is the point in the lifecycle where meiosis occurs. If the adult is diploid and meiosis occurs in gonads in the adults that produce gametes, and then the zygote form develops so that all of the cells in the developing organism are diploid, you get the diploid cycle. If you have the zygote having meiosis immediately, or shortly after being formed, so that the developing young are haploid, then you get a haploid adult. So this is what moss do and this is what we do. Then we have asexual haploids and asexual diploids, and at least in outline they look pretty simple. Asexual diploid, just makes a copy of itself; just goes through mitosis, makes babies. Asexual haploid, same kind of thing.



So those are the four major genetic systems. There are many, many variations on them. So the asexual haploids are things like the tuberculosis pathogen, blue-green algae, the bread mould, the penicillin fungus, cellular slime moulds, and they constitute the bulk of the organisms on the planet.



Sexual haploids are things like moss, and red algae; most fungi are sexual haploids. In this case you can see that's where the haploid adult is in the lifecycle. There are where the gametes are formed. They are formed up on the head of the adult. You can see the pink and the blue are coding for the male and the female gametes, on different parts of the gametophyte. Then the zygote forms where the sperm gets into an ovule, on the tip of the plant, and then the young actually develop up here. So this is haploid up here and then the spores go out--meiosis has occurred in here and the spores go out as haploid spores. So that is a sexual haploid lifecycle.



The asexual diploids include the dynoflagelates; there are about ten groups of the protoctists--that's the modern name for what you think of as protozoa, but it also includes some single-celled organisms that have chloroplasts in them--the unicellular algae, some protozoa, some unicellular fungi. There are a lot of multi-cellular animals that are asexual diploids, and this one here, the bdelloid rotifer is one of them. It is called a scandalous ancient asexual. Anybody know why the word 'scandalous' is used in this context? Yes? What?



Student: No males.



Professor Stephen Stearns: There are no males; bdelloid rotifers do not have any males, nobody's ever seen a male bdelloid rotifer. But that's not the scandal; I mean, if you're a male you might think it was scandalous. Right? [Laughter] But for an evolutionary biologist, no, that's not scandalous.



Well it actually has to do with this part of it right here. Almost all asexual organisms on the planet, that are multi-cellular--leaving out the bacteria--but all the multi-cellular ones are derived from sexual ancestors and originated relatively recently, with a few exceptions, and this is one of the exceptions. There is a whole huge body of literature on the evolution of sex that says one of the things that sex is good for is that it allows long persistence.



We see that sexual things have been in a sexual state on the Tree of Life for a long time, and the asexual things have branched off of it, and we don't see very many ancient ones. The reason for that--we'll come to that, when we get to the evolution of sex--is that both because of mutations and because of pathogens, sex repairs damage and defends the organism against attack. So this is a low maintenance, poorly defended organism, and it looks like it's been around without sex for perhaps 300 million years. The scandal is we don't know how it did it. Okay? That's why it's called a scandalous ancient asexual. Yes, that's a very intellectual definition of scandal; I agree.



Okay, sexual diploids. You guys are sexual diploids, this bee is a sexual diploid, and that flower is a sexual diploid. They have this kind of lifecycle, as is sketched here, the one that I talked about earlier. So about twenty animal phyla are sexual diploids. Many plants, most multi-cellular plants are, and there are some algae protozoa and fungi that are sexual diploids. They include the malaria and sleeping sickness pathogens. There are some things that don't fit; the sexual diploid part doesn't fit, for malaria and sleeping sickness.



The things that are alternating between being haploid and diploid, with neither one dominating, are mushrooms, microsporidian parasites, which are things that are actually quite common in many insects, and the malaria--malaria has a very complex lifecycle. So it is haploid inside your red blood cells, it's diploid at a certain point in a mosquito, and it's moving back and forth.



The things that alternate sexual and asexual reproduction: there are some rotifers, some cnidarians, some water fleas, some annelids. There's a great little annelid that lives in the bottom of the Harbor of Naples in Italy, and it actually does everything. It can be asexual--the same species--it can be asexual; it can be born as a female and turn into a male; it can be born as a male and turn into a female; and it can be born as both and do both. So some things are really flexible, but most things aren't. And the timing of sexuality and asexuality is an important part of the lifecycle of all of these things.



Last fall, for example, there were huge jellyfish blooms over much of the world's oceans, and that's part of a complex lifecycle in which there is an asexual phase on the floor of the ocean, that builds up what looks like a stack of dinner plates, and then the top plate flips off and turns into a jellyfish. It goes off as a jellyfish and has sex and makes larvae, and then goes down and turns into an asexual thing on the bottom that makes stacks of dinner plates. So there's a lot of variety out there. All of these things probably evolved from an asexual haploid; and we say that because we believe that the bacterial state was the ancestral condition.



Okay, now genetics constrains evolution, and genetics is doing something to evolutionary thought which is about what chemistry does to metabolism and structure, and is about what physics does to chemistry. Okay? There's a broad analogy there. If you want to understand molecular and cell biology, you learn a lot of chemistry. If you want to understand some evolution, then you need to learn a little bit about how genetics constrains evolution, and so you need a little math. So I'm going to give you some simple math, and here's some terminology to soak up.



So we're going to represent these ideas by symbols. We're going to call alleles Aa. So those are two alleles at one locus; a little exercise of genetic terminology. We're going to let p be the frequency of A1, and q the frequency of A2. And frequency just means the following: some traits are Mendelian, which means that they're easily recognized in the phenotype.



One of the Mendelian traits in humans is the ability to curl your tongue. I am a tongue curler. Okay? How many of you can curl your tongues? Okay, let's say it's about 45. How many of you cannot curl your tongues? Let's say it's about 30. So the frequency of tongue curling is going to be--I'm just making up the numbers, right?--45 divided by 75. That's how we get the number. And by the way, the frequency of the other one is going to be 1 minus that frequency, because p plus q is equal to 1; and we'll let s be the selection coefficient, which is measuring the reproductive success of the organism carrying this trait, the difference that it makes.



And if we look at the genetic change in asexual haploids, basically what one does is make a table of the process; and it is moving from young, in the present generation, through the adult stage, to young in the next generation. So we try to go through one generation. This is an active Cartesian reduction. We're taking a complex process and breaking it down into the parts that are essential for the thing that we're thinking about.



We have genotype frequencies--for genotypes A1 and A2 they're p and q--and we have relative fitnesses up here. The only place that selection is making any difference, on this whole page that's in front of you, is right here. And basically what--our placing that there is an act that means the following. We are only going to think about the case in which there is some difference in the juvenile survival of A2; it's different from A1. If it makes it to adulthood, there's no difference; we don't put that down in the table. So this is a case where we're just--you know, it's a special case--we're just looking at the juvenile survival difference between A1 and A2. What happens?



Well it changes the frequencies of A1 and A2 in the adults. Basically it changes them by reducing the number of A2s. Some of them have died out; that's 1 minus s, that's what the 1 minus s is doing. You can take these expressions here and you can simplify them so they look like this--it's just a little bit of algebra--and because these are the frequencies in the adults, the young in the next generation have exactly those frequencies, because there is no selective difference in the adult stage. Okay? That's what that table means.



Now a little bit about this. This little process that I've gone through, which probably looks like remarkably simplistic bookkeeping to you, is actually the part of doing applied mathematics which is the most difficult. It is the translation of a process into something analytically simple, that you can deal with. In the act of doing it, you make certain assumptions to simplify the situation, and by writing them down it helps you to remember what assumptions you made and what thing you're actually looking at.



We're not looking at all of evolution here, we're looking at a very special case; we're looking at asexual haploids where selective differences only occur in juveniles. What happens is you get a change in the gene frequencies of the adults that result from that process, and then that exact change is passed on to the next generation. So that's the part of this process that I want you to remember. You can go look this stuff up any time. You don't need to memorize that. You can program this as recursion equations and apply them repeatedly. Okay?



Now let's do it for sexual diploids. In the sexual diploids, you've already been exposed to the Hardy-Weinberg Law, this p2 2pq q2 law. In order to get it, we have to assume random mating in a big population. The reason you need the big population is so that those p's and q's are actually accurate measures. In a small population they're noisy, but in a big population they are good stable estimates. And if there's random mating, that means that matings are occurring in proportion to the frequency of each type.



So you get a Punnet diagram like this. You have the probability of one of these alleles occurring; and one parent is going to p, the other allele in that parent q. Same for the other parent. These are the possible zygotes that will result from that. This one has probability p2; this one has probability q2; and these two together have probability 2pq. That's just simple basic probability theory.



Now, the important thing about the Hardy-Weinberg Law is that it implies that there's no change from one generation to the next. The gene frequencies under Hardy-Weinberg don't change. That means that the information that's been accumulated on what works in the population doesn't change for random reasons. If it's going to change, it's going to change because that big population is going to come under selection. Okay?



That means that replication is accurate and fair, at the level of the population, just as it is at the level of the cell. Now, of course, gene drift is going on, but we're not so worried here about gene drift, because gene drift is affecting things that aren't making a difference to selection, and we're building models of selection. What Hardy-Weinberg does is tell you if there isn't any drift, if there isn't any mutation, if there isn't any selection, if there isn't any migration in the population, and if you don't have a high mutation rate, things are going to stay the same. So if they're changing, one of those things is making a difference. Okay? And that gives us a baseline.



So it gives us a baseline to see the process of selection occurring, but it also means that random mating in large populations preserves information on what worked in the past. So you don't have to invent everything all over again. And a note for future lectures, these are also the conditions that remove conflict by guaranteeing fairness. So basically the Hardy-Weinberg situation is one in which everything that was in the population last generation has exactly the same chance of getting into the next generation, in proportion to its frequency; nothing is going to change.



Okay, here's a genetic counseling problem, and I'm going to take a little time on this. We go back to John and Jill. They've fallen in love, they want to get married, but they're worried. John's brother died of a genetic disease, and that is a nasty one. It's recessive, it's lethal, it kills anybody that carries it before they can reproduce. That's fact one. Jill doesn't have any special history of this disease in her family, but that history's not well known, and so we estimate the probability that Jill carries the disease from the frequency of deaths in the general population, and that frequency is 1%; to make it easier for you to calculate. Okay?



What's the probability that they will have a child that dies from this disease in childhood? The probability is .03. Your problem is not to tell me .03, your problem is to tell me why did I use that equation? Okay? So take a look at that equation for a minute, take a look at that problem, and let's go through and pull it apart. Can anybody see why either the two-thirds or the one-quarter is in the equation?



Student: We know that his brother has a recessive version of the lethal gene, and therefore John is either heterozygous--doesn't look like it's dominant, looks like it's recessive. So if he is heterozygous or homozygous recessive, then he's carrying the gene; which is what we're worried about. So there's a two-thirds chance that he is either carrying it or actually has the disease.



Professor Stephen Stearns: That's correct. The only slip you made in expressing that is that we know that if they are going to have a child that has the defect, they both must be heterozygous, and so we're concentrating specifically on what's the probability that they're heterozygous. You then gave me that probability. Does anybody have a problem seeing why the probability that John is a heterozygote is two-thirds, rather than 50%; excuse me, that the baby is a heterozygote is two-thirds? Yes?



Student: So we're going to keep him as a [inaudible].



Professor Stephen Stearns: Yes, you do. Okay. This is for the baby. Okay? If John is a heterozygote and if Jill is a heterozygote, they can have either a homozygous recessive, and that one will die before birth; they can have a homozygous dominant, perfectly healthy; or they can have a heterozygote. The probability of the homozygote recessive is 25%, the probability of the homozygous dominant is 25%, and the probability of the heterozygote is 50%.



But, the probability that John and Jill will have a baby that dies from this disease in childhood is going to be therefore this one-quarter. This two-thirds is going to be the probability that John is a heterozygote. How do we know that John--John's parents were both heterozygotes?



Student: They had a recessive son.



Professor Stephen Stearns: They had a recessive son. John's parents had to be heterozygotes. Therefore, given that John's parents were heterozygotes, his probability is two-thirds. We know he survived to adulthood; the other 25% died. So of those who survived to adulthood, two-thirds are heterozygotes and one-third are homozygotes.



Student: Why can't one be homozygote recessive and the other one be heterozygous? [Inaudible].



Professor Stephen Stearns: Because if one, the parent--if one parent was a homozygote, it could only have been homozygous dominant, because it survived to adulthood, to have a child. And if the other parent was a heterozygote, the only possibilities for the children are both heterozygotes; and that wasn't the case, because John's brother died. Okay? So this is the probability that John is a heterozygote. This is the probability that if John and Jill have a baby, it will have the problem. What's this thing in the middle--2 times 0.9 times 0.1?



Student: [Inaudible]



Professor Stephen Stearns: Right. That's the probability that Jill is a heterozygote, and we get that from here. The square root of 1% is .1. 1 minus .1 is .9. This is q and this is p and this is 2pq. Okay? Where did we get this from? That's in Jill's part of the population. Those are the baby--oh you've got it.



Student: The probability has to be out of the entire population, and the long-term population, they can't reproduce--[inaudible].



Professor Stephen Stearns: Right. So we have to correct the percentages for the ones that have died. Yes, you got it. Do you see how much goes into dissecting an equation like that? But because we've set up the logical apparatus, we can go through a sequence of steps and say, "Okay, first we know they both have to be heterozygous. Then, if they are both heterozygous, the probability that Jack is, is two-thirds; the probability that Jill is, is 2pq, corrected for the fact that 1% have died. She has survived, so we have to correct for that. Then this is the probability that their baby has the disease." That's the kind of process that one goes through when thinking about population genetics.



This is the table for sexual diploids that reflects this kind of thinking. It is more complicated because now we have to keep track of both the haploid and the diploid condition. So we have these haploid gametes, with frequencies p and q. We have the diploid zygotes. Then another process comes in.



We can have a selective difference--I made a +S here; I made a -S in the last one. I made that change deliberately, just so that you'd see it as arbitrary; because we can make S negative or positive itself. Right? S doesn't have to be a positive number; neither does H. Anybody have an idea what H might be in there for? It's in there to represent something that's going on in genetics. Yes?



Student: Is it heritability?



Professor Stephen Stearns: No it's not heritability, in this context. Okay? Yes?



Student: Is it the Marsh's coefficient for being heterozygous? [Inaudible]



Professor Stephen Stearns: Not in this context. Good idea, but no. What is it about that heterozygote that doesn't necessarily have anything to do with selection? H expresses dominance. It expresses the degree to which A1 is covering up A2 in the phenotype.



Dominance itself is not something that's always there. If there isn't any dominance, then the heterozygote is just exactly halfway in the phenotype between the two homozygotes. So H is a little mathematical symbol that allows us to deal with situations in which either there's a lot of dominance or none at all. If H = 0, there's no dominance. Okay? No excuse me, the way it's set up, if H = 0, then A1, A2 is just exactly like A1, A1, and there is dominance. So we have to make H something non-zero, in order to express deviations from dominance, the way this one is set up.



At any rate, the--what's going on here is essentially the same kind of selection process. There is a selective difference, which is disadvantaging A2. So A2 doesn't survive as well as A1. When it is in the heterozygous form, it may do better, if there's some dominance. And that results in a more complicated set of equations.



W here is defined as this big term. We have basically the adults being p2, 2 pq times 1 plus hs. And A2, A2 has a frequency of q2 times 1 plus s, which is the selection coefficient over here. So q is changing the most, and to the degree that A2 can be seen in the heterozygote, it will also be affected by s, but it won't be affected if there is complete dominance. Okay? So if h is zero, there's no effect of selection on the heterozygote; this term cancels out. The result of that is that you get these frequencies forming the next generations.



Now there a couple of ways of setting up this whole derivation, and in the Second Edition of the book, Box 4.1 and Box 4.2 do it a little bit differently. You might want to just step through those things in section. The goal here is not to memorize how to derive the equations, or to memorize the equations. Because, as I've said, you can always pick them up in a book, or pull them off the web, and you can find programs that will do it all the time. The goal is to understand what it is that population geneticists are thinking about when they set it up this way, and what power it gives them.



So let me just show you what happens when you program these recursion equations. By the way, they're called recursion equations because they give us the frequency in the next generation as a function of the frequency in this generation. So they form kind of a Markov chain. They allow us to calculate next time from this time; that's something computers are really good at.



So this is the take-home message of all that analysis: you look at genetic change, in asexual haploids, sexual diploids, and it's slow at the beginning, fast in the middle; it's slow at the end. The haploids change faster than the diploids, and the dominants change faster than the recessives. So let's step through that and see if you can tell me why this is the case.



First let's take the asexual haploids, or haploids of any kind. Why is it that haploids change gene frequencies faster, for given selection pressures, than do diploids? Yes?



Student: The entire gene--all the genes are inherited. It's not all [inaudible]; it's sort of a complete replication of them, the order.



Professor Stephen Stearns: Well that is what a haploid is, but that doesn't explain why it's faster. The statement is true, but it's not an answer to my question. Another try. Yes?



Student: Well all the [inaudible], the bad genes die off. [Inaudible]



Professor Stephen Stearns: Okay, that's going in the right direction, but I think it can be expressed even more clearly. Yes?



Student: [Inaudible]



Professor Stephen Stearns: That's interesting. That actually gets into the evolution of sex. I'm actually thinking though about an answer that has more to do with developmental biology and not so much to do with sex, at this point. Um, actually I think that, uh, your answer is partially correct, but it's more complicated than what I was looking for. [Laughs] Yes?



Student: Is it that all asexuals can reproduce?



Professor Stephen Stearns: No, it's not that all of the asexuals can reproduce. Many of them die as juveniles. It has to do with haploidy versus diploidy. Yes?



Student: Then if the organism has the allele that's different, it's going to best.



Professor Stephen Stearns: Yes.



Student: And that's when this other comes along.



Professor Stephen Stearns: Every gene is expressed, and there's no dominance covering up any hidden genetic information. The genes are exposed to selection, in haploids. Yes?



Student: So why is that faster than a dominant zygote, [inaudible]?



Professor Stephen Stearns: Good. We'll find out as we go through the next questions. Okay? So the haploids are faster than a dominant diploid because--?



Student: [Inaudible]. That's why it's a recessive gene.



Professor Stephen Stearns: Basically, yes. The heterozygotes react like the dominant, but contain the recessive. And so if you're measuring the rate of evolution as the rate at which the dominant takes over the population, it's carrying along in the heterozygotes a bunch of recessives. Okay? They're doing just as well as it is. So development, which is covering up the difference between the two, is actually giving the recessives an advantage and slowing down the rate at which the dominant can take over. Okay?



Recessive diploid; I think that you now see why that would be the slowest. If we have an advantageous recessive gene, it gets slowed down by the fact that when it's in the heterozygote, its effects are being covered up by the other allele. Okay, why is it S-shaped? Why is the trait--let's do it for a dominant diploid sexual. Okay? Slow at the beginning, fast in the middle, really slow at the end. Let's concentrate on first why this is really slow at the end, and then we can also look at why a recessive diploid sexual is really slow at the beginning.



What do you have to think about in order to pull the answer out of that diagram? What proportion of the population is in heterozygous form, as you get near the end? If you're a dominant diploid sexual and you're at a frequency of .9, 81% of you are going to be dominant homozygotes; 18% of you are going to be heterozygotes; and 1% of you are going to be recessive. There are eighteen times as many heterozygotes as there are recessive homozygotes. Selection, at that point, is trying to eliminate that 1% of recessive homozygotes. It can't touch the 18%.



If you carry that process over, where we're dealing with .01 and .99, it gets even more extreme. A tinier and tinier fraction of that population is a recessive homozygote. A larger and larger fraction of the remaining recessive alleles are tied up in heterozygotes, where selection can't operate. So this thing just slows way down. It gets harder and harder to get rid of the disadvantageous alleles, because a larger and larger proportion of them--not an absolute number but a larger proportion of them--are hidden in the heterozygotes.



The same thinking describes why evolutionary change in a recessive diploid, where the recessive gene has the advantage, is very slow at the beginning. If a new recessive mutation comes into the population, it's a very low frequency. Its frequency is 1 divided by the number of individuals in the population. The only things it can mate with are dominant forms. All of its babies are heterozygotes.



So at the beginning selection can't operate on it at all. Only after two heterozygotes manage to get together and mate, which means they must have come to fairly high frequency, will they have a baby that is a recessive homozygote that selection will operate on. So it takes awhile to get this going. And because of dominance, it takes a long time to build up to the point where it accelerates. But then at the end it's fast, because at the end the thing that's being selected is the recessive, and it speeds up as it goes through.



Okay, I thought this would happen, uh, it's time for class to end, and I'm just getting to quantitative genetics, and so I'm going to let you pick up quantitative genetics from the lecture notes and from the reading. I do want to indicate as potential paper topics though that quantitative genetics has got some of the most interesting questions that we encounter in evolutionary biology, and that it includes questions like the heritability of intelligence, the heritability of SAT scores--those are all things where the apparatus you need to analyze the issue is given to you by quantitative genetics.



And there is a good paper on this, and I have put it up on the course website, under Recommended Readings; there's now a folder called Recommended Readings, PDFs of Recommended Readings. You can find this paper and some other ones in there, if that's something that strikes your fancy. Go take a look at the title and abstract. So this is the summary of today's lecture. And the next time we're going to talk about the origin and the maintenance of genetic variation.



[end of transcript]

Mutations are the origin of genetic diversity. Mutations introduce new traits, while selection eliminates most of the reproductively unsuccessful traits. Sexual recombination of alleles can also account for much of the genetic diversity in sexual species. In some instances, population size can affect diversity and rates of evolution and fixation, but in other cases population size does not matter.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 5

Transcript



January 26, 2009



Professor Stephen Stearns: Okay, today we're going to talk about the origin and maintenance of genetic variations; and this is continuing our discussion of central themes in the mechanisms of microevolution. The reason we're interested in this is that there cannot be a response to natural selection, and there cannot be any history recorded by drift, unless there's genetic variation in the population. So we need to understand where it, where it, comes from, and whether or not it sticks around.



If it happened to be the case that every time a new mutation popped up it was immediately eliminated, either for reasons that were random or selective, evolution couldn't occur. If a lot of variation came into the population, and then persisted for a tremendously long time without any sorting, we would see patterns on the face of the earth that are totally different from what we see today. So these issues are actually central issues in the basic part of evolutionary genetics that makes a difference to evolution.



So the context basically is this. Since evolution is based on genetic change, we need to know where genetic differences come from; and the rate of evolution depends on the amount of genetic variation that's available in the population, so we need to know what maintains the variation. If you were to go back fifty, sixty years, which is what we now think of as the classical view--remember the classical view is a moving window in time--at that point it was thought there wasn't very much genetic variation out there and that evolution was actually limited by the rate at which genetic variation was created.



Since 1965, with the discovery of protein isozymes, and especially now, since the discovery of ways to sequence DNA very cheaply, we know that's not true. There is a tremendous amount of genetic variation in Nature, and I'm going to show you some of it this morning. So since about 1975, 1980, due to a series of studies, some of them on the Galapagos finches, some of them on the guppies in Trinidad, some of them on mosquitofish in Hawaii, some of them on the world's fish populations responding to being fished, we know that evolution can be very fast when there's strong selection acting on large populations that have lots of genetic variation.



So really the rate of evolution--and, for example, the issue of climate change and global warming--will all the species on earth be able to adapt fast enough to get--to persist in the face of anthropogenic change on the planet?--that issue is directly addressed by the things we're talking about this morning.



If there isn't enough genetic change to adapt, say, the grassland populations of the world, or things that are living on mountains, to the kinds of climatic changes that they are going to be encountering, and currently are encountering, they'll go extinct. Ei--they have to either move to a place which is like the one they're in, or they have to adapt to the changed conditions that they're encountering.



So the outline of the lecture today basically is this. Mutations are the ultimate origin of all genetic variation. Recombination has a huge impact on variation. So what that means basically is that sexual populations have the potential to be much more variable than asexual populations--there is lots of genetic variation in natural populations. And then we will run through four mechanisms that can maintain variations in single genes, and briefly mention the maintenance of variation in quantitative traits.



So mutations are where these genetic differences come from, and they can be changes in the DNA sequence or changes in the chromosomes, and in the chromosomes they can be changes in how many chromosomes there are in the form of chromosomes or in aspects of chromosome structure. So there can be gene duplications and so forth. Most of the mutations that occur naturally are mutations that are occurring during DNA replication.



For those of you who are thinking of being doctors, this is important because the probability that a cancer will emerge in a tissue is directly proportional to the number of times cells divide in that tissue; which is why cancers of epithelial cells are much more common than cancers of cells that do not divide. You never get a cancer in your heart muscle, and you frequently get cancers on your skin, and in your lungs, and in the lining of your gut, and that's because every mitotic event is a potential mutation event.



The kinds of DNA sequence mutations are point mutations; there can be duplications, and in the chromosomes as well there can be inversions and transplacements that go on. Genes can be moved around from one chromosome to another. They can actually be turned around so that they are in the opposite reading direction, along the chromosome. All those things are going on.



There's good reason to think that an intermediate mutation rate is optimal. If the mutation rate is too low, then the descendants of that gene cannot adapt to changed conditions. If it's too high, then all the accumulation of information on what has worked in the past will be destroyed by mutation; which is what happens to pseudogenes that are not expressed. So some intermediate rate is probably optimal.



Now a gene that controls the mutation rate will evolve much more easily in an asexual organism than in a sexual species because sexual recombination uncouples the gene for the benefits of the process. Let me illustrate that.



Suppose that I am engaged in a process that Greg wants to control, and we've got a certain period of time we can do it in, and so he decides that he's going to do it, with me, on a bus going to New York. We go down to the bus station and, because of recombination, he gets into one bus and I get into another. He loses his opportunity to control me, simply because I am now riding in a different bus.



That's the effect of recombination on genes. Recombination, instead of keeping me on the same chromosome that Greg and I were on, will actually end up putting me into a different body. Okay? So in a sexual organism the gene that's controlling the mutation rate becomes disassociated from the genes whose mutations it might try to control, and therefore even though down in my ride to New York I invent some kind of great process that would benefit Greg, he is now dissociated from it and he doesn't get to benefit from my adaptations.



So it is much more plausible that we will see genes that are controlling mutation rates evolving in organisms like bacteria and viruses than it is that we will see mutations that control mutation rates evolving in us. There is some reason to think that there is weak selection on them, but it's not as strong as it is in bacteria. And in fact, interestingly, in bacteria you can do experimental evolution and show that the mutation rate will evolve up or down, depending on the circumstances that you put the bacteria under.



These are some representative mutation rates, and it's good to have some general framework to think about--how frequent is a mutation? So the per nucleotide mutation rate in RNA is about 10-5; in DNA it's 10-9. So if you start evolving in an RNA world, and you want to lower the mutation rate because your information is getting eroded and you can somehow manage to engineer DNA as your molecule rather than RNA, you can see that you would be able to pick up four orders of magnitude by doing so. That's just because DNA is more stable.



DNA is a remarkably stable molecule. It's possible to recover DNA from fossil bones. Svante Paabo is in the middle of a project to sequence Neanderthal's genome. He's already got significant chunks of Neanderthal sequence. So DNA is just a remarkably stable molecule. The per gene rate of mutation in DNA is about one in a million; so this is like per meiosis. The per trait mutation rate is about 10-3 to 10-5. The rate per prokaryotic genome is about 10-3, and per eukaryotic genome it's between .1 and 10.



I once saw a really great talk by a guy named Drake, Frank Drake, from NIH--this was like at a big international meeting--Drake walks up to the blackboard and he writes 10-3 on the blackboard; he's going to give a talk about mutation rates in prokaryotes. He talks for 45 minutes about this number; no PowerPoints, nothing else, he's just speaking very animatedly about how it was that just about all viruses and bacteria appear to have converged on roughly this per generation mutation rate, per genome, which is pretty strong evidence that it's an optimal rate; thousands of species have converged on this rate.



And I asked him how it was that he gave this great talk without any slides, and he said that he had lost them in the airplane, and that had happened about ten times before, and it was such a great talk without the slides that he just switched completely. So a couple of years ago, actually early last year in this course, I tried giving talks without the PowerPoints. Ninety percent of the class didn't like it and it ten percent of the class did. So that's why you're still getting PowerPoints. Okay?



Now what is your mutation rate? Well each of you has about four mutations in you that your--new things, your parents didn't have, and about 1.6 of those are deleterious. So this is something that's always going on. And there are about 100 of us in the room; that means there are somewhere around 150 new, deleterious mutations, unique in this generation, sitting here in the classroom.



Where did they happen? Well they happened fifty times more in males than in females. And there are good biological reasons why. There are many more cell divisions between the formation of a zygote and the production of a sperm than there are between the formation of a zygote and the production of an egg. In human development, and in mammal development, egg production pretty much stops in the third month of embryonic development, at which point all the women in this room had about seven million eggs in their ovaries.



Since then oocytic atresia, which means the killing of oocytes, has reduced the number of eggs in your ovaries down by nearly seven million. When you began menstruating you had about 1500 eggs in your ovaries. You've gone from seven million down to 1500. When you were born you had gone from seven million down to one million; you'd lost six million of them before you were even born. It appears to be a quality control mechanisms, ensuring that the oocytes that survive are genetically in really good shape.



So there are very, very different kinds of biology affecting the production of eggs and sperm; females have a mutation screen that males do not. Well the result of that is that there are more mutations in the sperm of older males; they've lived a longer time. Anybody that wants to get in to mate choice and what kinds of reproductive strategies should result from this simple fact is welcome to write a paper on it; there's literature out there. Okay? Not very PC, but it's very biological.



Okay, recombination. What does recombination do to this mutational variation that builds up in populations? Suppose we had ten genes, and each of those genes had two alleles, and each of those was on a different chromosome. That would mean that just looking at those ten genes, on those ten chromosomes, we could get 310 different zygotes. Can anybody tell me why?



Student: [Inaudible]



Professor Stephen Stearns: How many genotypes are there for the first gene? How many different combinations of Aa are there? Three: AA, Aa, aa. So there's three things that the first gene can do. There are three things that the second gene can do. There are three things that the third gene can do. And there are ten genes. So we multiply them to get the number of different combinations, and if they are independently sorting on different chromosomes, that will result in 59,000 different zygotes.



Now if we had a real eukaryotic genome that had free recombination--which we don't have--and unlimited crossing over--which we don't have--then the number of possible zygotes is about 315,000 or 350,000, somewhere along that, that order of magnitude. Well the number of fundamental particles in the universe is only 10131. We're talking about numbers which are just inconceivably large. That means that in the entire course of evolution the number of genetic possibilities that are present, just sitting in you, have never been realized. There is a huge portion of genetic space that remains unexplored, simply because there hasn't been enough time on the planet for that many organisms to have lived.



Now, how--you can see that this would be free recombination with independent assortment of chromosomes. That makes it easier than if it's crossing over, because crossing over happens more frequently the farther genes are apart on a chromosome, and it doesn't happen very often when they're close together. So there's been an evolution of the chromosome number of a lot of species.



And I've previously told you about ascaris. Ascaris is a nematode that lives in the gut of vertebrates. There is an ascaris that lives in dogs, there's an ascaris that lives in us, and it just has one chromosome. So that's kind of one limit, things with one chromosome. There are species that have hundreds of chromosomes. Sugarcane has I think about 110 chromosomes, something like that.



So the chromosome number of the species itself evolves, and it can evolve fairly dynamically. There are actually some populations within a single species that have a different chromosome number than other populations within that species, and when individuals from those two populations meet and mate with each other, the offspring often run into developmental difficulties because of this difference in chromosome number. There is such a, uh, contrast in house mice in Denmark. There's a spot where there's sort of a hybrid zone in Denmark, and the house mice on one side of the hybrid zone have difficulty--uh, they're in the same species, but they just have different chromosome numbers--and they have difficulty dealing with the house mice on the other side of that hybrid zone.



The difference in chromosome numbers appears to have arisen in the house mice during the last glaciation, and they recolonized northern Europe from different places. Some of them came up from Spain. Some of them came up from Greece. They got together in Denmark and they ran into problems.



Okay, now crossing over also generates a lot of genetic diversity. And the amount of crossing over can be adjusted. Inversions will block crossing over. You take a chunk of chromosome and flip it around, so that in the middle of the chromosome the gene sequences are reversed, and in that section of the chromosome the inversion causes mechanical difficulties. It actually changes the shape of the chromosomes when they line up next to each other, and it inhibits crossing over during meiosis.



This is one way of taking a bunch of genes that happen to have really helpful interactions with each other, and locking them up in a combination, so that they don't recombine. That has happened, and it's thought to be important in the evolution of quite a few insects, for example.



Now we can play the mental game of asking ourselves what would happen in a sexual population if we just shut off mutation? We can't actually do it, of course. But how long would it take before we would even notice that evolution had been shut off, if we were just observing the rate at which that population was evolving?



And the answer to that is kind of interesting. We could wave a magic wand over a moderately large sexual population, completely shut off mutation, and the impact of recombination on the standing genetic diversity in that population would create so many new diverse combinations of genes that it would take about 1000 generations before we would even notice that mutation has been shut off.



So think back to the beginning of the lecture. I said mutation is the origin of all genetic diversity; and that's true. But once mutation and evolution have been going on for awhile, so much genetic diversity builds up in populations that you can actually shut off mutation and mutation--and evolution will keep going for quite a while. After 1000 generations it'll run out of steam and stop; but it takes quite awhile.



Okay, so where genetic came--where genetic variation came from and how much there was, was a huge issue and caused a lot of research and controversy for about fifty years. Before 1965, there was the concept of a wild type out there. After 1965--so there was one really good genome, and then there were a few mutations.



After 1965, with electrophoresis, the impact of Clement Markert's work, and Dick Lewontin, and his colleague Hubby, we've recognized that there's a lot of molecular variation. This concept that each species has a certain genomic type is no longer tenable. There's just a tremendous number of different kinds of genomes out there. Since 1995, we've had a lot of DNA sequence variation and now we've got genomics.



So I want to illustrate the impact of genomics with something that's just become possible in about the last four years. The HapMap Project was done after the human genome was sequenced, and the motivation of it was to try to associate diseases with common genetic variants. By the way, the upshot of that effort is genes don't normally account for very much, usually about two or three percent of the variation; but that's another story.



So basically once we had the human genome, it was clear that we could then look for places in genomes that had single nucleotides, that were different, between one person and another; these are called single nucleotide polymorphisms. And to do this the HapMap Project looked at regions of the human genome that were about 10,500 kilobytes long, for 269 individuals. So that's 10,500,000 bases, for each of 269 individuals. And they did it on people from Nigeria, Utah, Beijing and Tokyo. And they discovered that our genome is arranged in blocks.



There are, within each block, within each let's say rarely recombining section of DNA, there are about 30 to 70 single nucleotide polymorphisms, and that means that you could design a genechip just to pick up enough of these to tag a person as having that particular block of DNA. Okay? So now there are these genechips, and we've discovered that there are some SNPs that are associated with disease. We can see that there are portions of the genome that show signatures of recent selection. This is an interesting literature.



This is what a little section of our chromosome 19 looks like. Okay? So this is the position along the chromosome, starting at 40,000,000, and going up to 50,000,000 base pairs. The little black dots are all the genes that are in this section of the chromosome, and using the single nucleotide polymorphisms, you can identify people as having a segment of DNA that is not recombining very frequently. And you will notice that they are actually lined up right over places where the recombination rate is pretty high. So you can see breaks in this upper diagram here, showing places where the recombination rate is pretty high.



So remember, this was done over the entire genome, all of our 23 chromosomes. I am only showing you one tiny part of one chromosome here, and there are actually 650,000 of those blocks that have been identified now in our genome.



So three years later a group then goes out and takes 928 people, from 51 populations, and looks at how much haplotype diversity there is. Remember, a haplotype is a block that's got some specific nucleotide polymorphisms on it. The Y axis here has 650,000 entries on it. Of course they all blend together, it's hard to see them. The X axis has 928 people arranged across it. This is a sample of human genetic diversity on the planet. You can see there's quite a bit. You can see different colors. Okay?



Now if you take this and you then use the tools of phylogenetic analysis to ask what kind of historical structure is there in this data set, this is what you get. You get a group in Africa. You can see the emergence of mankind from Africa--this is thought to have happened about 100,000 years ago--and then you get a very, very nice genetic trace of our expansion across the globe.



We paused for awhile in the Middle East, before we broke out. We were in the Middle East up until about 50,000 years ago, and then there was a group that went into Europe, and other groups then split off from that and set off into Asia. And about probably 40,000 years ago people went to Papua New Guinea and Australia, and probably somewhere around between say 15 and 20,000 years ago, a group of people headed off over the Bering Straight for North America, to become Native Americans, and then another group diversified in East Asia. So there is a huge amount of information in the history of genetic variation.



So what I'd now like to do is give you four general reasons why this much genetic variation could be maintained in any population. If you look in the textbook you will see that there is also a tremendous amount of genetic variation in wild populations of practically any species, just as there is in humans. In humans it happens to be better analyzed than in almost any other species. But something like that can be done for any species on earth now, and it's getting cheaper and cheaper and cheaper to do so.



So selection and drift can both explain the maintenance of genetic variation. And for a long time there was a fight within evolutionary genetics about whether what we saw was being explained by selection or drift. It appears not to be a productive question. It's extremely difficult to answer, in any specific case, whether the pattern you see is because of a history of natural selection or because of a history of drift. Both of them are capable of generating quite a few patterns, and those patterns overlap.



So if you take a very specific case and study it in detail, you can give a leading role to selection or to drift. For example, you can find a signature of selection in a portion of a human chromosome, indicating that there's a gene there that perhaps was affected by a specific disease; that's been done. But the general answer, for all species across the planet, about whether selection or drift is more important, probably is unrealistic. It's probably not a fruitful research effort to try to answer this question.



So here are the situations that can maintain genetic variation in principle; there are four of them. There can be a balance between mutation and drift; a balance between mutation and selection; there can be heterosis or over-dominance; and there can be negative frequency dependence. So I'm going to step through these now and give you some feeling for how the thinking works on each of them. In so doing, we're going to be dealing with equilibria, and really there are other ways of approaching the analysis, but the equilibrium approach is the one that allows you do it with simple algebra, rather than with complicated computer models. We do it for mathematical convenience.



We do it also because the periods during which things are in balance may be pretty long, compared to those in which they're dynamically changing--that does appear to be a message of evolution--but with respect to this particular question of the maintenance of genetic variation, we don't really know too much about those periods. Selection can go back and forth; populations can appear to be in stasis when things are going on inside of them. This question is really unresolved.



We do know that in terms of our immune genes that we share certain polymorphisms with chimpanzees. Those appear to have been things that evolved in terms of disease resistance before humans and chimps speciated, about five to six million years ago. So certainly that genetic variation is five to six million years old. We don't have too many cases where we know that, but there may be many more out there, just undiscovered.



A little terminology. The fixation probability of a mutation is the probability that it will spread and be fixed in the population. That's equal to its frequency, at any point in time. The fixation time is how long it takes to become fixed in generations. And I put these ideas up on the board earlier, and I'd like to go back to that, because I'd like to have reference to it in a minute.



So if this is frequency here, it can go from 0 to 1, on the Y axis, and if this is time, over here, this can be many thousands of generations. And the fate of most neutral alleles, when they come into the population, will be to increase in frequency for a little while and then drift out. They have low probability of being fixed because when they first originate they're very rare, and the probability of eventual fixation is just directly equal to their frequency. So in a big population most mutations disappear. But every once in awhile one will drift through, and when it reaches frequency 1.0, it's fixed. Okay?



So the fixation probability is the probability that out of all of the mutations that might arise, most of which drift out, this one will be fixed; and that's a small number. And the fixation time, how long it takes to be fixed, is on average how long it takes for this process to occur. So that's the fixation time, and that's an average of many such events. So this picture that you're looking at on the blackboard is really just supposed to be an evocative picture, not some kind of precise, concrete state. Because it's representing many, many different genes, they are occurring at all the different possible places in the genome.



Now for a neutral allele, like the one that I've been sketching there, the fixation rate is just equal to the mutation rate. That doesn't depend on population size. The probability of fixation, as I said, is equal to the current frequency. For a new mutation, one of these guys down here, right at the beginning, that's 1/2N, to be fixed, and 1-1/2N to be lost. That means that most of them are lost. N is the population size. N is a big number.



Because there are 2N copies of the gene in the population, and if mu is mutation rate, that means in each generation there are 2mu new mutations, and for each of them the probability of fixation is 1/2N. So the rate of fixation of new mutations is about 2mu times 1/2N, which is equal to the mutation rate. That's about 10-5 to 10-6 per gene, and that means the molecular clock is ticking once every 100,000 to once every 1,000,000 generations per neutral gene.



The fixation rate doesn't depend on the population size, and that's because the probability that a mutation will occur in a population depends upon how many organisms are there. You can think of all of their genomes out there as being a net spread out to catch mutations--the bigger then net, the more the mutations are in any given generation--and that will just exactly compensate for the fact that it takes them longer to get fixed. The bigger the population, the longer this process takes. But the bigger the population, the more of these are actually moving through to fixation. Those two things exactly compensate. Okay?



In a small population most of them are lost. The few that do reach fixation, reach it rapidly, and in large populations more new mutations are fixed, but each one does it more slowly. Those things compensate, and the fixation rate doesn't depend on population size, if you're looking at the whole genome. The number of differences fixed over the whole genome doesn't depend on the size of the population.



Now there is a technical concept in evolutionary genetics called effective population size, and that is the size of a random mating population, that is not changing in time, whose genetic dynamic would match those of the real one under consideration. And so we know that there are lots of violations of these assumptions. Okay? Populations don't have random mating. They are changing in time; ta-da ta-da. How do we take a real population and then transform it into something that's really easy to calculate?



Well, there are methods of doing so. The factors that will have to come into consideration are variation in family size, inbreeding, variation in population size, and variation in the number of each sex that is breeding. And so just to illustrate one of these, to give you some idea of its impact, look at cattle in North America.



There are about 100,000,000 female cattle in North America. They are fertilized by four males, on average, through artificial insemination. So there are four bulls that are inseminating 100,000,000 cows. Genetically speaking, how big is the population? It's just about 16. Okay? So by restricting one sex to a very small number, we have restricted one pathway that the genes can go through to get to the next generation. And by making the male side of it so small, we have biased the probability that a gene will get fixed according to some process like this.



That male side is a really small population. So it completely outweighs the fact that there are 100,000,000 females there. Because if you think about it, every time one of those genes goes through a female and goes into a baby and grows up the next generation, it's going to go back through the male side of the population--right?--as you go through the generations. And these formulas that have been developed give us the opportunity to take that complex situation and make a quick, useful, back of the envelope calculation of how we can expect genetic drift to be going on in cattle in North America. Basically they are a small population.



So that's the basis of a mutation-drift balance. The amount of genetic variation in a population, in a mutation-drift balance, is just a snapshot of the genes that are moving through it. If I were to go back to this diagram, and I were to put more genes into this process, and I were to ask you to go out and take a sample out of a population at any given time, you would take the sample at some time and you would tell me that's how many genes we have, that's how many are moving through. Okay?



Now the second possibility for a mechanism that will maintain genetic variation is a balance between mutation and selection. Mutation brings things into the population. Selection takes them out. So if we had a haploid population, with N individuals, and we have a mutation rate mu, we're getting Nmu new mutations each generation. The key idea is that if there is a mutation selection balance, then the number going in equals the number going out; that's what would keep this mechanism balancing the amount of genetic variation in the population.



And so if the mutant individuals have a lower fitness than the non-mutants, and if q is the frequency of the mutants, then selection is taking out NSq mutants per generation. And at equilibrium, with the number coming in equal to the number going out, the number coming in equals the number going out, and that gives us an equilibrium frequency of the mutation rate divided by the selection coefficient. It's a very simple result.



And if you do the same kind of thinking for a diploid population, you get that the equilibrium frequency will be the square root of the mutation rate, divided by selection for recessives, and the same as it is for haploids for dominance. Okay? So there are some examples of this.



There are rare human genetic diseases, such as phenylketonuria--that's the inability to metabolize phenylalanine. It has a frequency of about 1 in 200,000, in Caucasians and Chinese. It is probably in selection mutation balance. It's at low frequency but it's present in a population. People with it suffer a selective disadvantage. It keeps mutating and coming back in, and it keeps getting selected out. The result is balance, okay, and it's pretty rare.



The third mechanism that will maintain selection in natural populations is a balance of selective forces; that is, where the heterozygote is better than either homozygote. And there is a classic, famous case, and it's always discussed in this context, and it's interesting that it's the one that's always discussed in this context, and the answer is it's been hard to find more. [Laughs] Okay? That's sickle cell anemia.



Now this is the normal heterozygote which is susceptible to malaria. The heterozygote is resistant to malaria, and the sickle cell homozygote is anemic and sick. And it sets up this kind of relative fitness. And, in fact, if--H here is actually going to be a negative number. Okay? So the fitness of the heterozygote is going to be higher than the fitness of either homozygote. And you can then set--the equilibrium frequency is going to be the one where P prime is equal to p; in other words, the frequency in the next generation is just the same as the frequency in this generation.



At what frequency does that happen? Well it happens when these little equations are satisfied. And the interesting thing, when you look at them, is that the selection coefficient has dropped out of them. The equilibrium frequency doesn't depend on the selection pressure, it depends on how frequently the gene is expressed in a heterozygote. So it depends really on the heterozygote advantage.



Now the real situation is more complicated than this. There are several such sickle alleles. They're changing frequency. The equilibrium assumption doesn't really apply out there in Nature, but it does give us a rough rule of thumb for how much to expect, and as soon as people who have sickle cell anemia move out of areas with malaria, it takes quite awhile for that allele to disappear from the population.



The fourth mechanism is a balance of selection forces, so that, for example, for A2, when A2 is 0, it has high fitness here, and as it increases in frequency its fitness drops, according to this equation. Now the frequencies of A1 are just reversed along this axis. A1 is 1.0 here, and it's 0 here. A1 has low frequency--has low fitness when it's at high frequency, and high fitness at low frequency. A2 has high fitness at low frequency; low fitness at high frequency. So both of them do better when they are rare. And I think that you can see intuitively from this diagram that at equilibrium they will stop changing when their fitnesses are exactly the same.



Now there are some interesting examples of this sort of thing. One is Ronald Fisher's classical argument on why 50:50 sex ratios are so common; why in many populations we see half females and half males. The deviations from that are interesting. This kind of thing happens with evolutionary stable strategies, and those are the solution to many problems within evolutionary game theory. They are also called Nash equilibria, under certain circumstances, and they are important in economics and political science as well.



And the tremendous amount of genetic variation in the immune system is thought to exist for reasons of frequency dependent selection; basically pathogen resistant genes gain advantage when they are rare, because when they're common, the pathogens evolve onto them. They are more or less sitting ducks; they're a stable evolutionary target.



But as they become more common and more and more pathogens evolve onto them, and those organisms get sicker and sicker, the ones that are rare have an advantage. And then as they start to increase in frequency, the same process occurs; the same process, it continues again, and after awhile you've got hundreds of genes, each of which is advantageous at low frequency, and none of which are advantageous at high frequency.



So this is a very important kind of mechanism maintaining genetic variation in natural populations, including our own. If we look at quantitative traits, such as birth weight--here's a classical example. This is for babies born in the United States in the 1950s and 1960s, and this is the percent mortality for babies of different weights. You can see that there's stabilizing selection that's operating to stabilize birth weight right at about 7 pounds, and there's variation around it. And you might wonder, why is there any variation around that? Why don't all babies have the optimal birth weight? It's such an important thing. And there are really two answers to that.



One is that there are evolutionary conflicts of interest between mother and infant, and father and mother, over how much should be invested in the infant, and these lead to some variation. And there's mutation selection balance. So that this is a trait which is probably determined by hundreds of genes, and at each of those genes mutations are coming into the population, and at each of those genes there is a mutation selection balance, and when you add that up, over hundreds of genes, you get quite a range of variation. Of course, some of this variation is also due to developmental effects of the environment; variations in the mother's diet and other parts of her physiological condition during pregnancy.



So to summarize. The origin and maintenance of genetic variation are key issues; mutations are the origin. Recombination has huge impact. There's a tremendous amount of genetic variation in natural populations. Remember that data from the HapMap Project on us, on humans, and that all of the differences that you have, in single nucleotide polymorphisms, from the person sitting next to you, and how you share them with people who have had a similar history since we came out of Africa.



We can explain the maintenance of this variation by various kinds of mechanisms, principally for balance between mutation and drift, between mutation and selection, and by some kind of balancing selection, either heterosis or frequency dependent selection. And we think that variation in many quantitative traits--human birth weight, human body size, athletic performance, lots of other things--is probably maintained by mutation selection balance, as well as by other factors. So next time I'm going to talk about the role of development in evolution.



[end of transcript]

Development is responsible for the complexity of multicellular organisms. It helps to map the genotype into the phenotype expressed by the organism. Development is responsible for ancient patterns among related organisms, and many structures important to development shared by many life forms have changed little over hundreds of millions of years. Development is expressed combinatorially, allowing a relatively small amount of genetic information to be expressed in many different ways.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 6

Transcript



January 28, 2009



Professor Stephen Stearns: Today we're going to talk about, or we're going to introduce the role of development in evolution, and I would like to start by asking you to make two jumps in your head. In the first case I want you to think of yourself as inside a single-celled bacterium. If you go to a good book on the gene networks and the biochemical networks that can be found inside a single-celled bacterium, you will be stunned by the complexity of it and you will deeply hope that you never have to reproduce it on any examination, because there is so much of it. Okay?



That's inside one cell. Development doesn't arise until we get to multi-cellular organisms. And if you were able to go into the body of a multi-cellular organism, such as yourself, and look at all the signaling pathways, all the way that information is transferred and integrated in a multi-cellular organism, it's just as complex as the whole picture down inside that one single-celled bacterium.



So there are two huge kinds of orders of magnitude, levels of hierarchical complexity of information integration that happen in a multi-cellular organism like yourself. We call the way that the information in the genes maps into the structure of the genotype the genotype-phenotype map. It takes us through all of that complexity to produce something that we can then try to understand, which is a whole organism. Another name for the genotype-phenotype map is development. Okay? And what I'm going to try to show you today is that out of this almost unimaginable complexity, two hierarchical layers of orders of magnitude of information, biologists have been able to extract some interesting simple rules and show that there are some large-scale patterns in evolution.



However, that task is far from done, and the understanding of the genotype-phenotype map, or the understanding in general of developmental biology, remains probably the most pressing issue in basic research in biology for the twenty-first century. It's something that occupies some of the best faculty in this department and some of the best scientists across the globe. So it's a basic issue. And the thing that I hope you take home from this lecture today is that it's important, both for microevolution, and for macroevolution.



Today I will be talking about patterns that are pretty large scale, they are more macroevolutionary; and next time I will be talking about patterns that arise within populations that reflect that macroevolutionary history, but that have immediate consequences for microevolution. So development isn't simple. It's going on both at large scale, over long periods of time, producing patterns, and it's going on at a very, very short scale in every generation, as each individual grows up and turns into an adult.



So what's involved in development? It isn't really just the production of the adult form from an egg. It is the living of the entire lifecycle, from the formation of the gamete, through the adult, through all the changes the adult goes through until it dies and produces the next generation. So development refers to the entire lifecycle, and evolution shapes the entire lifecycle.



So something that we get from a very important discovery in nineteenth century biology is that all of life is made of cells. It could've been organized differently, and in fact there are interesting science fiction novels, like Solaris, by the great Polish science fiction novelist Stanislaw Lem, that conceptualizes what life would be like if it were not cellular. For example, what if the whole ocean were one living thing? But we know that that's not the way life is on our planet.



On our planet life is all built out of cells, and that means that the problem of development is a problem of communicating between cells. And cells are all set up as information signalers and receivers. They have cell adhesion molecules on their surfaces. They produce information molecules, hormones, and other signaling molecules for export. This information is used to change the fate of a cell.



Now every cell in your body has all the information in it that's needed to build you, and that is true of virtually every organism. The only exception in us is our red blood cells because they don't have any nuclei, so they don't have any DNA in them. Okay? But in every other organism that we know of, with minor exceptions like our red blood cells, all the information is in all the cells, and that means that development is a matter of editing, it's a matter of determining which information gets turned on in the right place at the right time. So the evolution of development is about shaping those patterns in space and time, within the framework of an organism, to produce something that works.



Development does a bunch of things in evolution. One of the important ones is that it has a strong role in the course of the production of individual organisms in shaping the kind of variation that is presented to selection. Okay? So the developmental mechanisms that are shared by particular organisms determine that only certain kinds of phenotypes are going to be produced--and there's a lot of variation within those phenotypes--but they are a tiny portion of phenotype space.



And this is why we actually see, morphologically, the Tree of Life. This is why dogs look like wolves. This is why humans look like chimpanzees. This is why birds look like birds and we can call them birds. It's because they share developmental pathways that have been inherited from ancestors and that have constrained the range of phenotypes that can be presented to selection.



Now there's another important thing about development. You might think that you could conceive of the body as produced by an engineer, but it's not really constructed that way in evolution. What goes on is that genes can only build organisms out of the materials that are available at a certain time, and then there is an evolutionary memory, of which materials are selected, and of the control systems that are used to shape the phenotype with them. Now I'll give you a couple of examples.



What is the cell membrane? The cell membrane is a lipid bilayer, and it's been--it's actually a marvelous organ now; it has all sorts of special channels in it, things that are filters to let particular stuff in and keep other stuff out. It's been heavily modified by evolution. But there is no way that you can take simply the DNA sequence in the genome and get a reaction system that's going to construct cell membranes. All known cell membranes are actually constructed biologically by using pre-existing cell membranes as templates. In other words, the cell membrane itself is an information transfer molecule. So that's one.



There's another, and that's bones. Your bones are made out of a material called hydroxyapatite, which is a calcium phosphate material. And hydroxyapatite has the following extremely convenient feature. If you take hydroxyapatite and you put it under stress, it will strengthen itself in the direction of the stress. That means that the genes don't have to have sensor systems to detect stress, and they don't have to worry about how they're going to make a bone strong in the direction of stress. All they have to do is say, "Hey, I'm going to use hydroxyapatite to make bones, and then when that baby first starts to toddle around and walk on its legs, its hips start getting strengthened in the direction of stress."



Now, in fact, there are modifier genes that then take this and use it to their own advantage, by building in protein molecules that strengthen the bone in the direction of the stress. Okay? But the initial signal, which direction is the stress coming from, is a freebie. It's given by the biochemical properties of a hydroxyapatite. So that's one, a second one.



Here's a third one, gastrulation. When vertebrate embryos, and many other embryos, grow, they grow up as a ball of cells which then becomes a hollow sphere of cells, and that hollow sphere of cells, which by the time it gastrulates has thousands of cells in it. You can think of it as a little pulsing basketball. Okay? It's a little sphere that's pulsing, and if you simply let this thing grow to a certain size, the tension in the actin tubules in the cells will cause it to spontaneously invaginate. So it'll get a dimple in it, like you pushed your thumbs into it.



This happens spontaneously. It is not as though the genes have to say, "I am going to construct a mechanism that's going to make my gastrula form. When my blastula turns into a gastrula, when my hollow ball of cells turns into a thing that's got a dimple in it, and then forms three cell layers, out of which I can make muscles and bones and skin and gut and all of that kind of stuff, when that happens that's a freebie." Okay? That is just in the tension of the actin filaments in an expanding ball of cells.



So these are some of the properties of the biological materials that organisms are constructed out of, and it means that on the one hand the genes don't have complete control over the phenotype, but on the other hand they are given certain things by the materials that don't have to be specified in the DNA sequence.



So where does development fit? I'm giving you real large-scale messages now. Okay? The biological disciplines that we call Ecology and Behavior actually deal with the processes that reduce the cohort of newborn organisms to the ones that survive to reproduce. Okay? Ecology and Behavior actually study the mechanics of natural selection, while they study a lot of other stuff as well. But that's the level at which that happens.



Genetics takes the genotypes of the parents and it transforms the genotypes of the parents through Hardy-Weinberg equations, through the selection that's operating on them, through all of that stuff that we just looked at quickly. It takes the genotypes of the parents and transforms them into the genotypes of the offspring. Okay? So genetics is all about information transfer. Lots of people that like computers do pretty well at genetics.



What development does is it takes that information in the genotype and it maps it into the material of the phenotype. You can think of development as being a big transduction mechanism that takes material--takes information and turns it into material. Okay? And, in the process, it places limits on what the phenotypes can look like, so that not every conceivable phenotype is going to arise out of the DNA sequence in a genome; only a certain range. Flies are going to look like flies, sheep are going to look like sheep, and daffodils are going to look like daffodils.



If we look at what development has been able to produce, well. in a large-scale it has produced some very basic things, and we can see that by a comparison of the body plans of the major groups of organisms. I'd just like to take a moment here and see if I can elicit from you some sense of what it is that we're looking at. Okay? I assume that you're all pretty comfortable with chordates, because that's what you are. Okay?



Can anybody tell me what a bryozoan is? A bryozoan is a moss animalcule; it is a moss animal. Bryozoans produce beautiful exoskeletons, and you can find them on tropical reefs. Anybody comfortable with what a priapulate is? A priapulid is a deep-sea worm that forages with a tentacle and when you pull it out of its hole, it looks like a penis; which is why it's called a priapulid. Okay? What about a tardigrade? Tardigrades are little water bears. Okay? They look a little bit like insects or crustaceans, and they're very tiny, and they're extremely cute. Okay? So tardigrades are water bears. Arthropods, who's in the arthropods? Insects are arthropods. What are the other big groups of arthropods?



Student: [Inaudible]



Professor Stephen Stearns: Crustaceans; yes spiders, spiders and their relatives. Arthropods are anything with jointed legs--that's just Greek for jointed leg, arthro-pod. Pogonophorans? A tiny phylum of worms that live in the sand and are living fossils and haven't really changed their morphology for about 400 million years. So there's a lot of big-scale stuff here.



This is basically the animal kingdom. Okay? And it's formed into these groups. And just to give you a little bit of timeline, it's about 600 million years, 700--Bilateria, yeah, six or seven-hundred million years ago. A lot of stuff happens really quickly, because from this point to this point here is only about a hundred million years. At this point we're still 500 million years ago. Okay? So this is big-scale stuff. The cnidarians and the ctenophores formed trace fossils in the pre-Cambrian ooze. So they may go back a billion years; not sure about how far back.



So if you look at what happened when multi-cellular organisms formed and one branch of them went off to become animals, this is what development was able to produce. It could produce body axes--front and back, left/right; produce a skeleton, organ system, symmetry and cell layers. And figuring out the shared general mechanisms by which development can produce those things, and then how evolution can tweak them to make them different in these different groups, is evolutionary developmental biology, or evo-devo.



There are some big and striking differences among these groups. For example, this group up here has an exoskeleton, and this group down here has an endoskeleton; and that places very fundamental constraints on growth, size, all kinds of things.



What can it do in plants? Well here is an extremely sketchy view of the plant world. And, by the way, I would've used a much more complex view of the plant world than this one, but this is the one which is publicly okay without copyright protection. Okay? So for you plant biologists that are worried about the view of the plant world, this is pretty simple.



Basically what this does is it takes you from ferns and their relatives through cycads, ginkgoes, pine trees and fir trees; the gnetophyta, which have some really cool plants that live in Namibia; Wellitschia and other things like that are gnetophytes. And then the magnoliophyta are all flowering plants, going out here. So this is a huge group down here. And if you look at that, what has development and the evolution of development been able to produce? Well these guys are all variations on the following themes: a meristem-root axis; where xylem and phloem appear; where wood appears; the kinds of branching patterns they have; whether they have naked or covered seeds; whether they have leaves; and whether they have flowers.



So you can see that the image that I'm trying to create here, in both plants and in animals, is that there's certain shared general features, and that what evolution has done is that it has made many, many different combinations of those features, to create the diversity that we see, and that this is done through the evolution of development.



Mechanistically a lot of this is going on at the level of gene regulation; and this is a recap of the structure of the eukaryotic gene. And the parts that I want you to focus on right now are the promoters and the enhancers. So these are parts of the DNA molecule that receive a signal, which says turn this gene on or turn it off. And I want to show you just exactly what kind of a network of information that results in.



You can think of there being regulators--and we will talk a little bit about what kinds of regulators are used early in development--and that these then feed into a signaling cascade where a signal goes out, there's a receiver, there's a transducer that turns that signal into a transcription factor. A transcription factor then is going to go out and it's going to bind to the enhancer region of a gene, or a promoter region of a gene.



Okay, so it's bringing in a signal. The signal might be either turn it on or turn it off, but it's bringing in a signal; that's what a transcription factor will do. You can think of there being other pathways and other signals going through them, and they can turn on transcription factors, and some of those will come down and sit down on the same gene. It isn't all only one transcription factor that can sit down on one gene.



In an average gene in Drosophila there are about ten to twenty binding sites in its control region. That means that ten to twenty different transcription factors can sit down on a single gene, and one transcription factor can bind to the control regions of anywhere from one gene to several hundred genes. Okay? There are about 13,000 genes in a drosophila genome.



So that gives you some idea of the array of possibilities of turning all those things on or off, as you go through. That is a huge array of possibilities, and I think you'll see, when I show you later, how you take an onychophoran worm and turn it into a Drosophila, that you could imagine evolution might have had to use a lot of them, in order to turn something like a worm into something like a fruit fly.



There is another way to think about this. Think about the control region of a gene as the keys on a piano, and think about the transcription factors as the fingers on the hand of the person who's playing the piano, and think about evolution as the composer who wrote the score. You know perfectly well that you can play all kinds of tunes on the keys of a piano, and you know perfectly well that there are traditions in music of different kinds of related music. So anyone who has listened to Bach is probably going to recognize Telemann, and people who have listened to Schoenberg are going to recognize more modernist composers.



So you can think of those as being clades, and you can think of the cultural tradition as being inherited, and there's constraining variation within the range of scores that are composed on the piano. Of course, what we're dealing with in a genome is like the biggest symphony orchestra you ever saw in your life. Okay? So it's much, much bigger than that.



So a few points about the control of development. At the beginning of development, when the first cell is getting set up to divide, and in the formation of the very early multi-cellular stages, there are concentration gradients that are produced. So before the first cell divides, there will be like a front end and a back end of the cell, and chemistry will get set up to produce molecules that then form a concentration gradient across the cell, and the concentration of those molecules is positional information on what's the front and what's the back. And as the cell divides, it retains that information on where it is in the front or the back.



That's how the Drosophila embryo is set up. And we will also see that this kind of concentration gradient is used in the construction of the vertebrate limb. By the way, the signaling center on the vertebrate limb, when it's just a little paddle of cells, is basically in the armpit. Okay? So if you want to think of smelly molecules being produced, think armpits.



What then happens is that transcription factors are used to define specific areas where only a precise subset of genes is expressed. So remember, all the info in the whole genome is in every cell. You only want a certain subset for this part of the organism that you're making. So the gradient, the chemical gradient then sets up gene expression, and the transcription factors appropriate to that position get turned on.



Genes are regulated by combinations of activators and repressors, and this combinatorial control is what gives you the huge diversity of cell specific gene expressions. When I say combinatorial control, think of composers writing notes and people playing pianos; that's combinatorial control too. All the music that's ever been written, that can be played on a piano, is simply a variation on all the combinations of those keys in space and time.



So, the control can get complex. It can be a cascade of information, and genes that produce transcription factors can be regulated by genes that produce transcription factors. And this sets up situations where genes can switch their roles. It is not correct to think that there are some genes that are early development genes, and then there are other genes that are adult genes.



Genes are used flexibly, in many different contexts, depending upon the information that's coming in to regulate them. Certainly there are some genes that are quite important in the embryo, but it turns out they also play a role in the adult. We'll see a case of this a little bit later.



Not surprisingly it's the genes that determine the general pattern that switch on first, and the ones that are controlling detail switch on later. So when I say 'general pattern' I mean--for example, in the vertebrate embryo, the front and the back, the top and the bottom, the left and the right: that gets laid down first.



Then the embryo gets chopped up into a sequence of segments. Some of them turn into the head, some of them turn into leg segments; some of them have extremities, some of them don't--that kind of thing. Okay? So this sequence of how the early general pattern gets set up, and then how the details are developed, that's all developmental genetics, and that's produced in evolution a whole lot of stuff.



Now, a little bit of vocabulary. You're going to hear, in this area, about boxes. Okay? You're going to hear about homeoboxes, MADS boxes, stuff like that. I want to tell you what boxes are. They are very highly conserved sequence motifs, and they are found in the DNA that codes for a particular family of transcription factors.



The reason that this sequence--by the way, it's about I think--I think it's about--I'm not sure whether its seventy to eighty codons, or seventy to eighty nucleotides long. But these boxes are not too long. They're conserved because they have a very important function, and that is to bind to the DNA. So they have a helix twist, helix structure, and that means that if the DNA molecule is here, this part of that protein, this part of that transcription factor, is going to fit right into it.



And it's because they are transcription factors--the boxes are found in transcription factors--that this is a very conserved interaction. Because DNA hasn't changed its structure in three billion years. So if they're going to bind to it, they have to have that structure, and so selection has made sure that that sequence is preserved.



They're called boxes simply because if you lay these DNA sequences out, if you sequence a lot of DNA, and you are looking for one of these things, what you find is that wherever there's a transcription factor, there is a stereotypic sequence. And the people who were analyzing this, first on computer printouts, or now with imaging on computer screens, drew boxes around them, to locate them. That's why the word 'box.' Okay? So when you see one of these in a DNA sequence, you know you probably have a gene for a transcription factor.



Here's the homeobox family. Okay? There are thirteen homeobox genes that have been identified. And this is from a number of years ago; this has probably been filled out now. And they have two--well there's more than two striking things about them. But the first thing that's striking about them is that they're deeply conserved. That means that they have retained so much of their sequence identity that you can recognize homeobox gene 1 in a human, and you can see that the same gene is there in flatworms and in earthworms, in priapulids and so forth. All the way through the animal kingdom this gene has been conserved, and you can pick up something like it in cnidarian.



And you wonder, well how did there get to be thirteen in this family? Well here you can see a gene duplication event right here. Homeobox gene 1 in the jellyfish and corals was duplicated right here--this was the expansion of the central HOX genes--and it happened here as well, so that now there were two copies. And that meant that this developmental control switch, which was an extremely clever piece of machinery to have around, now existed in two copies. You could use the first one to do whatever it used to be doing, and you can now evolve a new function for the second one.



This went on up until the time that the vertebrates started to evolve. And in our closest relatives there's one copy of the HOX gene, and it was duplicated twice. It was duplicated at the level of the Agnatha; so the ancestors of the sharks. And that means that all of the vertebrates, the higher vertebrates, have four sets of developmental control genes. Interestingly, the first set is still used to lay down the major body axis, and the fourth set is used to make a limb; that's the new function. Okay?



Now they have deeply conserved sequences, but they are also collinear. By collinear, I mean this. Look at the sequence on the genome, and look at what part of the body is controlled. The parts that are on one end control the head area, the parts on the other end control the tail area, and the parts in the middle control the stuff in the middle of the body.



There isn't any logical reason why it had to be this way. It's probably simply that when vertebrates first started--well when animals, prior to vertebrates, first started to get formed as multi-cellular things, this happened to be one convenient way to control development. But logically speaking, giving the signaling apparatus that's available in the genes, there's no reason logically that the genes have to be collinear; but it's a fact that they are, and it's a marvelous fact that they are. Okay?



This is just to show you that you can take homeobox genes and look at their DNA sequences and say, "Oh, they have similar DNA sequences." And then look at what parts of the bodies they control and see that a homeobox gene in a fly, that is homologous to a homeobox gene in a mouse, is controlling a similar part of the body.



So the things that are controlling the tail end, the green genes here, are expressed in this part of the fly and in this part of the mouse, and the things that are controlling the head end, that are expressed here in the fly, are actually expressed here in the mouse. That's kind of interesting, because it suggests that the mouse has added on some stuff that is in front of the hind brain.



So here's the vertebrate limb. Okay? And this is controlled by the fourth copy of the HOX genes, the D copy. And it shows you that if you have, for example, D9 being the only one that's turned on, you get that. If you have D9 and D10, you get that. You have D9, D10, D11, you get that. You have D9 through D12, you get that. And you get all five of these on and you get that. Okay?



So basically what this means is the following. If you just have D9 on, make a shoulder; D9 and D10, make a humerus; D9 through 11, make a radius and ulna; D9 through D12, make a wrist; and all five, make fingers. How simple, how logical. Remember when I said at the beginning we have these orders of magnitude of complexity within cells, and these orders of magnitude of complexity between cells. Out of all of that complexity, this simple pattern emerges.



Oh, and I forgot, notice that the genes are collinear in the limb. Okay? The ones that are on one end of the gene are controlling the shoulder, and the ones that are on the other end of the gene are controlling the fingers. So it's still collinear. It's the like the body axis, it's just been translated into a limb.



Well what about flowers? The MADS genes also have a sequence in them which shows that they're a transcription factor; there's a MADS box. M-A-D-S is an acronym for the original names that these genes had. Okay? Some of them started with an m, some with an a, some with a d, some with an s. Then after all that had happened, it was noticed that they were related. So people started calling them MADS genes.



They're scattered throughout the genome. They are not collinear. Okay? In Arabidopsis, they're on all five chromosomes. There's nothing resembling the HOX genes in the way they're genetically organized. They fall into three groups: the A group, the B group and the C group. So the A is not a single gene, it's a group of related MADS genes. B is another group of related MADS genes.



And within each of these groups the genes are sharing phylogenetic relationship. That means that the members of the A group are probably all duplicates of an ancestral gene; the members of the B group are probably duplicates of an ancestral gene for the B group; and so forth.



Now the neat thing about the MADS genes is the way they control flowers. And we're going to see that evolutionary developmental biology has a lot to do with the production of beauty. [Chuckles] Two of the best understood examples in evolutionary developmental biology are flowers and butterfly wings. Okay? So this is an area where researchers who go out to give talks get to use a lot of neat slides.



The ABC model of flower development goes like this. If only a gene from Group A is turned on, make a sepal; if only A and B are turned on, make a petal; if only B and C are turned on, make an anther; if only C is turned on make a pistol and an ovary. So the regulation of B and C is controlling male and female organ development. This is combinatorial. Okay? It's the same general logical principle.



However, it's with a completely different set of genes, and plants evolved multi-cellularity independently of animals, which means that plants invented development in evolution independently of animals. They both hit upon combinatorial control as a simple, logical way to control development. That probably means it's a very good idea. Okay? It's a very simple and economical way of expressing information.



Of course every gene has a history, and these MADS genes were doing something before they made flowers. In fact, if you go back and you look at the homologous genes in the plants that do not have flowers, you discover that in ferns they are controlling leaf development, in conifers they are controlling cone development; things like that. It's not as though these genes were invented in order to make flowers. They were pre-existing, and they were co-opted by evolution at the point where flowers started to evolve; and gene duplications probably helped in that process.



So if we go back to the Burgess Shale, back to the Cambrian, we find lots of onychophorans running around. And if you go to an Australian rainforest today, you will find onychophorans still running around, and they look the same. So 500 million years of evolution hasn't changed onychophorans. onychophorans are these neat, velvet worms. They are, by the way, viviparous. If you pick them up they squirt glue on you. They have their own neat little biology.



They are the ancestors of the arthropods. So what evolution basically did was it took an onychophoran and, among other things, it turned them into fruit flies, and butterflies, and horseshoe crabs and king crabs and lobsters and shrimp.



How do you do it? Well it was done basically by changing the range of segments in which particular things were expressed. If we go back here, you can see that the onychophoran has a lot of segments. It's got one leg on each segment. Okay? The fruit fly has many fewer segments and only six legs; the onychophoran has fifty legs or so.



So basically what was going on is that the HOX genes were used to say, "Oh, okay, now we're going to say that these segments become a head, these segments become a thorax, these segments become an abdomen. We're going to make antennae on the head, and we're going to make wings on the thorax, and we're going to make legs on the thorax, and the abdomen isn't going to have any wings or legs." Okay?



The way this initially happened--and you can find fossils that replicate some of these stages--you first make a generalized segment, it's got both legs and wings on it. Okay? You make it many times. So you've got both legs and wings on lots of segments. Then you restrict the range of expression so that only certain segments have wings, only certain segments have legs.



You do that by altering the domain of expression of control genes, and you use that kind of combinatorial specificity to say, "Okay, this is an antenna and not a leg. Okay, it's an appendage growing out of the body wall, but I'm going to make it into an antenna that's on this segment and I'll make it into a leg if it's on that segment."



So, of course, this goes on in seconds; evolution took hundreds of millions of years. So it's not the same process. Some of these HOX genes have retained incredibly conserved functions. In a famous experiment that was done in the 1990s, Walter Gehring's group in Switzerland, took Pax6, which is a gene that's shared by all bilateral organisms, and they genetically engineered fruit flies with an extra copy of Pax6--it is a gene that induces the development of eyes--and by turning this gene on, they were able to make that fruit fly grow eyes in unexpected places. Okay? So it could grow one on its--this is the regular eye; this is an eye growing on an antenna; this is an eye growing on a haltier; and so forth.



The interesting thing was that they could do this with Pax6 from a human or a mouse; in other words, the DNA sequence in the gene was so similar that it could be used to control the developmental pathway in an organism in which that gene had not been sitting for 600 million years. That's pretty remarkable.



Development is not easy to evolve, and I think this gets across one of the reasons that it's not easy to evolve changes in development. Every organism has to function and reproduce in order for a gene to get transmitted, and you can't tweak its development around too much or you'll make it fall apart. It's like you're driving down the road and you want to turn your Volkswagen into a Mercedes Benz, and so you get out your tools, and you're going sixty miles an hour, and you want to modify it, but you can't crash. Okay? So that causes constraints; there's only certain things that you can do while you're moving down the road.



These developmental constraints are not permanent. The genetic control of development does change more slowly than many other things, but I would submit to you that if we wiped out everything on the planet--let's first duplicate earth ten million times, and then let's go through and wipe out everything on all of those ten million planets, except for one species, and we leave it some food. Okay? It's the only thing that's there.



But on some planets all you've got is fruit flies. On other planets all you've got is redwood trees. On other planets all you've got is butterflies, and on other planets you've got albatrosses; but they have a food supply, they can live. Give them long enough, go away in your spaceship, come back, five billion, ten billion years later. I would submit to you that every one of those planets is going to have highly diverse life on it, and that many of the things that we see on this planet you will see on each one of those other planets.



They will contain a signature, probably a very interesting signature, of this huge disturbance that has been created on them. But I think that it's possible for redwood trees to evolve into squid. I just think it takes them a very long time. [Laughter]



The things that change slowly constrain things that change rapidly, and genes don't cause development by themselves. They're steering the dynamics of gene products that interact with environmental inputs. So the genes actually are a fair distance away, biochemically, physiologically, from the things they're controlling. They are working through complicated interaction systems.



So, a few take-home points. Development maps the information in genotypes into the material of phenotypes. It's like the process that occurs when a blueprint that an architect has drawn is turned into a building by the construction company.



Developmental control genes use combinatorial logic. There's a lot of other stuff that's really important in evolutionary developmental biology, besides combinatorial logic. It happens to be a pet topic of mine. You will find that if you talk to people who do this for their profession, that they regard combinatorial logic just as so natural, so much a part of the landscape, that they hardly feel the need to mention it anymore. But it is striking, when you compare plants and animals, that they both hit upon this method of controlling gene regulation.



The ancestors of currently existing organisms often had an awful lot of the genes that are now involved in controlling development. Remember that phylogenetic tree I showed you for the HOX genes. Many of them are present back in jellyfish, and certainly many more of them are present in worms and crustaceans and things like that. So a lot of what has gone on in evolution is changing the specificity of expression in time and space, and the specificity of receptors in time and space. Rather than necessarily evolving new genes that make new kinds of proteins, a lot of evolution has been concerned with making combinations of existing genes.



Interestingly, there is a very good evolutionary developmental biologist at Wisconsin. His name is Sean Carroll. He is a charismatic guy. And Sean has gone so far as to say that most of evolution, in the last 500 million years, has consisted of the evolution of gene regulation, rather than the evolution of new structural proteins. And, of course, by taking an extreme stance, he has managed to generate a controversy in which people are saying, "Oh no, it's not just that. There are all of these other new structural proteins that are going on." And this is always very good for one's scientific career, because both sides are increasing their publication rates.



Now, in fact, both things have gone on. Okay? But by having a controversy, people get motivated to pin down the details. So I am making a little bit of fun of controversies, but I also recognize that they are very strong motivating forces.



So next time, we're going to talk about the expression of genetic variation and reaction norms. And I want you to remember today's lecture, because today I have talked mostly about the big macro picture; the impact and the patterns of developmental mechanisms in the Tree of Life, in all plants and animals. And next time we're going to see what difference they make within single populations and in the course of the lifetime of single individuals. This is one way that microevolution connects to macroevolution; it connects through development. Lunch is possible if you would like it.



[end of transcript]

Reaction norms depict the range of phenotypes a single genotype can produce, depending on the environment. Reaction norms must fit within an organism's phylogenetic constraints. They can differ for different individuals within a population, but some traits differ very little based on the environment; some do not differ at all.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 7

Transcript



January 30, 2009



Professor Stephen Stearns: Today we're going to talk about developmental plasticity and reaction norms, and in the process we are going to complete our assemblage of all of the tools we need to understand microevolution, at least as a first sketch.



You'll recall that last time we were discussing developmental control genes and the way they lay down basic patterns in body plans. They provide insight into the deep history of developmental constraint and phylogenetic constraint, and they also set up patterns that then interact, during the course of development of individual organisms, interact with the environment to determine what the phenotype actually looks like.



The main thing that I'll be talking about today is the concept of a reaction norm, and in so doing I would like to fundamentally alter the way that you probably think about organisms. I want you to think about organisms, or about genomes at least, as having the potential to produce many different things. The actual thing that is realized depends upon the particular environments encountered, the particular history of that individual organism, and this can have profound effects on the way it looks, the way it behaves, and how long it lives.



So this completes our basic understanding of all of the fundamental processes that are operating in microevolution. And after this point we're going to go on to discuss major features of phenotypes, and on Monday we'll discuss the evolution of sex, and we'll go on to discuss things like life history evolution, sex allocation, and genetic conflict: all of those sorts of things.



So today I'm going to define a reaction norm. I'll tell you where it fits in the evolutionary process; where it came from; how it interacts with genetics; how you can actually visualize the simultaneous effects of genes and environment by making reaction norm plots. That's an important thing. There's been a long controversy in our general culture about Nature versus Nurture. Today I'm giving you the tool to take that issue apart and understand it rigorously. You will end up seeing that all aspects of all organisms are determined both by genes and by environment, and there are clear ways to think about it.



Then I'll show you how this kind of immediate, short-term phenotypic plasticity interacts with developmental control genes and phylogenetic constraints, and I'll do that with the butterfly wing, and we will see at the end that in fact biology is--heh, it's not surprising--biology is complexly organic, in a very deep way, and we can see that in the butterfly wing example.



So, this is what a reaction norm is. Okay? It's a property of a genotype. One can also define reaction norms for larger collections of things. You can define a reaction norm for a family, for example. All the sibs in a family might share a certain component of their reaction to the environment. But strictly speaking, a reaction norm is just the property of a single genotype.



So what it does is describe the set of phenotypes into which one genotype can be mapped, as the environment varies. So in the simplest case you have one trait and you have one environmental variable, and this is the way that that genotype, one genotype, would react to this one environmental variable.



Now, organisms have lots of traits, and there are lots of environmental variables, and so you can immediately see that this simple picture can be generalized into an N-dimensional reaction surface. It can get very complex if we're not just dealing about temperature, but say food, population density, presence or absence of members of the other sex, many things. And we think about that happening over the whole course of the organism's life; you can generate quite a complex reaction surface. So each genotype has the potential to end up anywhere along this reaction surface, depending upon the environmental history. So the study of reaction norms is intended to make that process explicit.



Now where's it fit? In the last lecture I gave you one slide that had on it, "This is what ecology and behavior do; this is what genetics does; this is what development does, in evolution." I am now repeating that slide, that basic message, in a diagrammatic context. Okay? So we can think of the evolutionary process basically as being a cycle that moves between genotype space and phenotype space. So this is one generation, this is another generation. And reaction norms develop at the stage where the genotypes that are present in the just fertilized zygote are being translated into the phenotypes of the adults.



When the gametes are then mapped into genotypes, to produce this array here--so when the zygotes are formed--this is the Hardy-Weinberg Law; this is basically population genetics up here. Down here, when the phenotypes that are being produced by the reaction norms then undergo behavior and ecology to determine a surviving set of organisms that can mate and reproduce and have babies, that's natural selection, down here.



Now the important thing is that all of these things go on in every generation. You can't get away from any of them. In every generation there's genetics, in every generation there's development, and in every generation there's ecology and behavior. So they're all necessary components of understanding the microevolutionary process.



This is the first picture ever made of a reaction norm. It was done by a German guy named Woltereck, working in lakes near Munich, and so he called them reaktionsnormen, not reaction norms. And what you see here are the morphological changes that are going on between generations--so this is a mother, this is her offspring, this is the offspring of this one, and so forth--within a single clone.



These are water fleas that are reproducing asexually. So what you're looking at is a series of different phenotypes that are all produced by the same genotype, the genotype is being copied exactly, and in the middle of the summer they are producing these helmets and spines.



There are a number of cases that are pretty well studied where this happens. There are spines, helmets and neck teeth in these water fleas, which are called Daphnia, and they are induced by dissolved molecules that are associated with predators, and the predator's efficiency in eating those Daphnia is affected by the production of those spines and helmets, on the Daphnia.



Making a spine or a helmet has a reproductive cost. So if the predator's not around, you don't want to make the spine, because it's costing you babies. So it is a contingent plastic reaction. You get a signal from the environment that says, "Oh, oh, danger. What do I do?" Well basically what you do is you modify the development of your offspring so that they're safer, but your offspring won't be able to have as many babies because they're better at not being eaten. There are bent shells in barnacles that do the same thing; they make them resistant to snail predators, but they reduce the barnacle's fecundity.



This cost is important. If the cost were not there, then the organisms would make the defensive structure all the time. If it was cost-free, why not do it all the time? Okay? But it's not, it cost them something, and so they're forced to compromise, and they try to minimize the cost of the defensive structures by not producing them unless they get a signal that there's danger.



Snails parasitized by castrating digenetic trematodes reproduce earlier. By the way, this digenetic trematode is also called schistosomiasis. So this snail is an intermediate host for a serious human disease. Let's take a look at these.



When Daphnia smell midge larvae, in the water--a midge larva is a little invertebrate predator that swims around and it catches Daphnia with its fore legs, like this, and if Daphnia makes a little neck tooth, it makes it harder for the midge larvae to handle it. Evidently this neck tooth actually, although it looks very small, cost Daphnia something, because they only make it when they smell midge larvae in the water.



This is a modern photograph of the helmet and the tail spine on Daphnia. You can see they're really quite dramatic. And this is where the cost is borne, here. You can see the number of eggs being produced, and there are fewer eggs in the body of this Daphnia than there would be in a mature member of this one. This one has actually just given birth, so its eggs are all out of its body.



In barnacles this is what it looks like. If the barnacle smells the snails, when it's growing up, it grows up in a clumped-over form. It bends as it grows, and instead of feeding freely out of the top of its body, it feeds very inefficiently, and it pays a price in not being able to make more babies. Barnacles, by the way, are essentially shrimp that swim around as larvae and glue themselves to the substrate and spend their lives stuck to the basement, kicking food into their mouth with their feet. So the feet of the barnacle would be sticking out here. Charles Darwin spent seven years working on barnacles, figuring out that they were actually crustaceans.



This is the data on schistosomiasis, and the neat thing about this experiment is that the reaction in the snail is induced just by water in which there have been parasites, not by the parasites themselves. In other words, you just give the snail a whiff, a little bit of scent that a parasite is likely to get into its body, and its reaction is, "Oh gosh, I am going to die from a parasite, so I better start reproducing." So it shifts its reproduction earlier in life; and you can see the extent of that shift right here. These are the ones that have been exposed to water with parasites in it; these are the unexposed controls.



So these things that I'm describing are all induced responses, they are all plastic reactions to signals in the environment, and they all shape the reaction norms of these organisms. So those are some concrete cases. Now let's look at sort of the abstract, visual, analytic framework a little bit.



Here is one reaction norm. I have sketched a common one for many poikilothermic organisms; many things that are--you would think of them as cold-blooded; they don't regulate their body temperature. The higher the temperature, the smaller they are at maturity. That would work--this general relationship describes how tadpoles grow, how many fish grow.



If you look at a population, it can be conceived of as a bundle of reaction norms. So there are many genotypes out there. So if we have a very small population with just about five or six genotypes in it--the green dotted lines are the individual reaction norms for the different genotypes, and there could be a population mean reaction norm. You just calculate the mean value across all the environments and all the genotypes, and that describes how that population responds.



This is important when you're trying to summarize this kind of complexity in ecology. You want to know how one population might react as the environment changes, so that you can analyze its impact on another one: a predator acting on a prey; a parasite acting on a host; a grazer acting on a plant. This is a good picture to have in your mind of what that population looks like.



Now traits can have very different expression patterns; it's not as though all traits have very dramatic reaction norms. And I just chose the example of five digits in many tetrapods, including ourselves, to indicate that you could have three different genotypes, and you could change population density a lot, and the number of digits on the hand wouldn't change. Everybody would have five fingers. There are some things that are just not sensitive to the environment. Okay? So think of the individual organism as a mosaic of sensitivities. Some of it is not sensitive at all to changes in the environment, or almost insensitive, and other parts of it are quite sensitive.



For example, fecundity. If you increase population density, fecundity will go down in individual organisms, because they're having to compete harder to get food. So if you restrict food, by any mechanism, fecundity will drop--and an increase in population density is one way to do it--and the genotypes in the population can react differently to that increase. In all three cases fecundity decreased, but genotype 1 was quite sensitive, and genotype 3 was much less sensitive to the shift in population density; and that makes a difference.



As a matter of fact, if you think about it, right here, if you have a fluctuating population, and this population is going between low density and high density, you have a method of maintaining genetic variation right there, because the reaction norms cross, and the guys that were good at one density are lousy at the other. So if the population cycles back and forth between them, one time G1 is favored, the next time G3 is favored, and so forth. Okay? So I'm trying to develop the notion that by sketching reaction norms, you can come up, very quickly, with a useful analytical picture of what's going on in a population.



For example, if you have this sort of a reaction norm pattern for four genotypes, and you select upward here, you're going to lead to no response over here at all, because they all happen to converge at this point. So selection here doesn't make any difference to what you observe in this part of the environment. But in this case, the crossing reaction norm case that we had in the last picture with fecundity, if you select upward in this environment, you're going to have a downward response here.



If we select at low population density, and population density is low for a long time, it's going to produce a shift in the population over here, because G1 will be favored, and it has low fecundity at high density. Okay? That's this situation.



We can just look at a sketch of a reaction norm and we get a sense for how sensitive that trait is to changes in the environment. This is not a very plastic trait, it's pretty insensitive, and we can see that because it has a shallow slope. This trait's very sensitive. You change the environment a little, it changes a lot.



Now it's not just spines and helmets that have reaction norms. This is a picture of an Affymetrix GeneChip for Drosophila melanogaster--it's got 13,500 genes--and what the chip is doing is it's picking up the messenger RNA, which is being expressed in the organism; and the intensity of light that you see at a given spot is a measure of the concentration of messenger RNA for that particular gene. So in one picture you have a summary view of the output of the entire genome. Okay?



These things have reaction norms. I put this in for Andrea. Okay? Andrea just wrote a paper about this. So these things have reaction norms. If I gave you Drosophila and I exposed them to high temperature and low temperature and you extracted their mRNA and you ran them out on a GeneChip and you compared the two patterns, you would see big differences in the patterns of all of those light spots. And if you did that carefully, you would be able to draw the reactions of the expression patterns for all the 13,500 genes in the genome. So these concepts are general. They're not limited to morphology. They apply to any aspect of the phenotype, and this is now a very popular way to measure phenotypes. Okay?



There are lots of things like GeneChips out there. How many people in the audience know, or have heard of GeneChips, or other methods of measuring outputs? You're not quite densely scattered enough to have you turn to everyone around you and explain what they are. [Laughs] If I had about twice the density, I could just stop talking and have you all explain to each other what a GeneChip is. Okay. We can leave that for a later date. Suffice it to say that in modern molecular technology these things, which are now just about ten years old, a little over ten years old, are methods of looking at the expression of all the genes in the genome all at once; and they too have reaction norms.



So to sum up on reaction norms. A reaction norm is a description of how genes are mapped into the phenotype as a function of the environment. They are properties of genotypes. So if you really want a proper, rigorous way of measuring a reaction norm, you have to be able to clone the organism, so you can get the same genotype replicated and then test it in different environments. If you wanted to do that for humans, what kind of data would you use?



Student: Twins.



Professor Stephen Stearns: Twins. What kind?



Student: Identical.



Professor Stephen Stearns: Identical twins. Identical twins are probably the only--I suppose there might rarely be, these days, identical triplets. I suppose there might even be, somewhere in California, identical octuplets. But most of the time we deal with identical twins, and that's about as far as you can go, in humans, with this sort of thing. But in Daphnia, or in plants, it's possible to get genotypes replicated, up to a hundred individuals sometimes, and then you can make a very accurate measure of a reaction norm.



You can think of a population as a bundle of individual reaction norms; and that's an important concept because when we come to ecology we're going to be thinking about how predators interact with prey, and about how competitors interact with each other. And when we do that, normally the way that biologists have done it in the past is they've chunked those things as species, where they have a species typical property. Okay? So all the species 1 are supposed to behave one way, and all of species 2 are supposed to behave another way.



But the differences between the individuals in those species are really important, and when the two species are interacting, it's not like they're all identical individuals interacting. They are different, and when the species interact it's bundles of reaction norms interacting with bundles of reaction norms. And this produces important effects. For example, it tends to stabilize ecological interactions. So remember that for say about six or eight weeks down the line, when we get to ecology. This property of populations has important consequences.



There's a real easy way to talk about the sensitivity of phenotypes to the environment. You just make a reaction norm plot and look at the slope. If the slope is steep, those organisms are very sensitive to changes in environment; if it's flat, they are not.



And in terms of the kinds of intellectual tools that one might pick up in the course of a liberal arts education, in order to deal in later life with the claims of people who want to talk about the evolution of IQ, or racial differences, or lots of stuff that involves assumptions about genetic determination, reaction norms are useful because they visually describe the contributions of genes and environment to the phenotype. And, for example, I will put up a speculative plot, just to illustrate the potential social significance of what I'm talking about.



If, for example, I put IQ up here and I put Family Annual Income down here--already we're in trouble, right; we're not being politically correct anymore--and then I do this, basically what I'm saying is that if I took human identical twins and I raised one here and the other one here, I could get that. Okay? And what that shows you--by the way, I don't know that that is true; I'm just trying to give you something to remember, that will convince you that this sort of analysis can potentially be significant--what that shows you basically is that people might appear to be real smart in one environment and stupid in another, compared to the other ones in the populations, and that these things are context dependent. So, that's just an illustration of this point down here on the bottom.



Okay, so I've been talking a lot about phenotypic plasticity, and I've shown you these wonderful examples of Daphnia reacting sensitively to predators and so forth. Does that mean that organisms are really plastic? Can I just pick up a bunch of clay and mold it into anything that I want, depending on the environment that I expose it to? No I can't.



And that's because, as we learned last time, the large-scale structure is determined by things that are hard to change, and those are developmental patterns that have a deep evolutionary history, and they set up a rigid framework within which the plasticity is expressed. So the things that change slowly--those are the developmental control genes--are constraining the things that change rapidly. I just lost a little bit of text off the bottom.



So let's do this with the example of Distal-less. Distal-less is a developmental control gene. The pictures here basically are showing you how the Drosophila larva gets set up very early in development. The first thing that happens is that an anterior/posterior axis gets laid down. That's done by the Hox genes. Then the dorsoventral axis is determined by Sog and Chordin and Decapentaplegic and things like that.



Then, after the basic axes of the organisms are laid down and segments are formed, other things turn on that determine whether you'll be dealing with a head, a gut or a tail. Interestingly, the name for the gene that induces heart formation is Tinman, from the Wizard of Oz, who didn't have a heart. Okay? So they give neat names to some of these things.



And what we're worried about today is this gene here, Distal-less, which determines body wall outgrowth. Remember last time I also showed you that picture of Pax6; that's the gene that induces eye formation. But today we're going to talk about Distal-less. And if you look at the body of a fly, this is where the action of certain mutations takes place. If you get mutations in Distal-less, these are the parts of the body which are going to be affected. They are all extremities, all out-pocketings of the body wall, which are then being developed into antennae or mouth parts or legs. Vestigial is working on wings and haltiers, and Eyeless is working on the presence of eyes. Okay?



Now in order to tell you about this deep developmental constraint in butterfly wings, I first want you to notice that there's something that's called a Nymphalid groundplan. The Nymphalidae are a large family of butterflies, and in the nineteenth century German biologists, with German thoroughness, out to eight decimal places, did an exhaustive study of thousands of butterfly wings, and they were able to take that whole family of Nymphalidae, with its hundreds of species, and reduce them all to variations on these themes.



So they found that in the middle of the wing you could have stripes; in the outer part of the wing you could have what they called border eyespots, or border ocelli; right on the edge of the wing you could have bands, and so forth. So that this would describe all of the different kinds of things that you could do with butterflies. And we're going to focus on the eyespots.



Now this is the diversity of butterfly wing patterns that you can get in about ten minutes in the Peabody Museum collections. They are beautiful, they're just amazing. I remember the first time I saw a birdwing butterfly in the collections at the Bishop Museum in Honolulu. The birdwings come from New Guinea and other parts of Southeast Asia. They're about that big. They're the largest butterflies on the planet. And actually their form is a bit like this guy, except they're about four times bigger.



And you can see that simply by varying the location where colors are expressed, and by varying the size of the different elements, you generate a huge number of patterns. You can even use them to write numbers on wings. Evolution has written numbers on the back wing of this particular butterfly; this is an '89 butterfly.



The model system in which this is best studied is in a butterfly called Bicyclus, and it has been worked on by Paul Brakefield in Leiden, and Sean Carroll in Madison, Wisconsin, and Antonia Monteiro in our department, and a number of other people, Vern French in Edinburgh. And Bicyclus has a number of neat features. One of them is that it is developmentally plastic.



In the wet season it looks like this, and in the dry season it looks like this. And, in fact, these are two brothers who have been produced in the laboratory, with this one being raised under wet season conditions and this one being raised under dry season conditions. So one genotype can elicit a range of phenotypes, and you can see that in the process the eyespots change considerably in their size and intensity.



Now it turns out that you can fish the Distal-less gene out of Drosophila, and you can use that segment of DNA to recognize the homolog gene in the butterfly, and you can then put a reporter onto the homolog, and you can ask that gene to express its reporter when it's being expressed, so that you can see visually where the gene's being expressed. When that's done, you can see that every place that an eyespot is going to form in the adult wing, you can see the gene being expressed in the wing disc, in the developing pupa.



The way that butterflies and flies and other holometabolous insects develop is that after the caterpillar or the larva has fed for awhile, and it's starting to form its pupa, the cells reorganize in the pupa, into structures that are going to be parts of the adult, and the wing disc, that's going to be the wing in the adult, looks like this in the pupa, and it's sitting right on the surface of the pupa.



So that if you want to do developmental biology experiments on it, you can go through the wall of the pupal case and you can pick out a few cells and you can move them around. So, in fact, you can go in and cut one of these things out and put it down somewhere else; if you do, it will make an eyespot there.



So this is actually an exceedingly neat system to work in because you can actually do cell manipulations, as well as genetic manipulations. You can manipulate both the developmental biology and the underlying genetic structure, in butterfly wings.



This is another species; it just has two eyespots, and when you look at its wing disc, it just has two places that Distal-less is being expressed; and those are going to be right in the center, right where that white spot is.



So Distal-less is actually telling the wing disc where to make eyespots, and the Nymphalid groundplan says you can only make those eyespots in certain places. And the Nymphalid groundplan, the butterfly wing groundplan, is arguably about 100,000,000 years old; it's ancient. So does that mean that you can't change the eyespots? No it doesn't.



Almost everything about the eyespots has a reaction norm, except their location and number. Within a given species you're always going to get the same number, and they're always going to be in the same place, but whether they're big or so small that you can't even see them depends on the environment in which they're expressed.



So if you raise a whole bunch of families, and you compare the siblings across families, to make reaction norms, you can see that the diameter of the white part of the spot and the diameter of the black part of the spot changes as you go from low to high temperature. You have low temperatures in the dry season and high temperatures in the wet season, and that shifts the reaction norms on the butterfly wing.



Well I'm a sucker for analogies, and analogies are dangerous. You might think that the eyespot was a vase, and into that vase you're going to stick a bundle of reaction norms. And you can think of the vase as being the phylogenetic history of the developmental constraint on the butterfly wing, and it's holding those reaction norms within a certain range, but that the environment then is allowing them to vary, to the degree that a bundle of flowers could flop out of a flower vase.



Well it turns out--I'm sorry for this; this is something that I checked this morning and it wasn't going on. At any rate, I'll read this out for you. Can we think of macroevolution as having constructed a vase, within which the reaction norms sit? And the answer is no.



And the answer is no because some of the genes that are controlling the shape and the position of the eyespots--so things like Distal-less--are also involved in determining the slopes and the shapes of the reaction norms. These two things are genetically entangled, and their entanglement is a case of the same gene having two different functions at different times in development, and natural selection will operate on it throughout the lifecycle.



So it's not as though there are some things that are constraints, that are not being changed, and there are other things that are genes that are sort of tweaking the constraints a little bit. In fact, the same genes are involved in producing both things. So if we want to shift the slope of the reaction norm by selecting on phenotypic plasticity in Bicyclus, we are going to be selecting on genes that are also determining the location and number of eyespots.



If you think this kind of stuff is nice, you can go and look on the Web, on these sorts of websites. Antonia works on butterfly wing patterns. Gunter works on the tetrapod limb, and with Vinny Lynch he has recently been looking into the origin of the mammalian female reproductive tract. So they have been comparing things like duckbilled platypuses and spiny echidnas--which are mammals that lay eggs--with kangaroos and eutherians--which are mice and lions and things like us--and discovering where it is that the mammalian female reproductive tract actually came from. It turns out that the HOX genes are involved in that, and that it's another one of these stories of gene duplication making the development of new structures possible.



Rick Prum, who's our department chair and works in the Peabody Museum, is one of the world experts on feathers and on the fact that dinosaurs had feathers, and if you're interested in working with Rick, you can certainly drop in, and he's a very friendly guy and would be happy to show you what he knows about feathers. So this is an active area and it produces a lot of fascinating research.



To summarize my overview of it, what I want to emphasize is that the phenotype, the whole organism that you see, and the whole lifecycle of that organism that you see, is a mosaic of parts, and their pattern of determination varies tremendously in evolutionary age. So if you just look at my own body, the parts of me that are extremely old are the fact that I have four limbs and five fingers, and the parts of me that are evolutionarily relatively young are the size of my cerebral cortex and some other aspects of me.



And if you were to look into the plasticity of my cerebral cortex, you would discover that it is incredibly plastic, and that when I am a little baby and I'm just born, I have billions more connections in my nerve cells than I do when I'm seven-years-old, and that a great deal of my mental development, between birth and the age of seven, has essentially been the remodeling of my cortex by plastic interactions with the environment. And in fact that's what a lot of learning is about; it's about plastic response to environment. So I am myself, as are you, a mosaic of things, of very different evolutionary ages.



The basic developmental patterns that we see in animals are mostly about 500,000,000 years old. In plants they're a bit younger. The HOX control of body symmetry and body pattern in animals is arguably about 600,000,000 years old; maybe a little less, maybe 550,000,000. The ABC pattern of flower development in flowering plants is probably somewhere between about 95 and 135,000,000 years old; that's something that happened in the Cretaceous.



Now let's shift timescale and go down to one generation, one organism, encountering a specific environment. Its plastic reaction to the environment has evolved relatively recently, and it implements specific contingency plans. Daphnia that come from lakes that do not have fish in them and haven't had fish in them for a long time, don't react when you put the smell of a fish into the water. The Daphnia that come from lakes that have had fish in them for along time react, and react strongly and quickly. So the plastic reaction is something that can evolve.



I want to caution you though, it is not as though all the fine details of the plastic response are adaptive; they are not necessarily all adaptive. For example, think about temperature. If we are studying the plastic reactions of organisms to temperature, it may very well be that things that live in the Arctic have a different reaction norm than things that live in the tropics, because they've encountered a different temperature regime, and that that's an evolved reaction. But it's also quite possible that it's just biophysically impossible to do something when it gets colder; that doesn't have to evolve.



So I want you also to be able to think of the necessity of taking something like a plastic reaction norm and dissecting it analytically so that you can figure out what part of it's adaptive and what part of it is just there because that's the kind of stuff that organisms are built out of. They are biochemical systems, and biochemistry, we know, has reaction rates that change with temperature and with a lot of other things. Okay? So it's not--this is not all adaptive.



The thing you actually see, the organism you analyze, is just one point on a multidimensional reaction surface. It could have been a lot of other things, and all those other things that it could have been are important when we think about evolutionary ecology, when we think about population dynamics, when we think about interactions between hosts and parasites, because they represent all those other potential interactions that could be going on in other circumstances. Okay?



So by thinking about reaction norms, we can both express the genetic variation in the population; we can express the developmental reaction to the environment, the way all of those different genetic combinations will react to the environment; and we have the potential to visualize the dynamic over generations, as both the gene frequencies and the environmental circumstances change. So there's a potential here for a lot of interesting analysis. I think the basic take-home point though is this one.



Every phenotype is the product of both genetic and environmental influences, and the way they interact to produce the phenotype is extremely important. So it is almost never the case that you can claim that only Nature, or only Nurture, accounts for what you see in organisms.



So that basically completes what I want you to know about microevolutionary principles, before we now go into the analysis of how natural selection shapes phenotypes for reproductive success. I'm going to use all these concepts. For example, when we get to the evolution of age of maturity, I'm going to talk about reaction norms for age of maturity in human females, and in fish, and in mammoths. So I want you to remember these elements.



I also want you to remember, as we go forward, that everything that you see in organisms has an evolutionary history. It doesn't have to be an adaptive history. It might be drift. Things might happen in phenotypes that are byproducts of stuff that's going on somewhere else in the organism. There are all kinds of alternatives that you should be continually prepared to compare, when you're trying to analyze what you see, but everything that you see has evolved. All you have to do to see that is remember at one point your ancestors were bacteria, and everything else has come since then. So next time we're going to start talking about how organisms are designed for reproductive success; and our first step is why do they reproduce sexually?



[end of transcript]

There are several explanations for the evolution of sex and its continued prevalence. One is facilitating the spread of helpful mutations while hastening the removal of harmful ones. Another is expediting resistance against pathogens. Sex does have several costs compared to asex, such as only giving half your genome to offspring, having to find mates, and the risk of predation and STDs. Overall, the benefits outweigh the costs and sex has a firm hold on the majority of the recent branches of the tree of life.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 8

Transcription



February 2, 2009



Professor Stephen Stearns: Now before I get going on today's lecture, which is about the evolution of sex, I thought that I would just share this picture with you, which I took at ten o'clock on Saturday morning. These are the Hamden Golf Course turkeys, and they sometimes show up in my backyard, and they're absolutely remarkable creatures.



If you look at them, probably the first thing that strikes you is how do they make those iridescent colors, and is there a different way perhaps that they make the color in their neck, or perhaps on their face? Their neck is red and their face is blue. Is that biomechanically different? In fact, these colors are a diffraction gradient. There's no dye in them at all, and the colors in the head, the blue color, is actually made by kind of a fractal matrix of bubbles. The red color I think is a dye. So there's some weird stuff going on in the way that turkeys make colors.



Why the heck do these turkeys look like this? Well the standard explanation for that, which may or may not be true--it hasn't been tested too explicitly in turkeys, although it has in pheasants and in peacocks, which are both related to turkeys; they're all in the family gallinaceae--is this is the product of sexual selection, and that what you're looking at is what the female brain of the turkey finds attractive. Well there's a deep mystery in that. Why should something that a female turkey thinks is beautiful also elicit the sensation of beauty in my brain? I last shared a common ancestor with a female turkey about 150 million years ago. Has the perception of beauty persisted unaltered in both lineages for 150 million years? So you see the contemplation of turkeys in the snow can take you a long way.



Now today I want to talk about the evolution of sex, which will eventually get us to sexual selection in a bit over a week. And in so doing the messages that I want to get across are that this is first a fundamental question in biology, because it shapes almost everything that we study in biology. Sex, in the sense that I'm going to use it today, in terms of organized diploid sex, has been around probably for about one and a half billion years, and it's had many, many consequences.



There is a puzzle about sex, and we will see that it is complicated and costly, and therefore it needs an explanation. I think it was the Marquis of Chesterfield, or someone like that, who on advising his son on the con--on the issue of sex said, "It doesn't last very long and it's extremely expensive." [Laughter] And we will look at some of the consequences of sexual reproduction for large-scale patterns in the plant and animal kingdoms.



Now I need to set this up by distinguishing between recombination, reproduction and gender, because the word sex often elicits in the minds of non-biologists a composite of all three things. Recombination is the process that causes offspring to differ genetically from their parents and from each other. Now there are some exceptions to this.



For example, armadillos always have identical quadruplets, which makes them convenient for some things. Identical twins in humans, of course, are an exception, where the recombination has made them different from their parents, but they're still identical to each other, and that is because they derive from an early mitotic event in development; so they were originally the same zygote. And then we have the extravagance of polyembryonic wasps where a parasitic wasp lays a single egg into a caterpillar; the egg starts to develop into a blastula; the blastula fragments into hundreds or even thousands of pieces, each one of which then develops into an embryonic wasp.



Some of those sister wasps differentiate into warrior castes and go cruising around the caterpillar, wiping out other wasps that may have laid their eggs into the caterpillar. They don't make it, they die, but they clear the way for the others, that then eat up the caterpillar and hatch as wasps, out of the caterpillar. So there are always fascinating biological exceptions to the idea that recombination makes siblings different from each other. In some cases they are not, but normally they are.



Reproduction is not the same as recombination, and we can see comparatively, through these contrasting examples, why it is that recombination and reproduction are not always necessarily coupled. In us they are, but if we look at bacteria and clonal plants, we can see that they can reproduce without recombining. And bacteria can actually arrange to have sex and not divide at all. They can undergo a recombination event and simply change themselves genetically, and then wait for awhile and divide later.



And, of course, in plants, clonal plants have the option, many of them have the option of either producing asexually or sexually. Often they produce sexually in the parts of them that will then disperse to another place, and asexually in the parts of them that will stay here; here being more predictable than there.



Gender is something that is really not at all the same as recombination or reproduction. Gender is maleness and femaleness. So it's all of the secondary sexual characteristics of the two genders. And that is something that originated with the production of gametes of different sizes.



That didn't happen until after meiosis originated in evolution, and it then created a situation in which sexual selection could occur; where there was one kind of selection on things that made lots of small gametes--sperm--and another kind of selection that operated on things that made a few large gametes--eggs. So those are three different things.



I also need a few words, and I'll refresh your memory or introduce them to, depending on where you're coming from. Isogamy means that we're dealing with a species in which all of the gametes are the same size. That happens often in the protists, in unicellular algae and protozoa, that they produce gametes of the same size. Anisogamy comes where there are gametes in two different sizes, the big ones being eggs and the small ones being sperm. So anisogamy is the condition with which most of you are familiar. Syngamy means fusion of gametes to form a zygote; that is one step in the process of sexual reproduction. Karyogamy is fusion of the two gametic haploid nuclei. So the gametes come together, and then after that happens their nuclei fuse. And these things take time. We will see that those actually are some of the--the time they take is some of the cost of sex.



Now mating types occur at this stage, with isogamous organisms, and they reduce inbreeding. Mating types are common in many unicellular algae and in many ciliates, like Paramecium. They are basically a situation where the organisms of one type can only mate with organisms of another type. So if you are mating Type 1, you can mate with mating Type 2 but not with mating Type 1. This, in some sense, is genetically analogous to having a large number of sexes in the population, but with a rather interesting pairing rule, that you can only not mate with people like yourself. The population then differentiates and evolution produces a huge number of mating types.



Now the traditional view on why sex exists was formulated by August Weismann and then elaborated by Mueller, and clarified by Crow and Kimura, and it goes like this: recombination is there in nature basically because it increases the rate of evolution, and it does so in two ways. It increases the rate at which two advantageous mutations can be brought together, and it increases the rate at which disadvantageous mutations can be discarded; and I'll illustrate that with a few diagrams in a minute. A consequence of this is that it decreases the probability of extinction. All of that is true, but it may not be why sex exists.



So here is the traditional view. In a large population, if we contrast a large asexual population with a large sexual population, you should think of the vertical axis as being the frequency of a mutation in the population and the horizontal axis as being time, and A, B and C are beneficial mutations that are arising at different places in the genome. They're not alleles with a single locus. They are three different genes whose combination it would be really cool to have, because it's going to improve reproductive success, defend you against diseases and so forth.



In the asexual population, first A pops up and it takes over the population because it's advantageous. Then C, which had occurred once before but not in combination with A, happens sequentially in the same organism that's already gotten A. So in the asexual population the advantageous mutations have to happen one after another, in a descendant lineage, because there's no sex to bring them together. AC dies out because shortly after it arose, AB came along and AB was preferential to AC, and then eventually C arises in an organism that already has A and B, and ABC takes over. That's a process of clonal interference.



In the sexual population these mutations can be conceived of as occurring at just about the same time as they did in the asexual population, but they are rapidly brought together by sex and recombination, and the combination ABC spreads through the population much earlier, achieving fixation here rather than here.



Now if we look in small populations, the advantage of sex is not nearly as great. Can anybody tell me why? You can see a picture there, but can you interpret it in an English sentence? Why is it that in the small population the advantage of sex is not so great? It still can be advantageous, but it's not as great as it is in the large population.



Student: You have less animals.



Professor Stephen Stearns: Population's smaller, yes.



Student: You have less animals for [inaudible].



Professor Stephen Stearns: Somebody want to help Brett out? He's looking for a word. Yes?



Student: Small population, less genetic variation.



Professor Stephen Stearns: There is less genetic variation in the small population. Yes. Why?



Student: It's a lower population count, [inaudible].



Professor Stephen Stearns: Where does variation come from?



Student: Mutations.



Professor Stephen Stearns: Mutations. Yes. You can think of the population size, all those genomes out there, as being a net that catches mutations. The smaller population is catching fewer of them, and therefore there are fewer things that it could bring together, and therefore it takes a longer time in the small population for sex to become advantageous, because it has to wait for that mutation to come along. In the large population, it's there very quickly, relatively quickly.



Okay, now about the costs of sex. In an isogamous organism the costs are genome dilution, the amount of time it takes to have sex, and the risk of predation, of sexually transmitted diseases and of the difficulty of finding mates. So let's step through those.



The cost of genome dilution basically is that by engaging in sex you've made a decision that your offspring will only have 50% of your genes, and it's going to have 50% of somebody else's genes; whereas if you were asexual it would be 100% your genes. Okay? So that's what we mean by the cost of genome dilution. And I think that you can see, if you work through it, that this is indirectly also the cost of having males.



You don't really need to have males at all, if you're asexual, do you? As a matter of fact, we usually think of asexual species as consisting only of females, and the reason for that is that they make eggs. Okay?



Now you can look at yeast, which can reproduce either sexually or asexually, and experimentally measure this difference between one hour for asexual reproduction and eight hours for sexual reproduction. So let's do a little mental experiment here.



We start off a vat of beer, and we seed it with one asexual and one sexual yeast organism, and they happily go to work starting to make beer for us. After one hour, we have two of the asexual, and we still just have one of the sexual, don't we? After two hours, we have four of the asexual; we still only have one sexual. After three hours, we have eight of the asexual; we still only have one of the sexual. You get the idea.



That timing difference has an enormous impact on the relative fitness of the two types. Just because it can reproduce faster, the asexual type is going to sweep through that population and competitively exclude the sexual type; all other things being equal. So we essentially end up with a glass of beer that's produced almost 99.999% by asexual yeast.



The other cost, of course, is that if you have to go find a mate and take time to mate, you expose yourself to being eaten by a predator. In the process of mating, any kind of disease that mate has could jump into your body or into your offspring. It could be a selfish genetic element that got into your offspring, coming in through the genome of your mate. And it's pretty hard to find mates at low population density, which is why we find that asexuality, for example, increases in frequency as we go into the deep ocean. And if you look at the organisms that are specialized on eating the carcasses of dead whales, which drop onto the ocean floor infrequently and at great distances from each other, you discover that they have a higher rate of being asexual, or being simultaneous hermaphrodites, than do things that say live on tropical reefs near the surface at high population density.



Then if you have anisogamy, in its simplest form, the cost of males is a twofold cost. So if you're a female and you have the option of being asexual, and you're wondering, "Should I be sexual?" and you ask yourself, "What's it's going to cost me?", basically if you count through to the number of grandchildren you have, you'll have twice as many grandchildren, if you don't make any males--if you only make daughters you'll get twice as many--through your female line, bringing--and this is because also the genome dilution effect is coming in. Okay? So anisogamy, plus genome dilution, gives you a twofold cost of sex.



This word Acarophenax is going to come up several times, because it's a spectacularly perverse mite, and we all are interested in spectacular perversion. So Acarophenax is a mite that has an extreme example of local mate competition. And has anybody already run into this example? Can you tell me what it is? Mites, many mites, not just Acarophenax, lay their eggs into their abdomen, where the eggs hatch out inside the mother, and the brothers then impregnate their sisters, inside the mother, and the brothers die and the sisters eat the mother. That's pretty spectacularly perverse.



The question is, if you are the mother, how many sons should you make and how many daughters should you make, in order to get the maximum number of grandchildren? Okay? And we will run through this when we have the Sex Allocation lecture next week, but I just wonder if any of you can anticipate that. Here you are, you're the mother mite. You want to maximize the number of your grandchildren. You're not worried about getting eaten, because your kind have always had that, that's just a normal part of life. The only issue that occupies you is how many sons should you make and how many daughters should you make? You're a little bit worried about the lady next door and what she might be doing. Any idea?



Student: Only one son.



Professor Stephen Stearns: You only make one son, and that's because that one son can make enough sperm to inseminate all of his sisters. And if you made two sons, you would have some sperm that was going to waste, and you could've used that egg to make another daughter that got inseminated. That is, in fact, the solution chosen by Acarophenax and all such similar mites; one son, many daughters.



Now to go back to this slide, just to remind you. I've been telling you lots of interesting natural history, but the point of it that sex is costly. It takes time, it dilutes your genome, and if you are anisogamous it costs you everything that's involved in making sons, who otherwise might be irrelevant if it weren't for whatever advantage they might bring in with sex.



So the paradox of sex is basically that's it regular, complicated and costly. And, as I indicated with the example of the yeast in the brewer's vat, asex should rapidly take over sexual populations. Nevertheless, when we look at the Tree of Life, we see that the majority of organisms are sexual, and even the ones that we think of as being asexual, like bacteria and viruses, in fact have evolved something like sex. So it seems to be a good thing.



We've got this traditional explanation that sex speeds up evolution and reduces extinction probability. But it has a problem. It is couched at the level of the species or the group. Okay? And it's not strong enough to maintain sex against the invasion of asexual mutants. The reason is that if you think of it in terms of being good for the species because it causes the species to last a longer time before it goes extinct, well the generation times of species are orders of magnitude longer than the generation times of individuals.



Vertebrate species last usually one to ten million years. Individuals last months to years. So about 106 difference in how fast things happen at the individual and the species level. So any individual advantage--for example, asex--could be multiplied thousands or millions of times before the group or the species advantage of not going extinct so frequently could take effect.



The individual advantage of asex seems to be roughly twofold each generation, and that adds up to a big difference over a lot of generations. So asexual mutants should always be taking over. But they don't.



Now before I go into the solution to that problem, I want to give you a little bit of what we think is the evolutionary sequence in matters sexual. In prokaryotes, bacteria and archaea, probably the repair of ultraviolet damage to DNA was very important. Then mitosis originated and eukaryotic cell division. So once the eukaryote ancestor formed, with the proper cytoplasm and nucleus, and we had multiple chromosomes, mitosis originated. We're back about probably 1.5 to 2 billion years here.



Then meiosis, which is really a very, very complicated symphonic arrangement, originated by a duplication and modification of mitosis. Then only after we had mitosis did we get isogamous mating types, and then we had the evolution of anisogamy. Now the evolution of anisogamy is actually a big deal because it is what eventually led to the differences between males and females. So sexual selection only starts to happen after we have things that make gametes of different sizes. So the ideas about why that happened are kind of interesting, because they're right at the origin of male/female difference.



One of the ideas is that a bigger egg would improve offspring survival. So some of the individuals in the population, in the isogamous population, might be under selection to produce bigger eggs, because they could then have babies that survive better. They could also produce more pheromones. So they could advertise, so those eggs could advertise their presence better. A bigger egg is a better perfume factory. So you should think of eggs as being big, fat perfume factories. Okay?



Once this--and this is now frequency dependent selection--once some of the organisms started to make bigger eggs, the others, some of the others, could decide, "Oh, I don't need to make a big egg and invest a lot of energy in it because somebody else is doing that for me; instead I'll try to inseminate lots of eggs." And they got selected to make sperm. Okay? So they made many small gametes that could swim fast and were good at detecting perfume. That's one idea.



Another idea on anisogamy is that those big eggs have got cytoplasmic organelles, and those cytoplasmic organelles have got their own independent genome in them, that they had when they came in as mitochondria or as chloroplasts or as spindle apparatus. And you don't want to generate a situation in which you have competing cytoplasmic genomes, because if you do, you get an uncontrollable evolution, microevolutionary process going on in the cytoplasm that can cause the takeover of the cytoplasm by a basically selfish mitochondrion or a selfish chloroplast.



There are, in fact, mitochondrial cancers. There are cases in which mitochondria get out of hand and you end up with cells that are just packed wall to wall with mitochondria. You don't want that. You want to have the cell to be a relatively well regulated, well biochemically balanced environment. So one of the consequences of biparental inheritance, where you are only getting your organelles from one of the parents, normally the female, is that you avoid conflicts. Okay? This may or may not have been important at the origin of anisogamy, but it is certainly one of the reasons for its maintenance.



And before I go into mutations and parasites, let's recall something that August Weismann said back in 1892: "Sex has a huge number of consequences." It's been around for a long time, and so when we try to detect why sex originally evolved, we're dealing with a situation in which the original reasons are concealed by lots of layers of adaptations that have built up since then.



So we have to clearly distinguish between causes and consequences of sex. But this is now very hard to do because the original causes are now covered up with so many of the secondary consequences. People have been repeatedly fooled by confusing consequences for causes. In a sense I suppose the bottom line on that slide is we actually are in a position were we can talk intelligently and we can do science on the reasons for the maintenance of sex, but we have difficulty--and may always have difficulty--in identifying the real reasons why sex originated, because that happened a long time ago, in a different situation, and it's had all kinds of consequences.



Okay, so what kinds of forces maintain recombination? When Alex Kondrashov wrote a paper about this about, oh gosh, it's fifteen years ago now, he came up with forty-three, and I'm only going to list a few. I'm only going to list the ones that I think remain plausible and can be demonstrated experimentally or comparatively. However, I want you to be aware that if you decide to write a paper on this, and you want to know what are all the reasons that people have given for the origin and maintenance of sex, that the list is on the order of forty or fifty hypotheses.



There are two important genetic hypotheses. One is repair and the other is mutations, and in a sense mutations really are an issue of repair at the level of the population. And there are ecological hypotheses. Parasites and pathogens, and the co-evolutionary problem that they pose, are accepted by many now as a major reason why sex is maintained in populations. And it is also true that recombination spreads risks and hedges bets in ways that go beyond the issue of whether your children are going to be infected by a particular pathogen. You can deal with all sorts of ecological situations. So you can think of the reasons as falling into two general categories: genetic and ecological.



So back in prokaryotes, a lot of repair mechanisms were evolved, and they are sophisticated. They're still in operation; they're readily studied in microbiology laboratories. DNA polymerase itself does proofreading. If a nucleotide has been excised and is missing from the sequence, then you can use the complementary strand to patch it in. So that happens, and that needs a double-stranded DNA, not a single-stranded RNA. So if you're just dealing with a single-stranded RNA virus, it may very well have difficulty doing this kind of repair, and has a very, very high mutation rate. I want you to remember whenever I say mutation, that it is often a problem of inadequate repair. So the repair mechanisms actually control the mutation rates.



In eukaryotes we have this kind of proofreading, and we've got a lot more. There are some repair mechanisms that actually need diploidy. So you have a whole extra chromosome. You have two double-stranded DNA molecules, and you can go to the alternate as a backup. So you can use that to repair any mutational damage.



But the most interesting kind is recombinational repair; well let's put it this way, to somebody who thinks at the population level, the most interesting kind is recombinational repair, and that is because it isolates the defects on a subset of gametes. You can have mutations in five or six genes. Recombination could put them all into one set of gametes, and if those gametes die, those mutations are gone. So recombinational repair isolates and throws away, through natural selection, the defects in the genome.



There is a concept here that I want you all to absorb and understand, and it has to do with the way that mutations will accumulate in small populations that are asexual. And it's important because it can be shown that this idea is at least theoretically true--it can be demonstrated experimentally in small populations--and it is a serious, long-term problem for anything that's asexual. Works like this.



In a small population, the class of organisms that has the fewest mutations is eventually lost by drift. Okay? So you should think of this starting off with a perfectly clean population of let's say bacteria. It's a small one, there are only ten or twenty of them. None of them have any mutations. Then the first mutation arises, and eventually it drifts through the population and it is fixed. That will eventually happen. At that point all the organisms in the small population have one mutation.



Because they all have one, they can't get rid of it. The process happens again. Then they have two, and so forth. So that leads to an inexorable increase in the number of mutations in the class of organisms that has the fewest. It goes--the fewest goes from zero to one to two to three, and so forth. And the kinds of organisms that are afflicted by this would be mitochondria and chloroplast in the germ line, and ancient asexuals like bdelloid rotifers.



What's going on basically is that this correlation between reproductive success and trait or genetic state gets wiped out by the Law of Small Numbers. As you decrease the size of the population, it becomes less- natural selection becomes less and less powerful. You just get more noise, simply due to sampling issues; you just have a smaller number of organisms, so the tightness of the correlation goes away, it gets noisy.



So the smaller the population, the more important random events are. When it's very small, natural selection has very little opportunity to operate, and the reason it loses its force is that the correlation of trait variation with reproductive success is lost in the noise of a small number of arbitrary events.



So that's what's going to go on when say you start off an oocyte with two or three mitochondria; that's a very small number of mitochondria to go into an oocyte, and that's a genetic bottleneck through which mitochondria will go in every generation. There might be 10,000 of them in your liver cells, but if they're a small number in oocytes, then they are going to experience drift.



So you can think of this as stochasticity driving a wheel around, and there is a lever here that allows it to go forward but won't allow it to go back. The capital letters are beneficial genes, and the small letters are mutations, and Muller's ratchet will take this population and at first one of these genes will get replaced, through drift, by a deleterious mutation; then two; then three; then four; then five; and so forth. And if you plot here, from few at the top to many on the bottom, the number of deleterious mutations that are carried by the least loaded genotype--that is, the type in the population that has the fewest deleterious mutations--it's increasing, and fitness is going down.



This won't happen in a sexual population, and it won't happen in an infinite asexual population. The infinite asexual population is big enough always to have some individuals in it that don't have any mutation, and they will keep taking over. But in a finite asexual population, Muller's ratchet operates.



So it's important in organelle DNA, and this problem of Muller's ratchet in organelle DNA could be solved, for example, if mitochondria had sex. There has been a controversy over whether mitochondria have sex, and if you would like to read a paper that was written for this course on that issue, it's up on the website--it's called Example Paper--and it reviews the status of that issue about two years ago.



In mammals, mutations in organelle DNA may be solved with gamete selection through oocytic atresia. One of the reasons why female mammals may make 7,000,000 oocytes, when they're embryos, and then kill most of them before they start menstruating, is that they are getting rid of mutations that may have built up in the mitochondria.



What about the ancient asexuals, those bdelloid rotifers? Well they have really two possibilities. One is that they could try and arrange their physiology so that they could make the effects of any mutation more serious. And that has been suggested as a hypothesis, and I find it implausible; but it's a hypothesis which is out there.



If you can make any mutation really serious, so that it kills anything that it occurs in, it has no chance to accumulate. It's only the deleterious but not fatal mutations that can accumulate. So that's a logical possibility, but biologically I find it implausible. Or they could always maintain a very large population, so that drift is not a problem. And most of the things that are ancient asexuals do have at least large populations; not infinite but certainly large.



So here's a bdelloid rotifer, and it's managed to escape these problems. Nobody has ever seen a male bdelloid rotifer. You could go outside OML and take some moss off the side of the building and put it into a cover slip, and some bdelloid rotifers would swim out of it. They're all over the planet. Even though it's avoided the problems with mutations, we don't know how it's dealt with pathogens and parasites. Okay? And that's this next issue.



Parasites are the principle way that the idea of co-evolution is realized in the context of the evolution of sex. What happened to the Red Queen, or what happened to Alice when she met the Red Queen in Lewis Carroll's book Through the Looking Glass? Did any of you run into that? Alice sits on a chess board and she is--this is kind of in a dream--and she's trying to march down the eight squares of the chess board so that she can be promoted to a queen. She's a pawn in the chess game, and she's trying and trying to get there, and the Red Queen comes up to here and says, "Alice, in this game you have to run as fast as you possibly can, only to stay in place."



So it's called the Red Queen Hypothesis, and the idea is that in evolution organisms are evolving as fast as they can, but they're in fact not increasing their fitness, and they are not decreasing their long-term extinction probability because the parasites and pathogens in their environment are coevolving with them and keeping up with them. So it's called the Red Queen, basically to communicate the idea that if you are in a co-evolutionary arms race, then you may have to run as fast as you possibly can, just to stay in the same place.



So what it requires is genetic variation for resistance in the host; genetic variation for virulence in the pathogen. We can see that in Daphnia and its parasites, and in crop plants and their pathogens. So the assumptions appear to be fulfilled in some well studied systems, and you can see some of the data here. Okay?



So this is a case--this is a complex table. I'd like you to be able to interpret things like this. Basically what's gone on here is that ten clones of Daphnia--or is it nine?--nine clones of Daphnia have been isolated from a lake, and out of each of those clones a strain of a parasite has been isolated. This parasite is Pasteuria ramosa, and it infects the body cavity of Daphnia and castrates it. Okay? Often parasites castrate their hosts.



The numbers are the percentage infected. Okay? If you look at that you can see, for example, that this strain of Pasteuria is really good at infecting the host that it came out of, and really lousy at infecting this other clone of Daphnia here; does pretty well in E and G; and very, very poorly in B, C, F and H. So one way to look at it is to ask, "Where do the parasites do well?" And the answer is, only in some of the clones.



Now if you ask, "How about the Daphnia, how are they doing against the parasites?" Well you can just go down a column and you can see that this Type D here is actually pretty resistant to almost everything out there, and at the worst it gets hit by this parasite that came out of clone G, over here. So from these data you can conclude that there is genetic variation for resistance and there is genetic variation for virulence, in a natural population.



The parasites are selecting for host resistance. The hosts are selecting for parasite virulence, but the parasites have to keep hopping around, onto different hosts. The parasite selection is happening on a time scale of days, and prevalence of a particular parasite decreases as resistant host types increase in frequency. So that's just what you need to maintain sex. Okay? So that one looks pretty plausible.



There's another example from nature that's pretty well studied, and that's worms living in snails and ducks in a beautiful lake on the South Island of New Zealand, and the people who get to go study this stuff go to one of the most beautiful parts of the world, where they then put on wet suits and dive into freezing cold water. [Laughs] Okay? The behavior of scientists is difficult to explain.



So this is the lifecycle of the worm. The adult worms are in the duck. They make eggs. The snails pick up the eggs. The worms reproduce in the snail's body. Then they are excreted as cysts. The ducks eat the cysts, and the life cycle goes around like this. Okay? So anytime this loop can be completed, the worms can stay adapted to the snails and to the ducks. If this is broken at any point, then the worms are no longer adapted to the snails, or to the ducks.



This is the kind of situation in this lake in New Zealand. The ducks are in shallow water, and the worms come out of the ducks and infect snails. They only manage to close the loop in shallow water, because the ducks don't dive very deep to eat the snails. The worms that are coming out of the snails and going into deep water are from a source, and they're going into a sink, and they become maladapted to the snails; they can't keep up with the evolution that's going on, in the snails down here, because just about everybody that's getting into the snails down here, in fact, is adapted to the ones in shallow water.



So up here there's more snail sex, and down here there's less snail sex. And that's a very short distance. We're only talking about maybe twenty or thirty meters apart, for these populations. The only difference is the depth of the water, and whether that loop is connected or not. And where the loop is broken, where the parasite cannot complete its sexual life cycle, it loses the arms race with the snails. The snails don't need sex. Asex takes over and spreads through the population.



So asex hardly ever has an exactly twofold advantage. It's a bit more difficult usually in animals, and sometimes it's easier in plants than 2:1. There are cyclical parthenogens--Daphnia, some aphids, some beetles, have a series of asexual generations, followed by one sexual generation, and the analysis of these guys has led us to the conclusion that you don't need very much sex, but you do need a little. You can have sex about once every ten to a hundred generations, and it is almost as effective as having it every generation.



And in mammals and birds, there are no costs of sex, because the asexual alternative is impossible, and that is because early development requires genes from each parent to activate in complementary fashion. So when you were a very, very small embryo, consisting of a few cells, you had to have some genes from your father turn on, and then some genes from your mother, and then some genes from your father, and then some genes from your mother, in sequential fashion, or development would not occur.



That pretty much means that asexuality becomes impossible. Asexuality would only work if that whole developmental sequence could be carried through only by genes from the mother. And apparently there has been a process, an evolutionary arms race, probably involving conflict resolution, that has led to the kind of development that birds and mammals have.



There's an irony in this. We now have so many advantages of sex that we have a hard time explaining asex. How did those bdelloid rotifers survive? We can easily understand why asexuality would repeatedly originate and spread. It can spread like gangbusters. It has low cost short-term; big cost long-term. The long-term cost basically is pathogens and parasites, even if it can arrange a solution to the mutations that drive Muller's ratchet. Okay? So if you look at the Tree of Life, what we see is that the asexual types are up on the twigs and they have sexual ancestors.



And most of the asexual types are not too old; they're usually on the order of somewhere between 50,000 years and 10,000,000 years, and there are very few of them that are older than that. It appears that these forces catch up with them in the long-term, and drive them to extinction more rapidly and more pervasively than they can drive sexual types to extinction.



So we have good individual selection explanations for recombination. You don't have to invoke group selection or species selection. It has a lot of explanations. The ones that seem to be pretty general are repair -- mutations - and parasites. Those are certainly experimentally substantiated. We do not understand how ancient asexuals have survived; that's an open issue. And sex has had some very important macroevolutionary consequences.



Probably the most striking is the very existence of species. We would not have things in nature that we called species if there were not sex. Instead we would have clones that just kept fragmenting and kept filling in morphospace fairly continuously. What sex does is it integrates populations and causes the co-adaptation of their genomes, so that we get breaks separating the things that we call species. They are things that hang together. The other is this phylogenetic distribution of asex. It's up on the twigs, it's not down on the main stems of the Tree of Life. Next time we're going to discuss genetic conflict. It's something that happens, and it happens much more easily in sexual than in asexual species.



[end of transcript]



 

Genomic conflict arises when the interests of various genomic elements, such as chromosomes and cytoplasmic organelles, are not aligned. These conflicts arise in two situations: either when one unit is contained within another, as a mitochondrion is contained within a cell, or when inheritance is asymmetrical. Genomic conflict can thus occur within a cell, within an organism, or between two organisms, such as a mother and developing fetus. There have been several steps taken to avoid these conflicts in sexual species, including the fairness of meiosis and the uniparental inheritance of cytoplasmic genomes.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 9

Transcript



February 4, 2009



Professor Stephen Stearns: Okay, today we're going to talk about evolutionary conflicts, and this is an area of evolutionary biology that contacts other disciplines, including the Humanities, in interesting ways. I was reading Nature this morning and there was a review of an off-Broadway production about the life of Robert Trivers, whose picture you're going to see here, and it was about Robert Trivers as a disturbed young genius at Harvard coming up with ideas of conflicts of interest and whatnot, and the actor on the stage was going on about how tormented the young Trivers was, and he was smoking pot and all of this stuff, and having his great ideas, and upsetting the faculty at Harvard, and finally giving up in disgust and going to Santa Cruz and meeting Huey Newton and the Black Panthers and all of that stuff. Okay? And there was a guy in the back of the theater who was chuckling and came up and congratulated the actor afterwards, and he said, "You got it just right." And it was Bob Trivers, who was watching. Bob's a professor at Harv--at Rutgers now.



So we're going to be talking about interesting stuff today. And I want you to be aware that the first part of it is well-founded, well-supported, experimental science, where the conclusions that I'll present to you are quite reliable. And at the end of it, I am going to go into some speculative stuff, where the conclusions aren't so reliable, but it's very interesting. And I want to say that up front so that--and I'll give you a signal when I transit from reliable stuff to speculative stuff, because I don't want you thinking that the speculative stuff is written in stone.



So let's begin by looking at these plant flowers. These are pPantago flowers. Plantago is something that you may very well have dug out of your lawn. It is a rosette plant. It is a common plant around the world, and it is gynodioecious, which means that it has two kinds of flowers. It's got flowers that have both male and female parts, and it's got flowers that just have the female parts and greatly reduced, or almost absent, male parts, male sterile parts. And evolutionary sex ratio theory tells us, in fact, that from the point of view of the nuclear genes, it's best to have a 50:50 sex ratio and to be investing 50% in male and female function; and we will come to that soon.



However, in this organism evidently, in some of them, this 50:50 sex ratio has been subverted, and all they do is reproduce as females. Now it turns out that the genes that control this morphological switch are in the cell organelles; they're not in the nuclear genome. The genes that are sitting in the organelles in the cell, be they mitochondria or chloroplasts, can only get into the next generation through female function, through the eggs. They are not transmitted through pollen. It is in their interests to take the organism that they're sitting in and turn it into a pure female. And you can see that dramatically in the external morphology of the plant.



This same process goes on in insects and in crustaceans, when they are infected by a cytoplasmic bacterium called Wolbachia. It is in Wolbachia's interests only to occur in females, because they can only get into the next generation in eggs; they can't get into the next generation in sperm. And Wolbachia will feminize the organisms that it's in, and in some cases Wolbachia will kill the males, so that the male offspring don't develop. So these are cases where the conflict of interest is arising because there's selection going on at two different levels; on the whole organism, and then within the cell, on the cytoplasmic organelles.



So if we look into our own genome--and I'm going to spend the last twenty minutes of this lecture looking into our own genome--we see a very interesting thing. If there's potential, through either hierarchical selection or asymmetry of information transmission, to generate evolutionary conflict, then we see that we're not even in principle the consistent wholes that you might think we are. And a very famous guy said that, "Perhaps this is some comfort when we face agonizing decisions, when we cannot make sense of the decisions we do make, and when the bitterness of a civil war seems to be breaking out in our inmost heart."



And that was Bill Hamilton, the guy that came up with kin selection, and wrote a lot on evolutionary conflict. And it's fairly poetic. And Bill actually liked haiku a lot. He particularly liked Basho's famous Narrow Road to the Deep North, which is--Basho was one of the greatest Japanese haiku writers, and was a favorite of Bill's.



So there are interesting implications of what we're talking about today, and the outline basically is going to be how you can generate genomic conflict out of hierarchical selection. I'm going to make a strong point that the opportunities for conflict are much greater in sexual than in asexual species. Then I'll mention that the uniparental transmission of cytoplasmic genomes is probably a method of conflict resolution. Then I'll go on to talk about genomic imprinting and parent-offspring conflict in mammals. And then that outline there represents what is well-established and reliable. When I go off this outline, at the end, I'm going into the speculation.



So conflict can arise in two situations. One is the Russian doll situation, the babushka situation; multilevel hierarchical selection. That is when one selection process is contained inside another selection process; and here you should think of things like meiotic drive and cancer.



The other situation is where the transmission is asymmetrical, so that the different genetic elements in the system do not all follow the same transmission pathways. The cytoplasmic organelles are the classic example. They can only go through the female line, they can't go through the male line. The nuclear genes are going equally through both male and female inheritance. So there's a large and striking difference in the way the cytoplasmic organelles are inherited.



So when we think about two-level selection, there are really two things that can be going on. For example, here we have two genetic entities contained inside a larger thing. Okay? If A has a replication advantage, at the lower level, then it can just build up more copies of itself, and then when this larger thing divides and reproduces, it will end up in more copies, because at this stage it was reproducing faster.



Think petite mutation in yeast. A petite mutation in yeast is a mitochondrial mutation, and basically what the petite mutation does is it cuts out a chunk of the DNA in the mitochondrial genome, so that the mitochondrial genome can be replicated faster. Now, of course, if you cut out a bunch of the mitochondrial genome, the mitochondria aren't doing their job of being a good energy factory so well, for that cell that they're living in. So they're gaining an individual advantage from mitochondria, but they're damaging the interests of the cell that contains them. And what happens is that the ones that cut out the DNA, that can replicate faster, do build up a replication advantage at the lower level.



The other possibility in two-level selection is that there's a segregation advantage. There are just as many copies made of each type, at the lower level, but in the process of then forming say the gametes--so in any replication process, either mitotic or meiotic, if there's a segregation advantage, one of them is going to get into more copies. So it takes the same number, and then just in the process of making the new cells it gains an advantage. And think here meiotic drive. Okay, so that's the paradigmatic example for segregation advantage.



So in the petite mutation in yeast, what's going on basically is that there's a deletion in the mitochondrial genome. That allows the shorter genome to be replicated faster. It builds up a big population in the cell. However, there's a disadvantage at the higher level, and that is defective metabolism. The result is that the cell lineage goes extinct. And so people who work on yeast in the lab--if you just take a big population of yeast and you played it out in generation after generation, these petite mutations keep popping up, and they spread, and then they go extinct. They have a lower level replication advantage, but they have a high cost for the cells that contain them, and they disappear. It's almost exactly analogous to cancer.



In an asexual lineage, the only kind of conflict that is in principle possible is one selection process contained inside another one, and the conflict would occur if the lower level response differs from the higher level response; so if what's good at the lower level is bad at the higher level. Petite mutation is a good example.



There's no horizontal transmission there, because there's no sexual reproduction going on. So two independent lineages are not coming into contact with each other and mixing; they're staying separate through generations. And so there isn't any way for the lower level response to escape the fate of the upper level response. So if there's a significant conflict, a significant cost, the lineages will die out. So this is something that actually can drive asexual extinction.



In a sexual lineage, sex is creating genetic variation within the nuclear genome. It has the potential to create genetic variation in cytoplasmic genomes, and it creates opportunities for non-chromosomal genetic elements to change hosts; particularly interestingly in bacteria it does this. So some kinds of mechanisms, that are going on during sex, formally resemble pathogen transmission; the transmission of--when you cough up a virus and it gets into your roommate, basically a genome is moving horizontally from your body into another body, and reproducing there, and during sex there are opportunities for this kind of thing to go on, from one bacterium to another, and certainly in organisms like us, from one organism to another.



So one cost of sex might be the potential it creates for inter-genomic conflict. I'm not talking here directly about sexually transmitted diseases like gonorrhea or syphilis. I'm talking about the possibility that genetic elements infect the genomes of other cells.



So, for example, there could be a conflict between bacterial plasmids and chromosomes. A little background on bacterial genetics. Bacteria usually contain plasmids, and these things are small circular genetic elements and they live in the bacterial cytoplasm. So you can think of them as genetic parasites. The rest of the bacterial genome is a large single circular chromosome which is attached to the cell wall of the bacterium. So think of the bacterium as a balloon that has a circular rubber band attached to the cell wall, but then out floating in the balloon are these much smaller plasmids that contain DNA and do particular things.



The plasmids often are the elements in the bacterium that have genes for antibiotic resistance, and they can be advantageous when antibiotics are present. There are other plasmids that will addict their host cells, the bacterial cells, to their presence by making a poison antidote system. Okay? So basically what they're doing is that they're protecting their own cells and they are producing chemicals that destroy cells that don't contain the plasmids.



And this is a general principle. If you make a long distance poison and a short distance antidote, you protect the environment that you're in and you destroy the competition. So any bacterial cell that doesn't inherit the antidote, via a plasmid, but gets the poison, will die. So that changes selection dynamics, at a higher level, and this plasmid will spread through the population.



Very similar to that, in some sense, is segregation distortion. There is a gene that was first found in mice and--this is important--it's just an arbitrary accident of developmental biology that this segregation distorter happens to also result in mice with short tails. Okay? That's just an accident of pleiotropy. This gene has effects on both segregation distortion and on tail length, in mice. So you can think of the fact that it's affecting the tail as just a marker; it's just kind of like having a reporter gene in there. And we'll simplify the situation and just consider two alleles. There's a t and a normal allele that we call +. Okay, so these are the two versions of this gene that are sitting at the same place in the chromosome. If you have tt homozygotes, they're lethal or sterile. So if that were the only thing that were going on, you'd never see this thing; it would die out real quick.



But if you have a mouse that is heterozygous with t and +, they produce--they're fine, they live just fine--and they produce 90 to 100% t-bearing sperm. This is again done with a long distance poison and a short distance antidote system. So sitting there in the testes of the mouse is a cell that is making sperm, and some of them have the t and some of them don't, and the sperm that have the t in them are making poison, which is going over and killing the ones that don't have the t. They're sitting spatially right next to them in the testes, and the sperm that have the t are also making an antidote, but it's only effective inside their own sperm. So basically what's going on is that t's just wiping out the competition, inside the testes, and that ends up producing 90 to 100% t-bearing sperm.



So you have hierarchical selection at the level of the gamete. You have got selection for t and against t, up at the level of the diploid individuals, because up there the tt homozygotes are lethal or sterile. So a 50:50 sex ratio--ignore that, this is irrelevant right here; this is for, this sentence snuck in here for a different kind of gene action. So this sentence is--and I regret that, I should've edited that out.



If the tt homozygotes didn't die, but they suffered a sufficiently small, sub-lethal fitness reduction--so if this part here were not true--then t would spread, and eventually if t spreads all the way through the population, everybody's got the antidote, and you don't have any segregation distortion anymore, and everything goes back to normal. If that is the case, once t takes over the population, there's no more segregation distortion.



This introduces the interesting possibility that most species may have had a history of segregation distortion and we just don't notice it anymore, because they've gone to fixation. In fact, we don't have any easy method of detecting that. We may see the traces of that, written in the history of things like the fairness of meiosis, but we can't go out right now and easily find genetic or biochemical evidence that we have fossil segregation distorters sitting in our own genome. It seems likely that we do, but we don't know.



Now what about conflicts between the nucleus and the cytoplasm? Well any cytoplasmic genome, that's replicating faster, gets a segregation advantage, because there isn't any meiotic mechanism that assures fair segregation of organelles. The chromosomes are controlled by the spindle apparatus. They line up at the plate, at the middle of the cell. They make two copies. The spindle grabs one copy and pulls it one way, and the other copy and pulls it the other. Okay? So that's really fair, that's exactly 50:50.



The organelles are out there floating around. They're not attached to a spindle when the cell divides, and so basically if they can just make more copies of themselves, they'll have a better chance of getting into the dividing cells.



If you had biparental inheritance of cytoplasmic genomes, that would mean that in the same cytoplasm you would have genetically different, unrelated mitochondria; genetically different, unrelated chloroplasts. And the consequence of that would be conflict, and that would be expressed as an organelle cancer. If you only get the cytoplasmic genome from one parent, then they'll very likely all be the same genotype--any kind of process like this going on in the past would have assured that there would only be one left standing, in that parent--and therefore they're not in conflict with each other.



So, in fact, you all only contain mitochondria from your mothers. It's extremely rare that a human will ever have a mitochondrion from a father. It does happen, but it's a one in a billion chance. Okay?



So those are some of the well established cell level scenarios in which conflict plays out. And before I go into the reproductive problems in humans that result from conflict, I'd just like to emphasize that this vision of evolution doesn't sound like the beautifully adapted world where all is for the best, in the best of all possible worlds. This is a vision of evolution in which there is continual conflict, and in some cases it's never resolved, which means that in some cases both sides are paying a continual price. So that's quite a different way of looking at the world. And if you're trying to derive simplistic take-home points, from the evolutionary view of the human condition, one of them would be, as you'll see in a few minutes, that there are probably long-term conflicts that are never resolved.



So reproductive problems. In mammals there are conflicts between mother and fetus over how much the mother should invest in the fetus. The symptoms of that are pre-eclampsia and diabetes. There are conflicts between mother and father over maternal provisioning, and those are related to genetic imprinting of growth genes, and there are disturbances and a tug-of-war balance produced by evolutionary conflict in genes that are expressed in the infant brain, and those are thought to deal with mental illness. This is where the line is between well-established science and speculation.



So the arenas in which these things play out are in the placenta and uterus, and in the developing brain. And this is the sequence of ideas; so I'll give you a little intellectual history. 1961, '62, Bill Hamilton has the idea of kin selection, the idea that we can- a gene can increase its fitness, either by its actions on my own body, or by influencing the actions that I take to improve the reproductive success of relatives in which that gene also probably exists. Then Bob Trivers developed Bill's idea into parent-offspring conflict. And the idea of parent-offspring conflict--which I'll state a couple of times to make clear--is this.



A mother is 50% related to all of her offspring. She is interested in making sure that each of them has an equal chance therefore to have grandchildren. Now switch your point of view to one of the offspring. It's 100% related to itself; it's 50% related to a full sib; and it's only 25% related to a half-sib. So from the point of view of a gene which is sitting in our focal offspring, it wants to titrate its mother's investment away from its potential future siblings and into itself, until the probability of grandchildren, through itself, exactly matches the probability of grandchildren through the others multiplied by degree of relationship. Okay? It will have a full-sib if the species is monogamous, and it has a probability of half-sibs if the species is polygamous; if the mother mates with multiple males. So that was Bob's insight.



Bill got the Crawford Prize, which is the Nobel Prize in Evolutionary Biology, for kin selection, and Bob got it for parent-offspring conflict. So those are prizes that are worth oh six or seven-hundred-thousand dollars, and like Nobel Prizes, they are awarded in Sweden, in Stockholm. And so these were seen as big, important ideas.



Now David Haig then picked up on Bob's idea, and he said, "Well, there's not only conflict between parent and offspring." And that conflict, by the way, is also realized through imprinted genes in pregnancy. There is conflict between the mother and the father over how much the mother should give to the baby, and the baby take from the mother.



So if the father can put into the baby a gene that then extracts more from that mother than the mother wants to give, the father can gain, to a certain point, an advantage. This isn't an absolute thing, it's just saying that there is a range of investment where it is not advantageous for the mother to give more to the baby, but it is advantageous for the father to get the mother to give more to his baby. Okay? And this is mediated by genomic imprinting.



The final step in this little bit of intellectual history is Bernie Crespi and Chris Badcock, who came up with the idea that this conflict that David Haig identified, which is going on during pregnancy and is probably mediated mostly by genes that are having interaction in the fetus and in the placenta, extends into early life during the period of suckling, before the child is weaned, and the conflict is then expressed in genes that are in the brain of the infant, and when their tug of war, which is in evolutionary equilibrium, is disrupted, Crespi and Badcock think that you get mental disease.



So this is Bill. This is taken on the Amazon. Bill died in the year 2000, after trying to find the source of AIDS in the Congo. He had gone to the North Kivu to see whether or not he could find chimpanzees whose DNA might match DNA in polio vaccine from the late 1950s. There was a hypothesis at that time that that's how HIV got into humans, through polio vaccine. It turned out to be wrong, and Bill died just after that trip.



This is Bob Trivers, recently. He's a prof now at Rutgers, and Bob had the parent-offspring conflict hypothesis, as a grad student at Harvard in 1969, '70, '71; about there. This is David Haig, currently a professor at Harvard, and the guy who came up with the observation that there's a very intriguing connection between the imprinting, the differential imprinting of genes in the male and the female germ lines, and the control of growth by the embryo. And this is Bernie Crespi and Chris Badcock. So Bernie's at Simon Fraser in Vancouver, British Columbia, and Chris is in London, at the London School of Economics. So these are the guys who had these ideas about evolutionary conflict, expressed in humans.



There was a news item on the local television station the other night that Jacob Lykke's research on preeclampsia had just been published, and it was sort of playing up the idea that research from Yale Medical School reveals important pregnancy complication consequences; women who have preeclampsia have worse health later in life. That basically is a continuation of this idea. The OB/GYN Department at Yale Medical School has picked up on this stuff.



Okay, so let's run through the logic. The conflict between mother and fetus over maternal provisioning is basically this: the fetus is selected to extract more from the mother than the mother is selected provide. It's 100% related to itself. She's 50% related to each of her offspring. It wants to take more from her. She wants to hold some back, so she can give the same amount to future offspring. The way that it will do this is by using tissue in the placenta to secrete hormones into the mother to manipulate her metabolism.



It also does it, by the way, morphologically. It is fetal tissue in the placenta that invades maternal tissue, aggressively, and establishes tighter and tighter connections with the maternal blood circulation. So if you look at the origin of the cells in the placenta, there's a morphological story of conflict written there as well.



So the symptoms experienced by the mother are high maternal blood pressure and pregnancy-related diabetes, and this will happen particularly when this gets a bit out of balance. So if you're a baby, sitting there in the womb, and you want to get more out of mommy, you can do two things. You can pump up her blood pressure so it'll force more nutrient through the placental barrier, and you can play with her metabolism so there's more sugar in her blood. Too much of that and the mother gets pretty sick.



This is the arena in which it occurs. This is the fetal portion of the placenta here; you can see the invasive blood vessels going in, over here. This is the maternal portion out here, and this is where the exchange of nutrients is mediated.



So the evolutionary logic behind this is that--if we now look at the mother-father conflict--the father isn't going to be related to the mother's later offspring, if they have other fathers. And, by the way, I'm now going to make a series of statements that sound like humans are engaged in absolutely outrageous moral practices.



None of this logic necessarily is going on in current evolution, in our current human population, because you can demonstrate these effects in mice, and we shared ancestors with mice about sixty million years ago. Okay? So a lot of the machinery that's being detected in mice and in sheep and in humans, that is shared, could very well have had to do with the polygamy, or lack of monogamy, in ancestral mammals a long time ago. Or it could still be going on.



Now there is an asymmetry in the male and female reproductive possibilities. The father's reproductive success depends on his successful matings. The mother's reproductive success depends on the number of offspring she personally can bear. And if you state that brutally, he can have several children and other females, while she's dealing with this one.



So here is a Mormon polygamist. He has two wives. This brother is 50% related to this sister, and 25% related to this brother. Okay? So bear that scenario in mind. That is the sort of thing which is driving the selection pattern. Rare today in humans; possibly much commoner in the past.



What does this have to do with imprinting, and what is imprinting anyway? Imprinting is a process of methylating genes, and if you imprint a gene, you turn it off; it will not be transcribed if it's methylated. Imprinting is used in a number of contexts. It's an epigenetic mechanism that's used in development to control cell fate.



But the kind of imprinting that we're talking about today is a special kind. It's differential imprinting by sex, and it's not happening during the development of the body in order to decide whether a cell becomes a liver cell or a brain cell, it's happening in the germ line of the parents, just before the gametes are produced. And the point is that the father is imprinting certain sets of genes and turning them off, and the mother is imprinting other sets of genes and turning them off. Okay?



These genes that are imprinted in the germ line are not expressed in the fetus, and they are then reprogrammed in the germ line of the adult. The adult could be either male or female. Right? So when it makes its gametes, in the next generation, it doesn't make them with programming the imprinting pattern it had when it was a baby, it makes them with the imprinting pattern that is appropriate to its sex.



What's going on is this: The father is turning off genes that down-regulate growth in the embryo. The mother is turning off genes that up-regulate growth, and so basically--it's kind of double negative, because the father's turning off stuff that acts in the mother's interests, and the mother's turning off stuff that acts in the father's interests. But the upshot of that is that the father is trying to program the embryo to extract more than the mother is prepared to give, and the mother is resisting.



You can only see this going on when you disturb the equilibrium. You can disturb the equilibrium in a number of ways. You can do it by genetically transforming mice, and the gene that you choose to disturb the equilibrium is the gene that does the imprinting. Okay? So you mutate that gene, or you delete it, and then you observe the outcome. And the effect is roughly plus or minus 10% in birth weight.



So if the father's genes are--if the mother's genes are not doing their job, so that only the father's interests are expressed, the embryo is about 10% heavier; and if it's the other way around, the embryo is about 10% lighter. This scenario is also supported by the fact that if you look at all of the genes in the body, there are only about 100 or 200 that are imprinted. There are very few that are imprinted differently in the mother and in the father, and the ones that are imprinted differently in the mother and the father mostly have to do with the control of fetal growth.



So it's a very special set of genes, and they are clearly associated with the specific function of fetal growth, rather with the millions of other things that genes do in the body. So up to here, you can do nice manipulation experiments on mice, and these have also been done in things like sheep, and the scenario stands.



Now, going into speculation. The primary site is the placenta, where there are small deviations that can benefit child or mother. Large deviations are costly to both. So the normal situation might be that there would be a small deviation. You only get a big deviation and disease when there's a real disruption of the imprinting patterns and they get out of balance; so that if you're thinking of a tug of war, one side falls over. Okay?



Where are the rest of these genes? They're in the brain. These are the sex differentially imprinted genes, the ones that are imprinted differently in mother and father, and they're not controlling fetal growth or being expressed in the placenta, but they are being expressed in the brain.



And this is now Crespi and Badcock's idea. A deviation toward paternal gene expression should result in a relatively selfish offspring. So it should be trying to take more from the mother, and it should be doing it now through infant behavior rather than through fetal physiology. And a deviation towards maternal gene expression should result in an easy offspring that would be letting the mother relax and store up nutrition for the next baby.



So we can't do experiments on humans to--like we can say with knockout genes in mice. So what Crespi and Badcock have done is they've looked at neurogenomic syndromes, single gene effects, and idiopathic psychiatric conditions, to see what happens when this tug of war in the brain is disturbed.



Well probably the most revealing early observation--this was actually picked up by David Haig, before Bernie got into this--is that there are imprinted genes on chromosome 15, that are expressed in the brain, and if the maternal copy is deleted or modified, you get one syndrome, and if the paternal copy of this same gene is deleted, you get another syndrome.



So Angelman syndrome is that the maternal copy is deleted. The paternal copy is only imprinted in the brain; it's not imprinted in other parts of the body, it's very specifically imprinted in this tissue. And Angelman children are happy, retarded and uncoordinated. The same gene, but with paternal copy deleted, maternal copy imprinted, you get, after the age of two, you get uncontrolled eating, hypogonadism, delayed puberty, and a completely different syndrome. Okay?



So the Angleman types, with father's interests over-expressed, have prolonged suckling, frequent crying, hyperactive, sleepless; they're difficult children and they have high rates of autism. And the Prader-Willi children, with maternal interest over-expressed, don't feed very well, they cry weakly, they're inactive or sleepy, and they have high rates of psychosis; some kinds of psychosis are called schizophrenia.



So what Crespi and Badcock proposed is that if there's an imbalance during fetal development, in the brain, towards paternally expressed imprinted genes, you get higher birth weight, a larger brain, faster growth, a cost to the mother. The costs to the mother are coming from selfish, egocentric cognition and behavior, and both mother and child are bearing costs from any of the negative aspects of autistic spectrum. Okay?



If the mother's interests are over-expressed, then during fetal development you get a smaller birth weight; you get a smaller brain, less lateralized brain; slower growth. The benefits to the mother is that the child is easier to take care of. There's a cost to the offspring, it has schizophrenic behavior. And there's also eventually a cost to the mother, from the schizophrenic behavior.



So the people who have featured here--this is just an autistic child sleeping on his hands. That's Sylvia Plath, the poet who committed suicide. And if we look at the correlative evidence from idiopathic schizophrenia and idiopathic autism--so I think you know who those guys are--what you see is that associated with schizophrenia of unknown cause--that's what idiopathic means--is low birth weight; slow growth; small head/brain size; better verbal; dyslexia; some overlap in the genes with bipolar disorder; major depression.



And if you look at autism, you see that they have higher average birth weight; so not always higher, but not lower. They have faster body growth. They tend to have large heads. They are called hyperlexic. They have better visual, spatial and verbal skills, and you can get an idiot savant syndrome out of that.



So there is correlative evidence. This is not experimental, but it is possible to go out there in the literature and to pull together a lot of studies and say, "Hey, it looks like there are correlations with what you might expect if this was an over-expression of maternal interest and this was an over-expression of paternal interest in the infant brain."



Now if this connection between evolutionary conflicts of interests and mental disease is ever actually established, it's going to be one of the most remarkable connections that I know of. It was completely unexpected. Nobody ever thought that an alternative explanation for autism and schizophrenia would ever come out of kin selection and parent-offspring conflict. Okay? Certainly that was completely unsuspected in the '60s, '70s, '80s and '90s.



So I'd now like to pause and just remind you that everything that I've told you about a potential connection between evolutionary conflicts of interest and mental disease is speculative. It is actually at the moment an object of rather intense research. But the annals of research journals are littered with the corpses of beautiful ideas that were killed by facts, and that could very well happen to this one. We have to be patient and just see what happens. But I hope that I've been able to communicate to you that there is a role in science for bold speculation, and that it actually makes the whole process extremely interesting.



Now I'd like to do something that occurred to me after I had lunch with Bill Feldman yesterday. Bill's taking this course because he's a political scientist, and he's interested in what evolution has to say about politics. So I want to give you some take-home messages about conflict resolution that come out of the study of genomic conflict.



If you want to get rid of a conflict, make the interest of the competing elements symmetric. You can do this in a host pathogen relationship by shifting the transmission from horizontal to vertical. That will reduce their virulence. Because, if you think about it, then the pathogen can only get into the next generation if its host survives. If it's a vertically transmitted parasite, that means it's transmitted from parent to offspring. So the parent has to survive, to have a baby, so that the pathogen can make it. So it's not in the pathogen's interests to kill the parent. A horizontally transmitted pathogen, on the other hand, can have actually quite a high level of virulence; and that is where all the major diseases are, they're all horizontally transmitted pathogens.



And if you think about things like Wolbachia--remember, I was telling you about this bacteria that feminizes its hosts, so that it would always be occurring in the body of a female. Well there's some crustacea that have figured out how to solve this problem. They take the Wolbachia and they chop out its sex determining gene, and they implant the Wolbachia sex determining gene on one of their chromosomes, et voilà, there is no conflict anymore because now the whole business is vertically transmitted.



So they just took the offending element, that one offending element out of the bacterium, and they stuck it into their nuclear genome, and they created a new sex chromosome for the crustacean. So they also got--they made the interest symmetric. Both genetic elements then had the same vertical transmission route.



Another way that you can resolve conflict is this. You can suppress the meiotic drive. So you can punish the offenders. And the evidence for that basically--that there's been a history of suppression--is the fairness of meiosis. You can also homogenize the reproductive success of competing elements within a group, at the human level. This can be done with monogamy. Anything that will make individual success depends on group success.



So I'm going to give you a couple of taglines to remember this, a couple of mnemonics. A rising tide lifts all boats, and we're all in the same boat. So if you're a gene, you should think that anything that you can do to improve the reproductive success of the organism that you're sitting in, is probably the only way you'll improve your own, and the fact that it's improving everybody else's reproductive success, in that same genome, is actually irrelevant to you. You're not competing with them; in fact, you're all cooperating, because if you're all in the same boat, and you're all pulling together, that's the only way to get into the next generation.



And, of course, there is this anecdote--this isn't--we don't actually know if this is a direct quote or not. But it is said that as the Declaration of Independence was signed on July 4th in Philadelphia in 1776, Benjamin Franklin turned to the people who were signing it and said, "Gentleman, we must indeed all hang together or assuredly we shall all hang separately." So these are just mnemonics. These are ways of remembering the principle that the way to suppress conflict is to generate a situation in which everyone is dependent upon partners for success.



So the take-home for the lecture basically is this. You should think of organisms as a hierarchy of replication levels, and natural selection can occur simultaneously at all of the levels in the organism. This is especially important with cytoplasmic organelles and with meiotic drive.



Replicating units that only occur in a few copies, and whose replication and segregation are strictly controlled--things like cell nuclei and chromosomal genes--do not easily cause genomic conflict. But if those units occur in many copies, and if their replication and segregation is not strictly controlled--those are things like cytoplasmic genetic elements--they more easily cause genomic conflict. Conflict is much more easily evolved and experienced in sexual organisms than in asexual organisms. Okay.



[end of transcript]

Life history covers three main classes of traits in organisms: age and size at maturity, number and size of offspring, and lifespan and reproductive investment. Organisms must make tradeoffs among these traits that typically cause them to come to evolutionary equilibrium at intermediate values. Life history traits are evolutionary solutions to the ecological problems of the risk of mortality and the acquisition of food, and they are expressed in reaction norms that determine the particular traits that an organism will exhibit when its genes encounter a specific environment during development.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 10

Transcript



February 6, 2009



Professor Stephen Stearns: Okay, today we're going to talk about life history evolution, and life history evolution deals with some big questions. It's explained why organisms are small or large, why they mature early or late, why they have few or many offspring, and why they have a short or a long life.



Basically what life history evolution does is it analyzes the evolution of all of the components of fitness, all the different things that combine to result in lifetime reproductive success, and in so doing it visualizes the design of the organism as an evolutionary solution to an ecological problem. So it's fundamentally about the interface between evolution and ecology, and it is one of the places where scientists confronted the problem of how do we explain phenotypic evolution rather than genetic evolution? So this is really about the design of the large-scale features of organisms, and it brings us to ask questions about ourselves as well, of course. Why is it that we have a lifespan of about eighty years? Why is it that we're about three kilos when we're born, etcetera? Okay, so we fit into this matrix of questions.



Now here are a few world records. Biggest baby is a blue whale, twelve tons. And the interesting thing about it is that it will grow to be sixty tons in the next six months. So it's really pumping it in. And by the way, a mother blue whale, and most whale mothers, actually have muscles in their breasts so that they actively pump the milk into their offspring. Baby isn't just sucking. Baby is attached to a fire hose. Okay? [Laughter]



And look at what happens to the mom. She goes to warm tropical waters to give birth, has her baby, and then she nourishes that child until it is independent, without eating herself. Imagine how big she is, because he turns into something sixty tons. And you can imagine how cranky she is before she swims back to Antarctica to get lunch. Okay?



Then if you ask yourself, for a given body weight what is the biggest thing? It's not the blue whale baby, it's the babies--the twin babies of a bat are the largest weight of any offspring in mammals, and she actually flies with them. And in the kiwi, it has a 400 gram egg. If you take a radiograph, if you put a kiwi into an x-ray machine, take a radiograph of it, you are to imagine an egg that's occupying about two-thirds of the body cavity of the kiwi, it's got a giant egg.



The fewest offspring per lifetime of anything that's out there bearing a significant risk--and this is actually less than humans--is the Mexican dung beetle, that only has four to five babies per lifetime, which is pretty remarkable when you think about how risky you would think life would be for a Mexican dung beetle. How can it get away with only having four or five babies, if some of them are likely to die? But, in fact, it has such good parental care that it's around, and it's doing just fine, thank you, with only four to five babies.



And the most offspring per reproductive event is orchids. Orchids produce typically billions of seeds and they are extremely tiny and the only reason that they can hatch is that they have a fungal midwife that helps them. Orchid hatching is dependent upon fungi. So the mother doesn't have to put the nutrients into the seed. So she makes billions of tiny seeds. And in bivalves and codfish, they can get up to hundreds of millions of eggs per reproductive attempt. So you can see that just by comparing some numbers and looking broadly--and this is a typical thing that happens in comparative biology, it's one of the neat things about it--if you look across the Tree of Life and you see how different things live their life histories, you'll immediately start to ask questions.



You guys have all been generating wonderful questions this week. You look at that stuff and you say, "Well why are things big and small? Why do they have few babies or many babies? What has caused the evolution of all of this diversity?"



So here is the largest whale and the smallest dolphin. So this is the whale radiation. You can see that since the ancestor, there's been considerable change in body size. Here's Pipistrellus, flying with babies. Here's a dung beetle, and it's going to lay its egg into that pile of dung. That's why it's going to have an extremely well protected baby. Not too many things are going to come along and eat baby. [Laughter] And here's a kiwi with its egg. Okay? So diversity.



So in the history of ideas, life history theory and the rest of evolutionary and behavioral ecology fit about here. Darwin showed us that natural selection and descent with modification from ancestors can explain a lot, but then genetics remained a problem until 1900. Then we had the genetical reaction to that issue, which is the neo-Darwinian synthesis that basically says Darwin works with genetics. And this concentration on genetics then, in its own turn, elicited a reaction. So this is a reaction to that. And what's the role of phenotypes in evolution is the reaction to the neo-Darwinian synthesis.



So the phenotypic reaction, it's been going on for about forty years. It has a selectionist part--that is, how are phenotypes designed for reproductive success--and it has a developmental part: what are the restrictions on the expression of genetic variation? So the phenotypes are actually both being designed by natural selection for reproductive success and, in the process of their production, they are themselves editing genetic variation.



So life history evolution is the part that explains the design of phenotypes for reproductive success, and it concentrates on size at birth, how fast things grow, age and size at maturity, reproductive investment, and mortality rates and lifespan. So part of life history evolution is why do we grow old and die?



And after a lot of discussion, it was possible--this is after about twenty years of discussion--to make this simple statement: What causes life histories to evolve? They result from the interaction of extrinsic and intrinsic factors.



So the extrinsic factors are things that are influencing the age-specific rates of mortality and reproduction, and that's where ecology comes in. It's not just ecology, there's a lot of phylogenetic effects on this stuff, but the point is that if you look at whatever is affecting changes in mortality and reproduction, in age and size of the organism, you will be able to explain a great deal of what you see in the life history.



But that's not enough. There's interaction between that and factors that are intrinsic to the organism, and the intrinsic factors are conceptualized as tradeoffs among traits. The idea here is there's no free lunch. If you change one thing in evolution, a byproduct of that change will be a change in another trait. So even though you are gaining fitness through changes in one trait, almost inevitably, whatever you change is going to cause a decrease in fitness in some other trait, and this forces compromises.



So the intrinsic factors then can be looked into, and we find phylogenetic effects, developmental effects, genetic effects, physiological effects; all sorts of things. Tradeoffs in a evolutionary situation are often conceptualized as being strictly energetic. If I take calories away from my growth in order to reproduce and make more babies, then I won't be so big next year and I can't have so many babies next year. That would be kind of a standard physiological story about a tradeoff. But they can also occur in many other ways. So that would be a physiological story.



But certainly there are developmental and genetic influences on tradeoffs as well. So there's a lot of biology that's hiding behind these simple summary statements, on this slide. In the rest of the lecture I'm just going to show you how to explain age and size at maturity, reproductive investment, and aging and death. So, not too much.



This is kind of a standard statement out of life history theory, and this generic statement could be applied to clutch size and lifespan and a lot of other things. But let's just look at age and size at maturity. They will be optimal when the positive difference between the benefits and the costs--so the difference between the benefits and the costs--is maximized. And we can conceive of that as either being maximized just at a stable equilibrium point--that's kind of a simple statement, that's a theoretical statement; so that would be, okay, everybody in this species, they ought to mature at just one age and size, which is a little unrealistic. Or we can use that kind of analysis to predict a stable equilibrium reaction norm. So here we're beginning to use this idea that we got of a reaction norm.



And that one summarizes pretty easily. You're going to--whatever problem you're faced with, you're going to mature at the age and size where the payoff in fitness is going to be greatest. The problem analytically is to decide what you have to bring in to the mix in order to successfully make that prediction. You want to keep it as simple as possible, because it can get very complex, but you want to keep it realistic enough to actually be successful. So it's a balancing act.



Now with--I'm going to show you one way to do this. If we make four general assumptions, we can predict age and size at maturity. Here they are. The first one is that if you're older when you first reproduce, your offspring are going to have better survival rates, they will be of higher quality; so one reason to wait is that you get higher quality offspring. Another reason to wait is that because you've been growing for longer, you've taken longer to grow before you start to reproduce, you can have more of them, because you're bigger; especially important in plants and in fish.



However, these advantages of delaying maturity are counter-balanced by the advantages of having a shorter generation time, and you can only get a shorter generation time if you mature earlier. Let me just illustrate the advantage of a shorter generation time. I give you a hundred bucks and I tell you you can invest it in a bank that's going to give you compound interest once a day, on the one hand, or once a year, on the other hand. You all know the advantages of compound interest; you get interest on your interest. Right? A shorter generation time is the bank that gives you interest earlier; you get grandchildren quicker. Okay?



So that is basically the elements that you need to put into a quantitative tradeoff. Delaying, you can get higher quality, or more offspring; doing it quicker, you're going to get a shorter generation time and a quicker payoff. Now in a population that's at evolutionary equilibrium, these advantages and disadvantages should have come into balance. So let's see how that might work.



Here's a simple example. This is using data from the Western Fence Lizard, and what you're looking at here, this plot here, where you see these curves going up and down, that's a fitness profile. So we have some kind of trait along the y-axis; in this case it's age of maturity--along the x-axis. Along the y-axis we have relative fitness; so this is the rate at which a population of organisms with that age at maturity would grow, given what we know about the physiology and mortality rates of fence lizards.



And if we just put in one of those assumptions, which is that the bigger they are the more babies they have -- so their fecundity grows linearly with size -- their optimal age at maturity is just about twelve months. If we put in that if they get higher quality offspring as they delay maturity, given the assumptions in the model, we predict actually that they ought to be maturing at about six months. Their observed age at maturity is ten months.



That indicates that this effect is probably important and perhaps accurately modeled. This number tells us that well perhaps we don't really understand what makes for a good baby lizard. Okay? And you can see that interestingly the age at maturity is pretty strongly peaked; the fitness profile has a peak that's pretty close to one value. That means there's pretty strong selection operating on this. It's not flat.



Now if you repeat that kind of thing--and by the way, there's a bunch of math behind that; I'm just waving my hands and covering up that black box. If you repeat that for a bunch of fish species that are growing in different kinds of conditions--these are haplochromine cichlids in Lake Victoria; the painted greenling lives in Seattle; these roaches are living in Greece--and these are all cases in which very good population biology has been done for long periods of time in the field. So we know growth rates and mortality rates, and we have some estimate of tradeoffs. Then that kind of thinking says this is the predicted age at maturity and this is the observed age of maturity, and the correlation is .93.



So it looks like that way of thinking is capturing something that is not a bad reflection of what's going on in Nature. This sort of result doesn't mean you've got the right answer. You can have the right answer for the wrong reason, because this is just descriptive work, this is not a manipulative experimental study. We'll see such an experimental study later on.



However, that's not the whole story. I now want to extend that to the case when growth rates vary, and I want to introduce you to the idea that age and size at maturity can have a reaction norm. And the way I want to do that is by dealing with some incredibly blockheaded strategies. Okay? So here we have rapid growth. So this is an organism that is born down here, and it's well fed and it grows rapidly. So it gains weight well, reaches a large size. And this is an organism that grows slowly; it's under food restriction, down here.



Now let's take the blue strategy--this is a very, very simple one--and what it says is I'm always going to mature at the same weight. If that organism is growing rapidly, it matures at a pretty early age, but if it's growing slowly and it adheres to this rule, it has to wait a long time until it matures, and its problem here is that it might die before it matures. So that strategy has the cost of mortality.



On the other hand, if it's always the same age when it matures, under good circumstances, it's doing okay, but under poor circumstances it's much smaller, and therefore it can have fewer babies. And so the problem here is fecundity; it's going to not have as many babies if it does that. And so just intuitively you might think that there is some kind of intermediate compromise so that when it is not being fed as much, it changes both its age at maturity and its size at maturity.



And, in fact, this kind of thing can be calculated. This is an optimal reaction norm for age and size at maturity. They don't all look like this. Okay? This is a common one, but there are conditions under which you can make this thing bend. You can actually sometimes get them so that they go up like this, under very special circumstances.



It depends on a bunch of stuff. I don't want to trouble you with the complexities. I just want you to take home the message that you can predict what the plastic flexible response should be if evolution has come to equilibrium. And for this one, basically what this graph is telling you is this--this is the reaction norm here, these are growth curves here; so this is good conditions, this is poor conditions--and what this picture is telling is that when life is good, you should mature when you are young and big, and when life is bad, you should mature when you're old and small. Okay? That's the English take-home message, out of that picture.



Well when Nile perch were introduced to Lake Victoria, there hadn't been any Nile perch in there before, and they went bananas and ate their way around the lake--and in the process, by the way, they probably drove about 200 haplochromine species to extinction--but while they going through their initial population burst and they had a lot of food, they were about six feet long. This is the business end of a Nile perch. You can see it's a big fish.



After they had expanded in the lake, which occurred between 1976 and 1979, they ate down the population of their prey, there wasn't as much food and they didn't grow as well, and they slid down this reaction norm, and now instead of being six feet long, the Nile perch in Lake Victoria are about that big. They still form a fishery and people are still making money on selling Nile perch fillets, but they're much smaller. And that was a predictable thing. Okay? And this will happen whenever population densities change.



Back in the 1930s and 1940s, there was a huge sardine fishery off the coast of California. John Steinbeck wrote novels about it, short stories. There's a book called Cannery Row that talks about the Monterey Bay sardine canneries. In the 1950s that fishery collapsed, not because of over-fishing, but because of changes in the oceanic conditions where the baby fish were growing up. At the time that it collapsed, there were sardines that had been born under better conditions and started to grow, and then all the competition went away; nobody else came along because all the baby sardines were getting killed by bad conditions out in the ocean.



Just before the fishery folded and there were no longer enough sardines to catch, the fishermen in Monterey were catching female sardines that were one meter long. So they had gone in the other direction, they'd gone up the reaction norm. These things are predictable as population density changes.



I'd like to give you one more example, and it has to do with the issue of whether or not the mammals died out because of bad weather, or over-hunting. Dan Fisher, who's a paleontologist at the University of Michigan, has recovered a lot of mammoth bones from a Native American mammoth slaughterhouse that was outside of Ann Arbor. They used to kill the mammoths and then store them under ice, in a lake, over the winter, so that the other predators wouldn't get the meat, and there are a lot of mammoth bones very close to Ann Arbor. And you can ask yourself--when you look at a mammoth bone, you can tell how big the mammoth was and whether or not it is mature, because the bones of all mammals undergo a change when they reach maturity.



Now if it was bad weather, then they would've been growing slowly, and they should've been small and older when they matured, according to the reaction norm. If it was hunting, then just like the California sardine, when the population density drops, each individual has more to eat, and they should have been big and young when they matured. Do you think they were old and small, or big and young? How many for old and small; bad weather? A few. How many for young and large; hunting? Most people believe the over-kill hypothesis. Yes, they were young and large, and some of them had arrow points embedded in their ribs. So you can use that for various things.



This is what that model tells us about human females. These are some pretty theoretical growth curves for human females under poor conditions and under good conditions. We actually have data on how female age and size at maturity has changed. There are measurements on women working in industrial squalor in North England, in the nineteenth century, and there are good records measured on Hutterite colonies in North America in the twentieth century.



The nineteenth century women were poorly nourished. The twentieth century women were well nourished. They moved right up a reaction norm. They got younger and bigger when they matured; and it was about four year's difference. So they went--there are various measures of when a woman is--physiological measures--but they kind of all move together. So it's about a four-year advance, earlier maturity in the twentieth century.



And this other line here illustrates another point that I want you to take away from this. If modern medicine were to keep juvenile mortality rates as low as it currently does, then it would cause a further shift in age at maturity in humans, and that shift is represented here. This probably would take somewhere around 5 or 10,000 years to occur. This is the evolutionary genetic response; this is the immediate developmental response to better nutrition; and this is the evolutionary genetic response to a drop in juvenile mortality rates. The whole reaction norm evolves; it will move up and down. It's embodying an evolutionary set of rules of thumb, contingent decisions--if I'm well nourished, do this; if I'm poorly nourished do that--and those things evolve.



Okay, now the second major life history trait is once you've matured how many babies should you have, and how big should they be? You want to be an orchid with billions of tiny ones, or you want to be a kiwi with one big one? Well the ideas on this go back to David Lack. David Lack was the man who more or less created the idea of Darwin's finches in the Galapagos.



Darwin's finches, as a concept, emerged in the middle twentieth century. They were never called Darwin's finches before David Lack went to the Galapagos, studied them, came back and wrote a book called Darwin's Finches. It was 120 years after Darwin had been there. And he went on to become head of the Edward Gray Institute at Oxford, which is an ornithological institute and one of the best places in the world to go if you're interested in bird biology and you're not working with Rick Prum at Yale.



So what David said basically was this. If nestling survival decreases as clutch size increases, then an intermediate number of eggs produces the most fledglings. The idea behind that was this. If you make too many babies, you won't be able to feed them. There are only so many hours in the day. You might be able to work as hard as possible and not bring off a clutch of say ten babies, but you could do quite well with five.



Now I'm going to show you that he was wrong on the details, but he got the main point, which is that fitness is often maximized at intermediate reproductive investments, particularly in organisms that reproduce more than once per lifetime. You don't do it all now, you hold some back, and you actually do better if you spread it out.



So if we then take Lack's idea, and we make a simple model out of it--basically what he was saying is this. As clutch size goes up, well that just means that eggs go up, but if survival goes down, as eggs go up--this is the per egg survival probability; basically this is saying that if you only laid one egg, you'd have very good survival, and if you lay ten eggs they all die.



You can turn that into an equation for how many fledglings do you get for a given number of eggs? Well it's going to be 1 minus a constant, times the number of eggs you lay, which means, if you multiply that out, that you've got a quadratic term here in eggs; and that is what leads to the parabola, it's this quadratic term that means that as clutch size goes up, the number of babies that you get out of it has a parabolic form with an intermediate optimum.



And you then just do the standard basic calculus thing of taking the first derivative, setting it equal to zero. It tells you that this point right here is going to be at 1/2C, in this equation, and if C is 0.1, this optimal number of eggs will be 5, and the number of fledglings that you get out of it will be 2.5. Of course, you never get 2.5, but that's just because the model's continuous and the eggs are discontinuous.



Well if this is the case, if birds are laying the optimal clutch, then a larger or a smaller clutch should have lower fitness. Basically all we're saying is that if we were able to take a bird, and she wants to do this, but we give her either fewer eggs or we give her more eggs, then she should have lower fitness. This should be the best, which she naturally does, and we perturb that, she should have less fitness.



This was done on kestrels in the Netherlands by Dutch ecologists, in a rather remarkable study. A kestrel is a sparrow hawk, and these animals live, these birds live for several years, and the Dutch ecologists actually followed them long enough to count the grandchildren; they went three generations.



So, this is the setup. They reduced the size of 28 clutches, enlarged the size of 20 clutches, and in 54 clutches they took the eggs out and put them back again; those were the controls. And if you just look at this, it looks like these birds should be laying more eggs, because if you look over at the enlarged clutches, they've been able to change the brood size up by 2.5. They've been able to get more fledglings out--they've gotten nearly two more fledglings out of the enlarged clutches--and the reproductive value of that clutch, which is how many grandchildren do I get out of that clutch, is higher.



So it looks like these birds are blockheaded, they should be laying more eggs. But that's only looking at what happens that season. While they were examining these birds, one of them, Serge Daan is a good physiologist, and so he did the experiment with doubly labeled water. He wanted to find out how hard the birds would work, and they were coming into nest boxes.



So mommy and daddy kestrel fly into a nest box with food for baby; evil Dutch ecologist, sitting in back of the nest box, takes food away from baby. Baby cries. Baby gets hungry, mommy and daddy work harder. Evil Dutch ecologist takes away food. Mommy and daddy work even harder. How hard do mommy and daddy work? Mommy and daddy work about eight hours that day--daylight's about sixteen hours a day in the summer in North Holland--and they hit a rate of physiological output which is nearly four times basal metabolic rate, which is what Lance Armstrong puts out on the Alpe d'Huez in the middle of the Tour de France.



So the Dutch ecologists basically forced these birds to work as hard as a peak human athlete would, and then they quit after eight hours, because they didn't want to die. And then the Dutch ecologists gave the babies their food. Just so you don't have nightmares about that. Okay?



So that introduces parental survival. If you increase the clutch size, the parents died the next winter at a higher rate, because they worked harder. Okay? And if you add all of that up, the residual reproductive value of the rest of their lifetime; the number of grandchildren they would get out of the rest of their lifetime was highest for the reduced broods, intermediate for the control broods, and strikingly lower for the enlarged broods, because of this effect. If you die before the next year, you get zero babies next year.



So if you look at their total reproductive value, which is the value they got this year, plus the value they got in the rest of their life, it's highest for the control group, and if their clutches were enlarged, they had one grandchild less, and if their clutches were reduced, they had a half a grandchild less. Which has an interesting take-home message. These Dutch kestrels know what's best for them. They lay the right number of eggs. That's the control group.



So the take-home points basically are that what's going on here is that clutch size is trading off with an important fitness component, but it's not fledgling survival, it's parental survival. In this case--it's different in other species--but in this case the reason that they don't lay more eggs is that they themselves are more likely to die; not that their offspring are more likely to die. And these kestrels are optimizing their reproductive investment with a clutch that's of intermediate size. They could lay more eggs but they don't. They know how many to lay.



Okay, so that's just one example of clutch size analysis. It's a big literature, there's a lot of experiments on this. Now let's go to lifespan. So I'm taking you through the major life history traits from birth to reproduction to death. In Fragment of an Agon, T.S. Eliot wrote, "Birth, reproduction and death. That's all the facts, when you come to brass tacks, birth and reproduction and death." He wrote that in the 1930s I think. I didn't realize that T.S. Eliot was a behavioral ecologist; evidently he was.



So reproductive lifespan, under this kind of analysis, is a balance between selection that increases the number of reproductive events per life--you live longer, you can reproduce more--and effects that increase the intrinsic sources of mortality with age. And it's this idea that there's an evolution of aging or of senescence; there's an evolution of the body falling apart, as a byproduct of something, which is the key feature of this part of life history theory.



So the first kinds of selection pressures are going to lengthen life to give you more reproductive opportunities, but if there are byproducts that are causing intrinsic increases in mortality rate, those will shorten your lifespan. So these things then come into some kind of balance. Any increase in intrinsic mortality rates, or decrease in reproductive rates with age, is called aging or senescence. So now we're talking about why people fall apart when they get old, and why organisms age and die.



To do that I need to introduce you first to the way selection operates at different ages. Selection is quite age specific in its impact. Any selection pressure that lengthens life is going to be one that decreases the relative contribution to fitness of offspring, and increases that of adults.



So if an adult has survived to some intermediate age, and juvenile mortality in that species is pretty high, then the adult represents a relatively improbable event that's quite valuable, and if it's making babies in that environment, each of them has a relatively low chance of surviving to be that big and that old, and therefore there is a certain fitness advantage in investing in the preservation of that adult, because it's unlikely that you'll get another one up to that state.



The things that will do this are lower adult mortality rates and higher juvenile mortality rates. So if life is relatively good for adults and pretty risky for juveniles, and infants, then you're going to get the evolution of a longer lifespan.



But in contrast, if adult mortality rates increase, then organisms should evolve more rapid aging, basically because there really isn't much point in maintaining a body that's going to be dead anyway for other reasons. Why should I take away from my reproduction and invest it in say disease resistance, or running away from predators, if I'm not going to be able to avoid them anyway? Then I should make more babies. Okay?



So those are the basic ideas. And I'd like to illustrate a little bit of the math behind this, with a pictorial model. So this is why senescence evolves. I'm going to use the fruit fly Drosophila as the model organism. We're going to start this thing off, not when it's an egg, but when it ecloses and is an adult, and we're going to say that our model has no intrinsic mortality at all. So this one doesn't age; this is our baseline, this is what happens if an organism doesn't age.



Its risk of dying is 20% per day, and every day it lays ten eggs. Okay? So on the first day it gets ten eggs. On the second day 80% of them are still around, and each of them lays ten eggs, and on the third day 64% of the original are still around (.8 times .8), ten eggs, ta-da ta-da. And this thing is potentially immortal. Okay? So it can just go on pumping out the eggs, if it survives for as long as ever; and its probability of survival isn't changing with age, it's 80% each time. This one gets 50 progeny. We do that just by using an infinite series. Okay? And the numbers were set up to give you a nice simple output. Okay? The numbers are cooked. So this one gets 50.



Now, what happens if everybody dies between the nineteenth and the twentieth day? That one gets 49.3. That's all the difference that death at old age makes. And this is in a case where there's no senescence. Right? This is kind of like light bulbs failing or something like that.



However, now let's throw in a little life history tradeoff, and it's a really small one. This genotype here, because it can lay eleven instead of ten eggs, on the first day of life, dies, between the nineteenth and the twentieth day, it leaves 50.3 progeny. It has a .6% fitness advantage. If we introduce this genotype into the populations of the ones that live forever, it will take over. There won't be any immortal flies anymore. There will be flies that have evolved a shorter lifespan because they had a reproductive advantage early in life and it didn't take much of one to do it.



As you contemplate your own mortality, I hope you realize that the Drosophila example in fact is non-trivial; it's giving you an important message. This is the strength of selection on further survival in human males in the United States in the year 1960, calculated from real demographic data from the U.S. Census. This is the partial derivative of fitness with respect to further survival. And it's a very interesting picture.



What it shows you is that as soon as you become a teenager and you have some probability of surviving in that human population, your fitness starts to drop, because as soon as you've had a baby, you have some probability of grandchildren. And it shows you that after the age of 46, evolution doesn't care if you're there anymore, from the point of view of getting grandchildren. As someone who is out here, I would like to congratulate all of you. There's a reason I look different from you.



Now this way of looking at aging basically says that aging is a byproduct of selection for reproductive performance, and the reason that it occurs is that there's an accumulation of a lot of genes, and they have positive or neutral effects on fitness components early in life, and they have negative effects on fitness components late in life. The positive effect is called the antagonistic pleiotropy hypothesis. The idea is that the gene has two effects: good early and bad late. It's like that one that gave the fly one more baby, on the first day of life, but killed it off at the nineteenth day of life. And neutral effects early and negative effects late is called the mutation accumulation hypothesis.



And these two hypotheses formed sort of the intellectual basis of research on the evolution of aging for quite awhile, and they turn out to be not too productive. It looks like--in fact, most of the cases that have been well investigated, suggest that it's positive effects early and negative effects late; not neutral early and negative late. Okay? But it's hard to distinguish between these sometimes.



A general take-home point is this: that organisms age is actually the best evidence we have that it's the replication of genes, not the survival of organisms, that is the object of evolution. So that gives you strong empirical evidence that a gene-centered view of evolution is in fact empirically correct. This is extremely discouraging for the organisms that have consciousness and the ability to analyze a situation. [Laughter]



So, a bit of experimental evidence. By the way, there have been five or six experiments like this. I'm just showing you because this is the one I did. We had two treatments. We had high and low adult mortality. And if you followed the logic so far, then you already know that if you apply high adult mortality, then the organism should age rapidly, and if you apply low adult mortality, they should evolve to age more slowly. So if you make the environment risky, why try to invest in surviving, because somebody's going to kill you anyway? And in this case it was a Swiss laboratory technician that was doing the killing, but one can imagine that it might have been a lion or something like that.



The result is that after five years, which is about 70 to 110 generations, in these flies, aging evolved as expected. The higher extrinsic mortality rates have produced shorter intrinsic life spans, and the change was about five days. It's convenient that a day in the life of a Drosophila is about a year in the life of a human. So that gives you some feel, some kind of intuitive feel for what this means.



Basically what that means is that if we had started applying this strength of selection at the time of the Trojan War, we would have produced a response in the human population of about five years by now. Okay? Just to put it back into the human time scale. There's a paper here. You can go read about that if you want. It gives you an entry into that literature.



To summarize today's lecture, all the major life history traits--age and size at maturity; number and size of offspring; lifespan; reproductive investment--are involved in tradeoffs, and that causes them to come to evolutionary equilibrium at intermediate, not at extreme values. They are all under stabilizing selection caused by tradeoffs. Age and size at maturity, number of offspring per birth and per lifetime, and lifespan and aging have all evolved.



I'll just riff on this for a moment, to tell you how you've changed, compared to chimpanzees and bonobos. Humans live a bit longer, about oh twenty years longer. The unique human life history traits that appear to have evolved since we shared ancestors with chimpanzees and bonobos are menopause, which does occur, but rarely, in zoo chimps, and is almost never observed in the wild. The most striking thing though is that we can have babies twice as fast as they can.



The average time in a Neolithic or hunter-gatherer society, between births is two years, in humans, and in chimps it's five to six. That, despite the fact that human babies are much more helpless and need a lot more parental care when they're born. So, in fact, humans have somehow managed to almost double the reproductive output of chimpanzees, and it appears that they've done it through social interaction.



So family members help raise the kids. Sometimes even partners help raise the kids. Grandmothers help raise the kids. But there's a lot of help. And so the reason that the inter-birth interval in humans has been shortened dramatically in the last five or six million years is because we have become a much more highly integrated--we have a much better integrated family life.



The evolution of all of these traits can be understood, in general, as an interaction between extrinsic ecological conditions, that determine mortality rates, and conditions inside organisms to cause tradeoffs. So if you're looking for a general explanatory structure, it is that the environment poses problems, and when you answer that problem with a solution, you are forced to make compromises; and we know usually which kind of compromises, and we are now in a position to say if you're looking in the environment you should look for these kinds of factors.



Okay, next time we're going to extend this framework into a particular part of life history evolution called sex allocation, and how investment is divided between male and female function, and when it pays to switch sex and to be born as one sex and turn into the other.



[end of transcript]

Sex allocation is an organism's decision on how much of its reproductive investment should be distributed to male and female functions and/or offspring. Under most conditions, the optimal ratio is 50:50, but that can change under certain circumstances. Sex allocation determines what sexes sequential hermaphrodites should be at each part of their life as well as how simultaneous hermaphrodites should behave. Some species have more control over the sexes of their offspring than others, and adjust the sex ratios of their offspring depending on the environment and conditions.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 10

Transcript



February 9, 2009



Professor Stephen Stearns: Okay, today we're going to talk about sex allocation theory, and I would like to begin by reminding you of where we're at in the course. We're in the middle of micro-evolutionary evolutionary biology, the micro part, and we are now applying the ideas that we've developed to try to understand the design of phenotypes for reproductive success.



This portion of the course basically started with the evolution of sex, and then we saw that sexual- the evolution of sex opened up all sorts of possibilities for genomic conflict in evolution, and that gave us the image of the organism as not necessarily being optimized or just adaptive. The organism can be viewed as a composite, and the parts of the composite can be in conflict with each other.



With life history evolution, we've more or less shifted back to a view of the organism as being optimized in some sense. I think we saw that most clearly with the kestrel parental investment and investment in clutch size, and in things like optimal reaction norms for age and size at maturity. Now, when we go to sex allocation, we are looking again at how to optimize the life history. But the issue now is how much should be invested in male function and how much should be invested in female function? And this opens the doorway also to alternative explanations.



Some of these patterns that we're going to be looking at can be seen as the result of more or less an optimality argument, that this is the best way it could be done, given the constraints on the system, but in other places it's possible that there are fundamental conflicts going on and that nobody's winning, that everybody's making the best of a bad job. And I think that you'll see some of that when we get into the frequency dependent parts of sex allocation.



So sex allocation theory is actually a part of evolutionary ecology which has been extremely successful. It predicts the distribution of reproductive effort among male and female offspring, or between male and female function. It makes a lot of successful predictions.



There is a theorem at the heart of this part of biology called the Shaw-Mohler theorem, which is very general in the way it's formulated, and it unites many previously unrelated phenomena. So the successful predictions, and the bringing together in a single explanatory framework of a lot of stuff that was previously seen as unconnected, is a characteristic of any good scientific theory. After all, that's what the Periodic Table does in chemistry; that's what Newton did with his Laws of Motion. So this is a good example of success in evolutionary theory.



In order to get into this field, we need to have a little vocabulary building, just so you can operate in the literature. If you're a botanist, you call organisms that have separate sexes dioecious, and if you're a zoologist you tend to call them gonorchoristic. The default condition in most flowering plants is that they're hermaphrodites and they have both male and female parts in the same flower. But there are some striking exceptions. Papayas have separate male and female sexes; holly have separate male and female plants; and so forth. So there are certainly dioecious plants. The default condition in most animals is that the sexes are separate. So the default condition is different in most flowering plants and most higher animals.



Now if we're dealing with sequential hermaphrodites, then they can be either protandric or protogynous. We call them protandric--so first male, pro andros--if they're born as males and change later to females, and we call them protogynous if they are first females and then change to males. Okay? The only human in mythology, at least in Western mythology, who has done something like this was the Greek sage Tiresias, who was a prophet during the Trojan War and is said to have been, in his lifetime, both male and female, having been changed by the gods, rather than by his hormones, and was able to report on what it's like. You might want to go back and check.



Now for the purposes of sex allocation theory, we define female function in a number of different ways. Okay? It could either be the proportion of offspring that are female; that could be a lot or a little. It could be investment in female versus male offspring; so you have equal numbers of both but you decide to invest more in offspring of one sex than the other. Or in a sequential or simultaneous hermaphrodite, it's the proportion of lifetime reproductive success gained through reproduction as a female. So female function can have to do with timing, with investment and with numbers; male function is defined similarly.



So there are some very basic questions about sex allocation. One is, what's the equilibrium sex ratio? What should we expect to see in a population that has separate sexes? Another is if the species we're dealing with is a sequential hermaphrodite, as what sex should that organism be born, and how old and large should it be when it changes sex? If it's a simultaneous hermaphrodite, then what would be the allocation to male and female function in simultaneous hermaphrodites? We're not going to talk about this very much today, but I would like to give you just a little bit of natural history.



There is a lovely Caribbean fish called the Hamlet, which is a simultaneous hermaphrodite, and it can make eggs and sperm at the same time, and they mate every day, and when they get together to mate, there's the issue of who should be male and who should be female for this mating? And the eggs are big and expensive, and the sperm is small and cheap, and so you don't want to get cheated by somebody who never wants to be the female and just makes sperm. So what they've come up with is a mating pattern where in order to mate at all, they more or less insist that they trade roles and do it about ten times, so that they equal out. So in the course of twenty minutes, they will switch back and forth from being male to female, and then each of them will have put out roughly the same amount of eggs and the same amount of sperm. So I just wanted you to have that in the background as one of the sort of paradigmatic examples of how simultaneous hermaphrodites have solved that issue.



And then there's the interesting issue--and by the way, this is something I stuck in here this morning, so those of you who have printed out your PDFs, this is new--when should differential investment in offspring of each sex depend on social status? And I stuck this question in here, because in fact the lecture deals with that. We're going to come to the Trivers-Willard hypothesis, and we will see that social status, or physiological status, really does affect sex allocation quite a bit.



So these are all aspects actually of one problem, and that problem arises because of this key fact. Every diploid sexually produced zygote is getting half of its autosomal genes from its father and half from its mother, and that's also true of the sequential and simultaneous hermaphrodites; okay, that's what it means to be a sexual diploid. And that has a consequence. It means that the fitness that's gained by an individual through male function has to be compared with fitness gained by other individuals through male function, and similarly for fitness gained through female function. In other words, male and female function are equivalent paths to fitness.



Now in a number of circumstances in evolutionary biology it is advantageous to use what I call 'the looking backwards ploy' to develop an intuition for why this is true. Think about the genes in your body--you got half from your mom and half from your dad--and look backwards to where they were sitting in grandparents, great-grandparents, great-great-grandparents, and so forth. And if you go through that branching tree, going backwards, you'll see that in each generation half of them were coming down through a female and half of them were coming down through a male, and as they go forward, into the future, it's always going to be, on average, half of them coming down through a male and half of them coming down through a female.



This means essentially that this statement, male and female function are equivalent paths to fitness, is something that you could derive by putting out the whole genealogy of the family tree and just counting the number of times that genes had occurred in male or female ancestors, and you would discover that it was 50:50. Okay? [Request to turn off cell phones]



Okay, we start this kind of analysis with the default condition, which is the 50:50 sex ratio. That's a photo of Ronald Fisher. He came up with this idea. He's one of the people, by the way, who demonstrated that Mendel's laws are consistent with natural selection. He also invented quantitative genetics, and he invented the analysis of variance in statistics. He was a total autistic geek and a nasty father, and his daughter wrote a really fascinating biography of what it was like to grow up with this guy, who was a fulltime, 24/7 biologist, and who kept all kinds of plants and animals around the house and kept breeding them, but was not what you would call a terribly empathetic, emotional person.



And he also was a guy who was nearly blind, but who visualized most problems geometrically. He was very powerful mathematically, but Fisher essentially saw things geometrically that most people see algebraically. So his theoretical writings can be opaque at times. But, this idea is pretty straightforward:



If males and females are equally good at producing male and female offspring, at all ages and sizes--so everybody's pretty much on a level playing field--if mating's at random, in a big, large population, that's thoroughly mixed, then the sex ratio should evolve to 50:50 male/female offspring. Basically the reason that's true is that the rarer sex has an advantage. The sex ratio is adjusted until neither type is rarer than the other, and that's probably the most basic frequency dependent equilibrium in biology.



You can see why that would be true if you imagined that you were a mutation that produced only male offspring in a population that was otherwise producing all female offspring. You would then have the only males in that population, and all of the offspring in the next generation would be carrying your genes. You would increase in frequency.



You can see how it would work in the other direction, if you do this kind of mutation invasion analysis, by asking yourself, what would happen if everybody else in the population was male, or everyone else in the population only produced male offspring, and you're the only one to make female offspring? Well you get--all of the grandchildren are yours. Okay? So you increase from the other direction. So if you imagine populations that are being invaded by these different alternatives, they come together at the middle, and it's only at 50:50 that there's an equilibrium.



This may be why sex chromosomes evolved. Okay? We have sex chromosomes, we have an X and Y chromosome. That guarantees 50:50. But before there were sex chromosomes, there was sex, and there were evolutionary dynamics, and it may be that this is why organisms with sex chromosomes have evolved.



There are many other ways of determining sex. You don't have to have sex chromosomes. Crocodiles and turtles do it with temperature. Sometimes parasites determine what sex you are; Wolbachia will do that. Sometimes sex is determined by a quantitative process of many genes, rather than having a sex chromosome.



So this process, which we find to be almost intuitive because we have sex chromosomes and that's what our population does, in fact is a special case. But it appears that it would have evolved out of this kind of a situation: big populations with fairly equal opportunities for everybody. If these assumptions are violated, we get changes in the optimal sex ratio, and it's the Shaw-Mohler theorem that predicts what would happen when these assumptions don't hold. So let's have a look at it.



A mutation will invade a population if it can increase fitness through one sex more than it decreases fitness through the other. And if we state that as an inequality, the change in male function divided by average male function, plus the change in female function, divided by average female function, needs to be greater than 0. Here, little-m and little-f are the average fitness through male and female function in our resident population. So we're starting just at some starting point in evolution, and there's an average male and female function, and a mutation pops up that changes male and female function.



So its change is the critical thing. Is it changing one of them enough to compensate enough for the other? So if the percent increase in fitness through one sex is greater than the percent decrease through the other sex, this mutation will invade, and that will go on until a new equilibrium is reached. So this is more or less the invasion criterion. We're going to see three cases in which it works pretty well. There are more, but I've just selected three that are fairly dramatic. One is local mate competition; the next is sequential hermaphrodites; and the third is social rank in sex allocation.



So the local mate competition one is one that you're actually already familiar with; I've mentioned it. I will also give a second species, a mite, that does something like this. So what would the sex ratio be if all of the grandchildren stem from matings between brothers and sisters? Well you would make one son and as many daughters as possible. And to get there from a 50:50 sex ratio, basically you can see, I think, that if--we can go stepwise--if the fecundity of this creature--it's a mite usually or sometimes it's a wasp--the fecundity might be say twenty offspring, and if it was at 50:50 sex ratio, then the average mite in the population would be making ten sons and ten daughters.



But if all the sons are only inseminating only those daughters, then anybody that made eleven daughters and nine sons would have more grandchildren; twelve daughters and eight sons would have even more grandchildren; and so forth, until you get down to nineteen daughters and just one son, and that one son inseminates all nineteen daughters, and the nineteen daughters are making almost twice as many grandchildren as the ten daughters would have. So they're just gaining all the way down, to the point where there's just one son.



And that is exactly what Acarophenax does. It's a haplo-diploid parasitic mite--haplo-diploid means that the males are haploid and the females are diploid--and there's incestuous fertilization inside the mother. So the one son inseminates all of the daughters, and then once that's accomplished the son dies and the daughters eat the mother, from the inside. So the curse on the House of Atreus was peanuts, compared to this.



This is what these things look like. This is a straw itch mite, and any of you who have been out in August, cutting the lawn, and then had little bites on your legs, were probably getting bitten by this thing. It makes 98% daughters, and it has that kind of lifecycle. Okay, so that is the case where the Shaw-Mohler theorem works perfectly. A mutation invading this population is increasing the number of grandchildren by increasing female function, and they are not losing anything in male function because that one son is still capable of inseminating all the daughters.



Now if we go to sequential hermaphrodites, it's useful to think of it as--this would be either an age or a size advantage model; the size advantage model is probably the more intuitive way to think about it--and this model is used to answer the question, into what sex should a sequential hermaphrodite be born; so what should the baby be, and then how old and how large should it be when it changes sex?



And the size advantage model basically sketches out lines of fitness, increasing with size, but they increase at different rates, and basically the argument is you should be born into the sex that has higher fitness when you're small and then you should change into the sex that has higher fitness when you're big, and you should change at the point where the lines cross.



And if this line is higher here for females, and higher here for males, we have protogyny, and if it's higher here for males, and higher here for females, we have protandry. So you should be born as a male, if your fitness as a male when you're small is greater, and then change into a female, and you should be born as a female and change if the biology dictates that your fitness is higher when you're big, as a female--as a male.



And the reasons for this are both physiological and social. The default condition actually is that small things do just fine as males, if there aren't any social dominance interactions, because a small male can still make a lot of sperm. But the fitness advantage switches to being a female when you're large, if there aren't social interactions, because a big female can make a lot of eggs.



A lot of this analysis is done in fish, and the default condition is pretty well described in a lot of fish. Small males do just fine in matings if there aren't complex social interactions, if you don't have to fight in a dominance hierarchy to get to a mating. And big females can make enormous numbers of eggs. A big female codfish, a six-foot long female codfish can make 100,000,000 eggs. A big grouper can make 100,000,000 eggs.



So, let's go through a case of protogyny, and one of the better analyzed cases is the blue-headed wrasse. By the way, for those of you who are snorkelers or divers, all the members of the wrasses and the parrot fish families are sequential hermaphrodites, and they are just about all protogynous--so they're born as females and change to males--and all of the members of the grouper or sea bass family, the Serranidae, are protandrous; so they're born as males and they change to females. So if you see a big lunking grouper, it's going to be a female, and if you see a big parrot fish, it's going to be a male.



And some of them, as you'll see in a minute, look rather radically different when they change sexes, and these are fish families in which figuring out that they were actually just two different sexes of the same species, rather than two different species, took a long time, and some of the changes in morphology and color and behavior are really rather remarkable.



So in Thalassoma, the bluehead wrasse, that's a case where they are born as females and then they change sex and turn into males, and when people first started doing experiments on this, they went out and they pulled the dominant male off of a reef, and the dominant female basically started behaving as a male within twenty-four hours, and within about six weeks she has changed color and she has changed the physiology of her gonads and she's turned into a male and she's functioning and producing sperm and mating perfectly successfully as a male. It takes a little while to change. It doesn't happen right overnight.



And actually it's a little bit more complicated because there are two options. You can actually, in this fish, be born as a female and then turn into a male, or you can be born as a male, as a initial-phase male, and then turn into an adult dominant male. And the initial-phase males are female mimics. They make their living by sneaking fertilizations off of dominant males.



The way that sex works in this species is that that they live on patch reefs, or sometimes they live on a larger reef; and you'll see in a minute that the size of the reef makes a big difference to their lifestyle. They normally swim up to spawn near sunset on the down current side of the reef. When they spawn and their fertilized eggs then are out there, in the ocean, the current will--if they've done it right--the current will carry the eggs away from the reef, because if the eggs settle on the reef, the reef is a forest of open mouths. A coral head is basically a whole bunch of little hydra, just waiting to grab onto anything that falls onto it. And so the fish do their reproduction at a time of day when planktivores will not easily see their eggs, and in a water current that carries the eggs away from the reef.



And the way they do it is that they come up off the reef and they swim up in the water column near the surface, and one of these dominant males will swim up with a whole school of females with him, and he will go through a dance and spawn, and he will release his sperm and they will release their eggs. And if there is an opportunity, one of these initial-phase males will sneak in, and because he looks like a female, he won't get beaten up, by the big male, and he will release his sperm and grab some of the fertilization opportunity. So there's an interesting question: how many should be initial-phase males and how many should be initial-phase females?



Well that's where the ecology and behavior comes in. These big, lunking, dominant, terminal-phase males can actually police a harem, on a small reef, and they can actually police an area which is maybe the size of this piece of furniture up here, or down to about half that size.



If it gets much bigger than that, then the females actually are just wandering around foraging, looking for food, and a female could wander down to this end, and if there was an initial-phase male down at this end, he could grab copulations, because there might be disruptions, as they go up at sunset, and that the number of females would have arisen to the point where the dominant male couldn't control all of the initial-phase males. So basically the idea is that if the reef is small, these guys do well. The bigger the reef gets, the better these do. And you can interpret SF either as success in sneaking fertilizations, or in some slightly less polite terminology.



So this is some field data from Panama, and it shows you what proportion of the males are actually initial-phase males. Remember I said that you would expect them to do better on the large reefs, and you would expect the dominant males to do better on the big reefs. And this axis down here is 1/square root of local population size; so actually populations are getting bigger in that direction, along this axis.



So in fact if you just--the data's fairly noisy, the transformation down here does tend to squeeze the data together a little bit, but there is a significant effect of reef size. If you're on a small reef, it's mostly terminal males. The larger the reef gets, the bigger the population gets, the more initial-phase males there are.



Now how do they know whether they should be an initial-phase male or an initial-phase female? These guys, remember they go out and they live in the plankton, and then they come back to a reef. And there they are, they're just a tiny little fish, and they're dropping down onto a reef, and from their perspective--after all, if you're just one centimeter long, you don't really know if you're on a reef the size of this room or on a reef the size of this table. So what cues could it use to decide what kind of reef it's on, and is it using a genetic cue or is it a developmental one?



Well, it's really not plausible that this kind of switch would be purely genetic, because if it were purely genetic, then you would be the kind of fish that your parent was, but you might end up in an environment where that way of living was not appropriate, because you're being spread out over hundreds of kilometers out there in the plankton and then coming down on reefs of many different sizes.



So there's some evidence that the larvae are choosing their sex based on density. If you rear them in isolation, the juveniles are almost always differentiated as females. So it's like the first one in on the reef, the default condition is to be a female, and that is regardless of whether they came off a reef with lots of primary males or with a few primary males. So it doesn't appear to be that that's an inherited condition.



But if you have them reared in groups of three, one individual usually differentiates as a primary male. So as the population size, the cues of population size start to accumulate, some of them become primary males rather than primary females.



So this seems to be an environmentally sensitive, developmental strategy, and it's probably evolved in response to variation in reproductive success of primary males and populations of different sizes. That's a fairly stringent logical condition; and again the looking backwards ploy is important.



This would never have evolved if the genes had always been experiencing reefs of the same size, with similar social conditions on each reef. You only get a developmental switch like this evolving if there has been a regular alternation of social conditions for those young male wrasses to encounter, and if that has been the case for long periods of time in the past, then the ones that have been able to adjust appropriately will have left more grandchildren; and that appears to be what's going on here.



So if you would like, if you're interested in this kind of thing, this is a good paper to get you into that literature. And remember, if you're in ISI Web of Science, you can both look backwards and look forwards. You can look at all papers published in 2008 that cite this paper that was published in 2006, for example, and you can do that with any other question that you're asking.



Now, what about a case of protandry? Well this is a case that shows the default condition when there really isn't very much complicated social life. This is a mollusk and it lives on the Connecticut coastline. And if you go out to Hammonasset State Park, which is up by Madison, and you walk down the beach, your shoes are crunching on the shells of Crepidula fornicata; that's basically what the beach consists of is the shells of Crepidula fornicata.



And these guys are born as males and grow up and change over to being females, and they go through a stage where they're both. And, in fact, they have a penis that extends downward, and so the males are actually inseminating the hermaphrodites that are in the middle, and the hermaphrodites in the middle are inseminating the female that's on the bottom. So Crepidula forms a daisy chain as a standard part of its life history. This is how these things live, and you can see the progression just sitting there in one clump, as they go through their life.



Okay, so the Shaw-Mohler theorem actually tells us quite a bit about the main questions of sequential hermaphrodites. Remember they are: as what sex should I be born, and at what age and size should I change sex? And by the way, the existence of sequential hermaphrodites leads us to certain puzzles. There are many, as you'll see in a minute, there are many mammals where it would make a lot of sense to be a sequential hermaphrodite, but evidently we don't have a reproductive system that's flexible enough for that to have evolved. And I think you'll see--but just stick that in your memory for a few minutes, because you're now going to see a few mammals that would make more sense to me as sequential hermaphrodites.



We'll get into that with the Trivers-Willard hypothesis. So again this is Bob Trivers, and with a guy named Willard he came up with the idea that in a polygynous species, a low ranking female, or a female in poor condition, should have female biased litters or clutches, because their daughters can always have offspring. Females in these circumstances are the limiting sex. You do not have to be a highly competitive female in a polygynous species to get inseminated. There's going to be some male that's going to get you pregnant.



On the other hand, high ranking females, or females in good physiological condition, should have male-biased litters or clutches. The reason for that is that their sons can only have offspring if they can dominate. So you're not going to invest in a male offspring unless you're pretty sure that it's going to grow up and be able to actually win competitions. So the examples we'll look at are red deer and chimpanzees, and at the end I'll mention the German farmers. Okay?



So in red deer on the Island of Rhum, in Scotland, where Tim Clutton-Brock and Loeske Kruuk and Josephine Pemberton and others--Fiona Guinness--have studied them now for thirty years, they have followed many individuals, from birth to death, and documented their social rank and their reproductive success and many aspects of their behavioral ecology. There is a great deal to be learned from following individual organisms from birth to death, because the variation you then see in their lives tells you a great deal about the selection pressures that are operating on them.



And what they observed was this. Here over here, on the y-axis, you've got lifetime reproductive success of male and female offspring. The closed circles are the sons, and the open circles are the daughters, and this is the social rank of the mother down here--this is subordinate and dominant--and this straight line here is drawn just for the black dots, for the sons. And what you can see is that there is really not very much influence of social rank on the lifetime reproductive success of daughters, but there is an influence of social rank on the lifetime reproductive success of the sons.



Now high ranking females in red deer do give birth to more sons than daughters. They have a distorted sex ratio at birth. So the question is how do the females do that? Well they can be doing it with sperm selection, if they could detect whether the sperm were X or Y bearing sperm. They could do it with selective abortion, if somehow the conflict between mother and offspring has been resolved in favor of the mother.



Just think about it. There you are, you're an embryonic red deer. You happen to be the wrong sex for this particular mother. She has evolved to get rid of you through abortion, if you're the wrong type. You will try to conceal your sex. You will not be expressing whether you're a male or a female in the surface proteins. So there's a puzzle here. How could selective abortion evolve? Because there is a conflict between parent and offspring about whether you should be able to even detect what sex your child is.



We don't know. What we do know is this: Nutrias do this--nutrias are South-American rodents--and if you have a female nutria who is subordinate or in low physiological condition and she should be making mostly female offspring, but she happens to have a mostly male brood, she just aborts the whole thing and tries again. So that's what she does.



The Seychelles warblers--so a great place to go do fieldwork; the Seychelles are just lovely--there's a warbler that lives in the Seychelles Islands and they control the sex of individual eggs, and they do so--in order to have the correct sex, there is a helper at the nest when they--when the baby grows up they actually have helpers at the nest. So whole families of warblers help to feed the next generation, and what the mother is doing is she's making the right kind of egg for her ecological condition. Sometimes it's helpful to have a lot of daughters and sometimes it's not helpful to have a lot of daughters, and they can control the sex. We don't know how they do it.



So there is definitely sex allocation in red deer and in nutrias and in Seychelles warblers where the sex ratio at birth is being changed in terms of social or ecological circumstances, and it seems to be changed appropriately. Now with chimpanzees--chimpanzees are like us. They have a 50:50 sex ratio at birth, and if you don't have selective abortion, you don't have effective sperm selection, it's hard to avoid a 50:50 sex ratio at birth. So sex chromosomes do that for you.



However, you can still make choices after the baby is born. And this is the inter-birth interval in months, over here, and this line here is for dominant mothers, and this line here is for sub-dominant mothers, and this is about five years and this is about seven years, up here. So it's about a two-year difference.



And if a dominant mother gives birth to a daughter, she weans that daughter, when that daughter's about five years of age. But if she gives birth to a son, she keeps him for two more years. That is a high investment. He's getting more and more expensive to take care of and she's losing time that she could put into another child. But because she's dominant and she's got a son, the argument is she'll get more grandchildren if she invests in him and really makes him into a dominant male. On the other hand--and by the way, this is a highly significant result here; this one is marginally insignificant down here--a sub-dominant mother has a bit more of a tendency to rear her daughters longer and her sons shorter and discard the sons earlier.



Look at what happens to them. This is the survivorship. This is the age of the baby here. This is the son of a dominant mother; so these guys over here. They aren't weaned until they're seven-years-old. As soon as they're weaned, 30% of them die, but the rest of them have extremely good survival, and they in fact do better than anybody else. By age 13 they're just the best survivor class that there is up in this diagram.



Look at the sons of a sub-dominant mother. They're these guys here. They are--this square--they are neglected even before they're weaned. They aren't weaned until five years. So before they're weaned, they're already doing worse, and then once they're weaned they only have a 20% probability of becoming 13-years-old; whereas those of a dominant mother have nearly a 70% probability of becoming 13-years-old. You can see that there are similar effects going on with the daughters. That's a very dramatic pattern.



Now, rearing a son at all, if you're a sub-dominant mother, and you're going to kind of neglect him and get rid of him early, is a very expensive thing. So why is it that they haven't evolved screening mechanisms, at the sperm or the zygote stage, that respond to social rank? We don't know. It would be very adaptive for them to do that.



And I'll now tell you about the German farmers. Klaus Voland, in Germany, has analyzed the demographic data sets of a set of Northwestern German farming communities from the seventeenth and eighteenth century, through the nineteenth century. And during this time there were economic cycles. When times were good, it was possible for a son to inherit a farm. When times were bad, the sons couldn't inherit anything, or only one son could inherit the farm, but in bad times daughters could still marry up.



And what Voland showed is that the probability that a son or a daughter would survive to maturity was dependent upon the economic cycle, pretty much in the same way that we just saw for the chimpanzees. In other words, German farmers invested more in sons when sons could inherit, and they invested more in daughters when daughters could marry up, and the degree of investment was actually reflected in the mortality rates of the children. So it had to do with parental neglect.



So that is one case where it does look like the Trivers-Willard hypothesis actually works in humans. To be fair to the data, I want to mention some of the other cases. There have been large-scale studies in the United States that show that this effect is fairly weak, and there have been some other studies in the United States that show that this effect is fairly strong. So the evidence is mixed on this one.



And I would like to emphasize that in humans it could very well be cultural rather than genetic. After all, people generally do talk about issues like this, and they are understood within families. So it's possible that patterns of parenting could be culturally as well as genetically influenced. However, what one can say is that that's perfectly consistent with the Trivers-Willard hypothesis. It's just that it might have a cultural rather than an evolutionary explanation.



So I think that the Shaw-Mohler theorem is a case in which very disparate kinds of information are being brought together and explained in the same theoretical framework. Remember, we've looked today at sex ratios in mites where you have incest and cannibalism going on. We have looked at sex change in hermaphroditic fish, sequentially hermaphroditic fish, and we have looked at the investment in offspring of the two different sexes in red deer and in chimpanzees; and that's really quite a range of biological information.



If you get into the sex allocation literature, you will find hundreds of more cases where the Shaw-Mohler theorem works. So it indicates that it has captured something that's very important about evolutionary biology. And to remind you of that, it's the fact that in a sexually reproducing population every diploid adult is getting half of its genome from its father and half of its genome from its mother, and the consequence of that is that the male and the female paths to fitness are equivalent. So this is a very fundamental structuring fact about much of the sexual biology of organisms.



In sex allocation we've seen that there are really quite strong connections between mating systems, social structure, sexual selection, population structure, life history evolution and genetic systems. Let me test your understanding of what I've said today about male and female function being equivalent paths to fitness, and about the Shaw-Mohler theorem.



There is a shrimp--and you have all probably eaten it in your dinning halls--which is born male and changes to female. And let us suppose that this shrimp, before there was ever a fishery for it, made the sex change when it was three-years-old. So when it was small it was a male, it changed to a female at three years, and then it lived the rest of its life as a female. Male and female function are equivalent paths to fitness. Now, we create a fishery, and the fishery goes in and it starts catching all those nice big fat females, because they're the biggest ones, and the fishery operates long enough for there to be an evolutionary response. What happens to the age at sex change?



Student: It's longer.



Professor Stephen Stearns: What?



Student: It's longer.



Professor Stephen Stearns: No, they do not spend longer as males. So now you know the answer. But I want to know why. What happens is that they change sex at two-years, rather than at three-years. What's happened is that the fishery has been taking away their female function, and evolution wants them to get half of their fitness through male function and half of it through female function.



In order to maintain that equivalency, it has to create more space in the life through the females. The fishery is taking away space in the life to be female, and so the sex ratio, the sex change shifts to an earlier point. This is exactly what's happened, and if you buy fish at A1 Fish Market, or you have them in the dining hall, you will get shrimp in those fish markets that do this, and they have responded to the human selection pressure created by the fishery, and it's changed the age and size at which they change sex.



This is actually one of the reasons why this course is called Principles of Evolution, Ecology and Behavior. It's because there are examples like this where it doesn't make any sense to separate these fields. All of this stuff is going on, in these examples. You have dominant behavior, you have ecology, population density and evolution all interacting with each other. Okay, so next time sexual selection.



[end of transcript]

Sexual selection is a component of natural selection in which mating success is traded for survival. Natural selection is not necessarily survival of the fittest, but reproduction of the fittest. Sexual dimorphism is a product of sexual selection. In intersexual selection, a sex chooses a mate. In intrasexual selection, individuals of one sex compete among themselves for access to mates. Often honest, costly signals are used to help the sex that chooses make decisions.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 11

Transcript



February 11, 2009



Professor Stephen Stearns: Okay. Tomorrow is Darwin's birthday. It's 200 years since he was born, on the same day as Abraham Lincoln. Astrologers have made a lot of the fact that both men were deeply opposed to slavery. But today we're going to talk about sexual selection. So this is a Valentine's Day lecture. [Laughter]



Sexual selection is actually a component of natural selection. When Darwin looked at the extravagant plumage of the birds that you just saw, he thought there has got to be something special going on here. [Crew talk] When he saw all of these extravagant behaviors, he thought there must be something else going on, besides natural selection, and that's because Darwin thought that natural selection, in some sense, was the survival of the fittest.



We now know that natural selection really is the survival of those that reproduce the best, and that sexual selection is a component of natural selection that is associated with mating success. So basically sexual selection is a case in which mating success is trading off with survival.



And to bring this home to you, as you sit here in your 18 to 45-year-old state--there are various ages in the audience--I'd like you to consider the fact that the ratio of male to female mortality, in the United States, starts to diverge early in life, and by the time one has hit late teenage and early twenties, the ratio of male to female mortality is climbing rather strikingly. This is from all causes; this is from external causes; this is from internal causes. And actually this divergence here is enough to account for the different life spans of human males and females, which differ by about four or five years.



Now that is sexual dimorphism, and sexual dimorphism in mortality rates, and it appears to be associated with blockheaded risk-taking behavior. It appears that males behave differently at those ages than females do. Now we don't know whether that's evolved and genetic, or whether it's culturally influenced, but I invite you to consider those alternative possibilities and think how one might test them.



From animal studies, we know that the more polygynous the species, the greater the difference in male and female lifespan. There isn't any difference in monogamous species. So if you look at swans or other monogamous birds, the males and the females live the same amount of time, but the more polygamous a species is, the shorter the male's lifespan relative to the female's.



So how does sexual selection work? It might account for that pattern. How does it work? Well if a change in a trait is going to increase lifetime reproductive success, by improving the ability of an individual to attract or to control a mate, or to achieve fertilization, it can be favored by selection, even if it lowers survival probability. This is a Woody Allen film about sex and death.



Now sexual selection will change traits that influence mating success until the improvement in mating success is balanced by costs in other fitness components; then the response will stop. This will not go on to the point where there's wholesale slaughter and suicide. Although in some few cases there is sexual cannibalism during copulation--in the Australian Redback Spider-- and the male does appear to insist on committing suicide. So that would be probably the most extreme case. But that's not normal, that's really an extreme case.



The normal case is that if there is sexual selection going on, then the sexes will diverge in their behavior and their morphology, and their traits and their behavior will be modified in ways so that they are getting better mating success, but they are incurring costs, in terms of survival.



Now this line of thought explains why organisms will take risks to mate--and often they will take extreme risks to mate-- and it explains why juveniles develop secondary sexual characters only on maturation. That's because the secondary sexual characters, which are the things that we think of as causing the two sexes to look different in any species, bear with them costs, and those costs can be imposed from a variety of sources. The costs may be that if you look like an adult, you're going to elicit competitive behavior from other adults--you might get beaten up--or it may that it simply makes it much more difficult for you to escape a predator. So the costs can come in from all sorts of places.



The main questions about sexual selection are how did it originate? And we are now pretty well satisfied that before there was anisogamy, there could not be any sexual selection. There had to be gametes of different sizes, and there had to be individuals specialized on producing small ones and big ones before you could start getting things that functioned as males and females, and then evolve to begin to look like and behave like males and females.



The mechanisms of sexual selection are basically two: competing for mates and choosing mates. So there's force and subtlety involved in this process. There's a lot of evidence for it. This is, as you might imagine, since we are among the more sexual primates--we're not quite as sexual as bonobos, but we are a relatively highly sexed primate--it's not unusual that this is an area of biology that has attracted an awful lot of attention. You can find thousands of papers on sexual selection.



The strength of sexual selection is actually on the day of mating determined by the operational sex ratio; that is, the local ratio of males that are ready to mate with females who are ready to mate. Okay? So that's just a brief outline of some of the main points.



Now about competing and choosing. Competing and choosing have different consequences. It is the limiting sex that can be choosey--okay?--and normally individuals of the other sex compete. Now it is quite possible that if one sex is limiting, and the other sex is competing for the attentions of that sex, that the individuals among the limited sex can actually compete with each other for the attentions of the suitors. There's nothing ruling that out. It's just that I'm describing here the processes and forces that are stronger in the two sexes. That doesn't mean that other things aren't going on; there's arguably a lot going on.



Generally speaking, mate competition will be stronger in the sex that has the greater reproductive potential, and it's the one that should be competing for the sex with the lesser reproductive potential. And usually males have greater reproductive potential, females have lesser reproductive potential; so males compete and females choose, generally speaking. You'll see that there are interesting exceptions.



Now, what should a female choose? I'll already tell you this is a big topic in evolutionary psychology. David Buss, at the University of Texas, wrote a big review paper on this a few years ago. It's highly controversial. It's fun to read this stuff. It's difficult to come to a hard science conclusion on it. Basically what Buss says is that males choose young females that look healthy and have high reproductive potential, and females choose males that have access to resources and are likely to contribute to child rearing. Okay? And he says this is cross-cultural; all cultures, all times, that's what people do. Obviously that could be controversial, and there are a lot of refinements on that picture, and there's a lot of evidence that could be better. But that's what Buss claims. That's for humans.



What about animals, where you can actually do experiments and do manipulations and ask them to tell you why they are choosing mates? Well here are some hypotheses. A female could look at a male and say, "Does he control important resources? Will that one be a good parent? Will it supply food efficiently?" Or, looking at it, "Is that potential mate healthy? Is it free of parasites, and is it advertising its ability to resist parasites and pathogens with a costly signal that gives me an indication that in fact that thing is honest and is not trying to deceive me?" Or, "Does that potential mate have traits that are attractive to sexual partners? Will I have a sexy son?"



Now this sets off a very interesting co-evolutionary process between the preference genes that are sitting there being expressed in the female's brain and the expression of that in the form of some kind of sexy morphological trait in the male's morphology. And these genes for preference and genes for attraction come together in the offspring, and that has very interesting consequences.



Well what do we know about this? André Dhondt and his students, who at that time were in Belgium--and André is now at Cornell--did an interesting study on Blue Tits. Now the point about Blue Tits, that makes them useful for this, is that they frequently have extra-pair copulations. That means that Blue Tits indulge in adultery a lot.



And because of genetic fingerprinting, you can go out and you can determine the paternity of offspring in this brood, where the male is having his primary residence, and in neighboring broods, and when the male flies out, perhaps to have an extra-pair copulation with a female in a neighboring territory, another male might fly in and have an extra-pair copulation with his female. And you can trace the consequences of this. Okay?



We define as unattractive guys that don't get much action, and we define as attractive guys that get a lot of action. Okay? So that's an operational definition of attractive. And if the unattractive males turned out to be smaller and they died younger than attractive males--so female Blue Tits are able to pick up on something about the physical health of the males that they're looking at--the offspring of attractive males, in their own home brood, in their own home nest, lived longer than the offspring of unattractive females.



Now you could explain that by direct benefit rather than by females looking at some signal in the male's morphology or behavior that he had especially good genes, if the attractive males had better territories and were better parents. That we don't know a lot about. If the extra-pair offspring of the attractive males--so the babies that were laid in other nests, in other territories and were reared by other people; so they were foster-children in other territories--if they also had better survival, that would be hard to explain in terms of direct phenotypic reward, and would then indicate good genes.



So this is an example to show you how you can apply natural experiments, in the field, to try to settle the question of which hypothesis for sexual selection is correct--is it good genes, is it direct benefits?--and show you that some of the evidence had been collected by I think--2002, I think, is about when this came out. There may be more out there now and you can go find out. At any rate, this is something that can be done now with DNA fingerprinting and with small birds.



There is a sexual selection maxim, which is kind of a default condition, and that is eggs are expensive and sperm are cheap, so females are limiting and are going to be choosey, and males have potentially higher reproductive success over a lifetime than a female, but probably also higher variance in reproductive success. And the consequence of this is that the lifetime reproductive success of the females is basically limited by the number of offspring they can produce; the lifetime reproductive success of males, by the number of females they can fertilize. That's really asymmetrical.



That means that in this default condition the females become a limiting resource, and that sets off competition among males for mates. It allows females to choose partners. And so usually females are choosier than males, and males are more promiscuous than females. But there are a lot of exceptions. Right at the end I'll show you a couple of very beautiful polyandrous birds where females hold harems of males, and their morphology has been changed so that in those species of birds they are the bright, dominant, colorful ones, that look like males. So this is a general principle, and you should note that sometimes sperm are actually more expensive than eggs; it's not always true that sperm are cheap. Here's a case.



This is a case in which the sex that is choosey changes in a plastic fashion as a function of how much food they have, and that's because in Katydids males contribute nourishment to the females in their spermatophores. So a female is not only getting sperm from a male, she's getting food from the male. Okay? Now if food is scarce, then female Katydids are actually reproductively limited by how many male spermatophores they can get. And at that point males back off, they don't court so much, they get to be kind of coy, and the females fight over the males and the males become choosey.



However, when the food is abundant, the males are reproductively limited by the availability of females; females are getting a lot of food from sources other than spermatophores; males court and females are choosey. And you can take these and you can just flip them back and forth, from one mode to the other, just by how much you feed them. So that's actually a nice test case, because here you're taking the same individual organisms and changing them with an experimental manipulation between two different courtship modes; and it gets directly at this idea.



Now, what about competition for mates? There is a lot of armament out there in Nature. You've seen some of it. You've seen the antlers on deer. You've seen the tusks on narwhales. You've seen the tusks on elephants. You've seen that a male silverback gorilla weighs 450 pounds, and a female gorilla weighs about 120. There are major differences in body size of males and females in many species.



So these are set off--the evolution of that difference in body size is really driven by contests, scrambles and rivalries. And during these contests females can be sitting there, looking at the males go at it, fighting for access to them, and they could be choosing males for their competitive ability. So the fact that the males are fighting isn't ruling out female choice, it's making possible perhaps another kind of female choice. That does explain large, well-armed males, and the most striking examples of this dimorphism are in pinnipeds.



So here are two southern male elephant seals, okay? Bull elephant seals. By the way, these guys are very superior divers. They will go out offshore, oh 100 miles or so, and dive down to a depth of oh between 1000 and 3000 feet, to fish for squid, and they're very good at it; they're kind of like little mini whales cruising around out there. And a male elephant seal will spend about nine months a year storing up a lot of food, because then he's going to haul up on a beach and try to protect a harem on the beach, and try to chase off other males and fight vigorously. And during that three months he doesn't eat. He gets extremely grouchy.



Now it is possible for these guys to control a harem of about forty or fifty female seals on the beach. And it's not easy to run down a beach if you're a 4000 pound male elephant seal. You are built for swimming sleekly through the water, chasing squid, not for humping along the beach with your four flippers. Okay? But these guys do, for three months, and they get all beaten up, chasing off juvenile males that are coming in and trying to sneak copulations with their harems.



And, because of this spatial situation, if you're a juvenile male, you can actually give the females a little chance to make another choice. So the juvenile males hang out sort of on the boundaries between the harems of the big dominant males, and try to sneak copulations. This sets off a situation of controlled chaos that goes on for three months, and everybody gets exhausted fighting.



If you look at the ratio of male body length to female body length, and look at the harem size that a pinniped can control--what you have here is data on different pinniped species. This, I think, is a harbor seal, which is virtually monogamous; so harbor seals tend to mate for life. But an elephant seal will be about 1.6 times as long as a female, and that means it's how much heavier than a female? What do you do with that 1.6 to estimate the difference in weight? Can't hear you.



Student: Cube it.



Professor Stephen Stearns: You cube it. That's right. So that means that the male elephant seal is on the order of five or six times heavier than the female. So if he's 4000 pounds, she's about 850 pounds, something like that.



And that's a pretty strong relationship in biology, for sexual dimorphism versus harem size, and that illustrates the importance of competition for mates in controlling the evolution of size differences between males and females.



Now the one that's probably a bit more fun is mate choice. I had a graduate student in Switzerland who went to a behavioral ecology meeting in Sweden, at a time when mate choice was a hot topic in the literature. And it is a standard feature of scientific meetings that in the evening there's a bar, and people are talking at the bar, and so she quietly went around and decorated males with various things, like feathers or whatnot, and then stood back and took notes to see how long they got to chat up a woman, depending upon what kind of decoration they were wearing. And she showed a very significant effect, and the ones that looked weirdest actually got the most attention. [Laughter] So, just a tip. Okay? [Laughter]



Now if you're really choosey and you're able to detect high quality territories or good genes or sexy sons or something like that, you can improve your fitness by being choosey. But remember to be choosey you have to take time. Choosiness is essentially shopping. Right? Shopping takes time. If you shop too long, you may miss the opportunity because the shelf will be empty. Okay?



So organisms should be careful, but not too careful. There's kind of an optimal waiting time, and after awhile, as the season progresses, for a seasonally breeding organism, there's going to come a time when mating with anybody is better than not mating at all. So this business of being choosey is constrained by time.



Now choice based on an immediate phenotypic benefit--that means I'm going to choose this mate because he's got a great territory and I'm going to get a lot of food, or I can see that my babies will have a lot of food; that would be an immediate phenotypic benefit--that can explain a lot, but it won't explain extravagant male morphology or leks, and very often extravagant male morphology and leks are associated with each other.



You just saw some in the video at the beginning. That Bird of Paradise was on a lek, and I'll show you some more in a minute. So things that lek are peacocks, sage-grouse, Birds of Paradise. And a lek--it's one of the few Swedish words which has been appropriated into English. Lek in Swedish means--has two meanings. Meaning number one is a sports place. So you can actually drive down a road in Sweden and see a little sign that says Lek, and you'll see a sports field. But it also means the same thing that it does in behavioral ecology in English, which is a traditional display ground where males come year after year to advertise and try to attract females to mate with them. Okay?



And this is a mating system in which the males are then not going to go off and take care of the babies. The males sit there and display and fight with each other. Females come and mate with them, and the only thing that the female gets from the male is genes. These are some things that lek. This is a sage-grouse at Malheur National Wildlife Refuge in Oregon. This is a Bird of Paradise and this is a peacock. Now these males--these are all males--have pretty extravagant morphology, but they not only have extravagant morphology, they have extravagant behavior.



You saw what that Rifle Bird was doing, waving its wings back and forth. Anytime you see something like this, you can bet that if you were out there and you saw it in action that there would be feathers in motion; there would be dances going on; there would be really elaborate stuff that these birds were doing with their behavior to attract mates.



For example, the male sage-grouse in Malheur in Oregon go to the lek in January. In January, in Eastern Oregon, the temperature can be 20 degrees below 0. There's snow on the ground. These guys are getting up in the dark, before sunrise, to get out there on the lek, to try to get a one-up on the competition. They puff up their breasts and they make a popping sound when they do so, and then after they pop they coo. So they go pop-pop, coo, coo, pop-pop, coo. You can hear them a kilometer away. And they make themselves as visible as possible.



Around the lek there are lurking coyotes. Overhead, cruising through the air, there are Golden Eagles. These guys are taking major risks to get up at five in the morning to go out and try to make love in the snow. You know? [Laughter] That's a serious modification of male behavior. Talk about being a prisoner of your hormones. These guys are in jail. [Laughs]



So what kind of an experiment could you do in the field to try to decide what's a female looking for? Well Malte Andersson had a great idea. He wanted to work on the African Widowbird. African Widowbirds have--the males have naturally long tails, and they control territories within which two, three, four, five females might nest.



So what Malte did--by the way, he did this in Masai Mara, in Kenya--he shortened tails on some Widowbirds by simply cutting them off with scissors. On his control group he cut the tail off and glued it back together, so it didn't change in length. And then on his experimental group he cut the tail off--he took the cut tails from the short-tailed ones and glued them on to make super long tails. Okay? So he had three groups. He had short-tailed controls and real long tails.



Now the ones with shortened tails only averaged half a nest on their territory, and the ones with the lengthened tails averaged nearly two nests on their territory. Individuals were assigned at random to these different groups. And so the data indicate that female Widowbirds were building nests on territories of males with longer tails. And then the question is, if that's such a great thing, if you're going to double your reproductive success with a longer tail, then why don't you already have it? Darn it, why hasn't evolution done that to you?



Well the answer is probably that natural selection is preventing a further increase in male tail length because females are preferring much longer tails than are found in natural populations. It's fun to give this part of the lecture in German, because those of you who know German know the double meaning of Schwanz in German; it's what you imagine.



Okay, there's another hypothesis, and that is what is a female looking for? Well she's looking for an indication of good genes, under this hypothesis, and that would mean that a female should prefer a male displaying an honest costly signal--notice here I've put honest and costly together--an honest costly signal that they contain genes for superior survival ability; for example, genes for parasite and pathogen resistance, even for different MHC alleles.



Now the vertebrate immune system is partially integrated into the vertebrate nervous system. The two systems can send each other information. If there was a way that your sensory system could pick up information on the composition of the MHC alleles, in a potential partner, and send it to your brain, that would affect your mate choice.



This leads into something that you may enjoy looking at. If you're into ISI Web of Science, type in T-shirt Experiment, and look at the impact of body odor on how attractive a potential mate smells. Okay? It turns out that if you do that, and then you do the DNA sequencing to see whether or not the people who are reporting attractive or unattractive have similar or dissimilar MHC alleles, the ones that are reporting that a smell is attractive are the ones who have different immune genes, and the ones who are reporting that a smell is repugnant have similar immune genes.



And the way the immune system works in the offspring, to resist infectious disease, is by generating diversity within the body, and it can only do that if the genes are different. So you have to find a mate with different MHC alleles if you want to have disease resistant offspring. And there is some evidence in humans that in fact we do react to scent and that there is information in scent. By the way, this is well established again--it's not so well established in humans because we can't do manipulation experiments--but it is well established in mice, that mice do this.



And where people make mistakes and they do mate with people who have similar MHC genes, they get into a situation where there are multiple spontaneous abortions. So it appears not only that there is a level of selection at mate choice, but there is also a level of rejection of zygotes that are potentially not going to resist infectious disease. That's work by Carole Ober at the University of Chicago, working on Hutterites. So interesting stuff here.



Now what kind of evidence have we got? Well if a male produced an ornament in order to advertise that he was resistant to disease, then you would expect that male fitness would decrease with increased parasite infection. So that would be an assumption behind it; that would be the selection that was driving it. The condition of his ornaments should decrease with increased parasite burden. So the less he was able to resist the parasites, the less dramatic an ornament he would be able to express. So that means that that ornament's got to be costly.



Then there must be some heritable variation in resistance, or there wouldn't be any response to selection; just go back to the first basic four conditions for selection: that must be there. And if this holds, then females should be choosing the most ornamented and the least parasitized males. And there are three cases that are pretty well worked out where that's exactly what appears to be going on.



So what female guppies appear to be looking for are orange spots in their males. What female pheasants appear to be looking for are red irises around the eyes of the males. And what female barn swallows appear to be looking for are nice long symmetric tails; they like the symmetry of the male's tail.



Now that would be a good genes argument. The male's got a gene for parasite resistance, so I'm going to make with him. That's a good gene. And that is where the Fisherian process of sexy sons would start. Okay? So I'm now shifting into the argument for the third hypothesis, which is you choose a male because you think that if you have a son by him, that son will get a lot of matings.



So preference for good genes will select for the preference itself, and that makes the preferred trait an object of selection, and it explains the evolution of ornamentation. You can see it like this. Suppose the reason a female guppy likes a male with an orange spot is that the only way he can make that orange spot is if he gets carotenoids out of the crustacea that he eats. So if he's really good at finding high quality food, he can make a bigger orange spot. So it's advertising his foraging ability. Okay? That's a good thing.



So that gene for foraging ability comes together in the offspring with the gene for the preference, and because the male has better foraging ability, the gene for the preference will hitchhike on the reproductive success of the gene for the foraging ability, and females will develop stronger and stronger preferences for a male with orange spots. So that's how the process gets going, at the beginning. It's thought that initially the preference develops because it's a preference for a gene that actually affects reproductive success in your offspring.



What if now that guppy population moves into a new habitat that doesn't have any crustacean in it, and it becomes difficult perhaps for the males to make carotenoids? But they still can, they can still make orange spots. But the females have the preference. The male is no longer giving off a signal that's reliable in terms of good genes. All he is signaling is that he's attractive to females.



Well now evolution has a new reason to maintain that selection. It's a selection simply for the attractiveness of the offspring, because a component of reproductive success is mating success, and by choosing a male that has an orange spot, the female is also choosing mating success in her sons.



So that leads to runaway selection for sexy sons. So females are preferring males with higher fitness. Their preference genes get united in their offspring, with the male's genes for higher fitness. The female preference genes then hitchhike on the male's fitness genes. Once their preferences are established, they work on male traits that are otherwise neutral, or maybe even disadvantageous, except that they are preferred by females. So they lead to success in mating. So then, if all that happens, then mothers will gain in fitness by selecting fathers with heritable traits that make their sons attractive to females in the next generation.



In the threespine stickleback, the intensity of the son's red coloration is correlated with the daughter's preference for red. So what I've just told you about the genes for preference and the genes for the male trait coming together in the offspring happens to be true, in sticklebacks. But when you then ask, "What's the deal with red color on the belly of the male stickleback?", you discover that it's not only genetically correlated with female preference; bright red males resist parasites. So by choosing them, females are avoiding parasitized males, and that's also satisfying a good genes hypothesis.



So you can see that in this case, the data in fact do not distinguish between the two. It's not like it's either/or. It looks like, hey, both things are going on at the same time. Females are choosing sexy sons who are also parasite resistant.



Now there's a third possibility, and that is let's suppose this kind of thing has been going on in the past and females have developed certain sensory abilities, to perceive the potential mates. You guys are not particularly good at perceiving potential mates in the ultraviolet. Okay? Bees are, but you're not. So your sensory capacity is limited to certain windows, both with your eyes and your ears and your taste buds and everything else. And the idea is that the sensory capacity inherited from ancestors would bias the traits. Females might just be selecting males they can see or hear especially well.



So one well worked out example is that the female eardrum in a Tungara frog is tuned to receive some frequencies better than others. Here is a male Tungara frog in Panama calling, and his call signal is being picked up by the ear of the female, and he can't change his call signal out of the frequency range that that female ear can hear. If she is attracted to him, he has reproductive success. But unfortunately, that's a perfectly fine frequency for a bat to hear. And in fact a fringe-lipped bat is a frog eating bat, and it does exceptionally well during frog breeding season by swooping in and munching up the males who are dutifully calling to try to attract their females.



Now the idea here is that the male can't evolve out of a frequency range that the bat can hear because the female's eardrum is constrained to be a certain size; that's the sensory bias hypothesis. Now, so I've stepped through the main hypotheses that are thought to drive female choice. So female choice could simply be for things that she can hear or see particularly well, as well as for sexy sons or direct benefits or good genes.



Now what is the actual context in which this is going on? Well it's when mating is happening, when choice is being made. And that's where the operational sex ratio comes into play. It basically is determining the opportunity for selection, and it varies with mating system and parental care. So sexual selection, which produces striking differences in the behavior and morphology of males and females, is correlated in ecology and evolution with mating systems and patterns of parental care. These things all go along with each other to form syndromes of traits.



In monogamy, equal numbers of males and females have offspring, and each sex has one partner, and there's not very much difference in the operational sex ratio and not much opportunity for sexual selection. In polyandry there are more males than females, that have offspring, and each female has two or more male partners. So there is great variance in reproductive success among females; there's less variance in reproductive success among males. In the reverse pattern, in polygyny, more females than males have offspring, and each male has two or more female partners; that leads to harems and leks. And then there are things like polygynandry where each sex may have several partners.



There's a little brown bird, an LBB, called the Dunnock. It looks a little bit like a hedge sparrow. It lives, among other places, in the botanical garden at Cambridge University in England, where Nick Davies has studied it for a long time, and it had the notoriety of being regarded as an exemplar of marital fidelity, until Nick studied it. And once Nick got in there with his DNA fingerprinting and did paternity analysis, he discovered that Dunnocks are polygynandous. So each sex is mating with several partners. A female sitting on a nest will have eggs in it that were inseminated by several males, and the father who's bringing food to that nest has his genes in eggs that are in several other nests. So that's polygynandry, and well exemplified in the Dunnock.



Now the effects of mate choice are thought to be especially strong in these two circumstances here. That's where one sex has relatively little variance in reproductive success; the other has large variance in reproductive success. One sex is limiting; the other sex is competing. One sex is choosey; the other sex is fighting.



I told you that I would show you some polyandrous birds. This is a Wattled Jacana, and the Jacanas--we ran into them on the Amazon--a Jacana female will hold a territory within which three, four or five males will build nests, and she will go around and lay--they'll fertilize her and she'll lay eggs into each of their nests. But she doesn't spend any time raising the babies, she just fights off the females on the neighboring territories. So males take care of the babies and mom fights for the territory; and that happens in the Wattled Jacana.



This is a Phalarope; this is a female Phalarope. They are basically related to the Sandpipers; so they're shore birds. They live in the far Arctic. And a similar pattern. The male sits on the eggs. A female holds a territory within which three, four, five males have nests. And there've been some very interesting studies done on the mating physiology of Phalaropes.



When a female Phalarope is displaying, in her courtship display, and attracting males, her ovaries are expressing testosterone. You could imagine that the courtship display of the female Phalarope had evolved in an ancestral male, and that all of the control machinery for that was all set up, and all you had to do to get it expressed in the other sex was turn on the testosterone at the right time; which is what her ovaries do when she's displaying.



When she then goes over to the nest to lay the eggs, her ovaries secrete estrogen, and she--her physiology is switching back and forth between a male display in competitive cycle, driven by testosterone, and a female lay egg and make yolk and lay egg cycle, which is controlled by estrogen.



So these sorts of secondary sexual traits are not only associated with mating systems and patterns of parental care, they also set off a cascade of physiological integration throughout the organism, and uncovering that leads one into a whole host of interesting physiological questions.



So to summarize sexual selection. It's a component of natural selection in which mating success trades off with survival. It's not a separate kind of selection, it's part of natural selection. It accounts for many of the attractive ornaments of plants and animals. It raises the interesting issue of aesthetics and why our brains see things as beautiful that other things find attractive.



There is contest competition for mates which are the scarcer reproductive resource, and that will explain a lot of sexual size dimorphism--bull elephant seals, things like that--particularly in polygenous species. We've seen there that the degree of dimorphism is directly related to the degree of polygamy; the bigger the harem, the bigger the size dimorphism. There has been a lot of documentation actually of active choice of the non-limiting sex sometimes. So that's going on.



And whether or not this indirect mechanism--this Fisherian runaway process, that leads to preference for sexy sons--whether that is really needed to explain ornaments in lekking species, it seems to be logically the only possible explanation left standing. It's as though you have ruled--you're Sherlock Holmes and you've ruled out all of the other hypotheses. But getting positive evidence for that has been difficult. Okay?



So this looks plausible. I think it's likely, but at this point the positive evidence indicating that that has been under selection is still out there. Getting whole genomes of some of these organisms might solve it, because you can then look for signatures of selection, if you can identify the preference genes; that's a long-term project.



So let's go back to this. I'd like to leave you with this. This is you guys. Here you are; you're probably somewhere around this age group. And the mortality rates of the males in the audience, on average--every insurance company in the country knows this; every time you apply for car insurance this difference manifests itself in your monthly bill--the mortality rates for male humans at this age are several times those of female humans, and they appear to be taking risks. So I'll leave you with the unanswered question of whether that's a product of sexual selection or not. And next time we will talk about speciation.



[end of transcript]

Speciation is the process through which species diverge from each other and/or from a common ancestor. There are several definitions of species, most of which focus on reproductive isolation and/or phylogenetic similarities. This can cause some controversy. Speciation can result from geographical separation or ecological specialization. There are stages of speciation in which organisms cluster first into distinct populations before finally becoming different species.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 12

Transcript



February 13, 2009



Professor Stephen Stearns: Okay, today I have put up a slide from the first lecture, just as a signpost and landmark to make sure that you're oriented on the path through the course. Basically the material we cover before Spring Break is organized into these large sections, and today we're making the transition from microevolution to macroevolution. And you'll recall that in microevolution we had six lectures on microevolutionary principles, and then we had five lectures, that we just completed last time, on how phenotypes, organisms, how they're designed for reproductive success. We're now going to make the transition into macroevolutionary principles, with the process that connects microevolution to macroevolution, and that is speciation.



So as we now move into macroevolution, today's talk is really mostly about speciation. Then we will, next time, have a talk about phylogenetics and systematics, and then about how you can use the combination of these principles to look at evolutionary trees and to place them on maps, and then to place the evolution of traits onto trees and onto maps, so that you can integrate space and time, and history.



Then we have three ways of looking at the history of life. The first is more abstract, I think a little bit deeper, and that has to do with key events in evolution: origin of life, multi-cellularity, language, things like that. We'll have a review of major events in the geological theater. For those of you that like firecrackers on the Fourth of July that's fun, because that's where we have meteorite impacts and extinctions and stuff like that. And then we'll take a look at the fossil record and what it- the kinds of unique insights that you can get out of fossils that you really can't get out of just looking at living organisms. So those are three different ways to approach the issue of the history of life.



Okay, today speciation. I would hope that by the end of today's lecture and the end of your reading and discussion in section about this, that you would be able to deal with this set of issues. What is a species? How do they originate? What kinds of experimental evidence or observational evidence do we have to back up the claims about how they originate? What's going on during speciation, from the point of view of genetics; if we track the genes through the process of speciation, what do we see? And then there are some special issues: asexual species and cryptic species.



I would like to signal that this is a part of biology in which some of your teaching fellows have special expertise. So if you would like to get to the cutting edge of phylogenetic research, you have got some people in section who can help you, and this department happens to be particularly good at that. There was a front page report in the New York- well on the Science Page of the New York Times, in their Darwin Section, they were reporting on Stephen Smith's Ph.D. thesis. He just got his degree here last year. But he assembled the largest Tree of Life for the plants. So we've got people like that running around, and you ought to tap into them, if you feel the urge. Okay?



Now here is a basic observation, and it is one of those things that just seems so natural to us that it doesn't occur at first sight to ask how it might be that way. But in fact it is a puzzle. We have wild diversity in the world. Please forgive me botanists. I had some help assembling this slide. I would like to have had a few more neat plants in there; there are some incredibly neat plants that could go in there. But if we just look at the world, it's amazingly diverse. Okay? So we look out there and there's lots of different kinds of organisms, and they seem to be in discrete groups, separated from other such groups, and in many ways: appearance, behavior, ecology, genetics.



So why is the world like this? How did that come about? Why is the planet not simply covered with a homogenous layer of primordial slime, rather than these different things? For a long time it wasn't that way really. The prokaryotic world was genetically diverse, but it certainly didn't have this kind of morphological diversity in it. Well those things that are separated are called species, and this is the guy who profoundly influenced this kind of biology.



His name's Ernst Mayr. Ernst died a few years ago at the age of 100-and-something. So he managed to keep active for a very long time. I knew him. He was an impressive guy and he had an almost unprecedented ability to claim that he had already said it.



Now his definition of what a species is--this is from a version of a book that he wrote in 1963, but he had been working on this idea from about 1942, and his idea was that a species is a group of actually or potentially inter-breeding natural populations that are reproductively isolated from other such groups. So it's the capacity for reproducing together that unites the members of a species, and it's the inability or the lack of opportunity to reproduce with individuals of other populations that marks the separation between species; according to Mayr.



Now there were very good reasons for this definition, and it really captures the essence of genetic separation. But there are cases where it doesn't apply. As a matter of fact, I think that biology has a profound capacity to erode the categories invented by humans. [Chuckles]



There are almost always exceptions. To that, I would like to add that Ernst Mayr was a great ornithologist, and that the kinds of patterns you see in species, in birds, were what motivated him to come up with this definition, and if he had been a plant biologist he probably wouldn't have defined things this way. Okay?



Now just something to think about. Does everything really have to belong to a species? Would there be some itch that you needed to be scratched if not everything belonged to a species? Would that make you unhappy for some reason? I'm going to let that one hang in the air.



Okay, now when we look out there and we see that things are separated, there are some pretty straightforward mechanisms that actually separate things, and so this is part of the vocabulary building exercise for speciation science; and it's also a little bit of biology. There are isolating mechanisms that are common, they fall into three categories, and they look a little different in plants and animals.



The first category is pre-mating or pre-zygotic isolation, and in plants that's often determined--not always but often--by pollinator behavior and flowering times, and in animals it is determined by mating behavior and gamete release. So here we have actually a place where sexual selection, from the last lecture, connects into speciation, because who you choose as your mate is going to determine whether there's an opportunity for inter-specific hybridization or not.



So this is actually an issue about mate choice, which is kind of at a higher hierarchical level than the issue of should I choose my mate for resources or good genes or sexy sons or something like that? Should I choose a mate, because in mating with that individual I will form hybrids or I will form members of my own species? In a minute you'll see some pollinator behavior slides; so just to anticipate that.



It is quite possible for plants to be separated just by flowering time. Imagine a valley that's running east-west, in a temperate area of the planet, and it is getting sun earlier on one slope than on the other, simply because of the angle of the sun to the earth. Everything's going to speed up on the warm slope and slow down on the cold slope, and you're going to get different flowering times for purely biophysical reasons, on the two slopes. So initially a plant population might come in after maybe the glacier has melted off and colonize those two slopes, and they wouldn't be able to avoid having different flowering times, and therefore starting to separate genetically on the two slopes. So there are all kinds of reasons for separation to start.



Now the second class of isolating mechanisms occurs a bit later; it's post-pollination or after insemination. And in plants there are--and actually in many algae and ciliates--there are self-incompatibility mechanisms. These are actually put in place through recognition molecules. And there is an interesting--gamete biology is very interesting. There's a lot of mate choice which is going on at the level of the sperm finding the egg and the egg sitting there and deciding, "Do I want this one or not?" Throw that one away and take another one. And these are mediated by well understood enzymatic reactions and protein structures; bindin and lysine. The self-incompatibility argument in plants basically has to do with the costs of inbreeding, and the costs of selfing.



And the arena in which that takes place is after the pollen grain lands on the style of the flower and starts to grow down the style, towards the ovary of the flower, the tissues that are in the style are checking out that particular pollen grain, which is making basically a little plant-like thing, as it grows down towards the eggs, and that is where the self-recognition is implemented. If its pollen is coming from that same plant, it'll get killed at that point.



So there are post-pollination and post-insemination mechanisms of isolation. Now after fertilization occurs, post-zygotic isolating mechanisms basically have to do with viability, survival and fertility. So hybrid inviability or infertility is a common thing, once two species have diverged to a certain extent.



And of course the commonest one that you're probably all familiar with is the mule; the mule is a cross between a donkey and a horse, and mules are sterile. So hybridization between donkeys and horses isn't going to go anywhere evolutionarily because there are never any grandchildren. I believe the same is true for ligers, crosses between lions and tigers. I'm getting nods from the zoological aficionados in the audience. So thank you for the confirmation. [In fact female ligers do breed successfully with male lions. Male ligers are sterile.]



However, at this stage, often fairly distantly related plants are able to hybridize. It's usually not across the boundaries of genera or families, but sometimes you can get plants from two genera hybridizing with each other, which may be an indication that the classification has been wrong. But plants generally hybridize a lot more easily than animals do, and it may have something to do with the differences in their developmental complexity. Usually the reasons for hybrid inviability in animals are developmental abnormalities.



Okay, so I had signaled that we were going to look at a pre-zygotic example. So here is species separation by pollinator recognition. Here are two columbine species, and they can overlap geographically. You'll notice that they really have very different colors, and that is actually related to the brains of the things that pollinate them. Yes, moths do have brains. Okay? So hummingbirds are notorious among pollination biologists for loving red and yellow, and if you see a white flower, you can normally--it's a pretty good bet that it's going to be pollinated by a moth or a bat.



And in fact if you were to look at these things in the ultraviolet, you would probably see that there were, in the ultraviolet, interesting markings on them, and often flowers that have ultraviolet markings on them are bee pollinated, because bees see particularly well in the ultraviolet. So these are two species that are separated by pollinator behavior, and I invite you to play through a scenario in your mind of how their ancestor had the same color and then how they might have gotten different. Okay? It would've been a gradual step-wise process, as they specialized on a particular pollinator.



Okay, so species can be separated by various mechanisms and at various stages in the process of reproduction. Mayr gave us a biological species concept; that's the biological species concept, isolation. And there are plenty of others now. And I've put this list up here, not for you to memorize, but more or less--I do invite you to go through and sample these species concepts--but to show you that actually to try to state logically what we mean when we say the word species has been a difficult task for phylogenetic biologists to deal with, and the fact that I can put a list like this up there is a measure of the difficulty, and a measure of the controversy and the disagreement that has occurred over this issue.



What each of these definitions does is try to define a species from a slightly different biological starting point. And what they're trying to do essentially is get the most general and useful definition that they can. And in some way they all fail, which is kind of neat, because it means there's still work to be done, but in some way they're also all partially correct.



So I told you about Mayr's concept. The recognition concept basically is based on mating systems. So species are things that will decide to mate with each other; that's Hugh Patterson's. The phylogenetic species concept--there are various ways of looking at the Tree of Life and deciding what on it constitutes a species. So Joel Cracraft said it's a cluster or organisms that are distinct from other such clusters, within which there's a pattern of ancestry or descent. So he says well essentially it's the stuff that's out there at the tip, that's closely associated.



Back in '78 Wiley said that a species is a lineage of ancestor-descent populations that maintains its identity from other such lineages and has its own evolutionary tendencies and historical fate. I don't know why he had to put the last phrases in; it kind of messes up the idea a little bit. But essentially if you're looking at a phylogenetic tree, what he's saying is there's a start and a finish on a branch. So it has duration through time; that kind of thing.



And then we'll come back to the genetic cluster species concept, which is one that Jim Mallet put forth. Basically it says if you can get a lot of genetic data on the things that you're looking at, and you plot them out into gene space somehow, and you find that they form distinct clusters, then each separate cluster is a separate species.



Now each of these is useful in a somewhat different context. And, as I said, I think that they all get at parts of what we mean when we say the word species. And I don't want you to forget the question I have hanging in the air, which is do we have to make everything into a species? Okay?



So, concepts and criteria. This I know looks a little weird. Okay? Why do they distinguish between concepts and criteria? Because after all criteria are concepts. Okay? This is because they were trying to achieve kind of a local clarity in what they were talking about. So the concepts are more or less general statements about how you might go about thinking about what a species is, and the criteria are rules of thumb to decide whether a thing is a species or not. So you can think of the concepts as being abstract and the criteria being practical.



So we've got these concepts. And here are a few criteria that could be applied to any concept. So one would be, why are the things separated? Is there initial separation? And of course if we want to go into it, we can look at the causes, but maybe the most important thing is just that they're separated, not why.



We can look at whether the species is cohesive in some sense; there are different definitions of cohesion, but one is, is there genetic mixture? Are they breeding with each other? So cohesion has something to do with the biological species concept. Another is, is that--are the organisms in the populations that we're looking at monophyletic? I'm going to come to the definition of monophyly today, and I'm going to repeat it next time, so that it gets hammered in a little bit. But basically that means do they all share a common ancestor?



And then there's the issue of distinguishability; can we actually tell them apart? Now when we get down to cryptic species, at the end of the lecture, you'll see that they are indistinguishable, except at the genetic level. We can't look at them and see any difference. But for many things these will be useful criteria.



So, monophyly. The things in monophyletic groups share a common ancestor, and that common ancestor is not the ancestor of any other group, and there aren't any things that are descended from that ancestor that aren't in this group. Okay? So it's really everything that came from that common ancestor. So birds all appear to have shared a common ancestor that split off from basically a group of dinosaurs, back in the Cretaceous; possibly a little earlier, in the Jurassic. Mammals all split off earlier from a group of organisms whose later descendents then included the dinosaurs, but also many other things in that grade.



In contrast to a monophyletic group, a paraphyletic group is a group that doesn't contain all the things that are descended from the most recent common ancestor of its members. Okay? So yes, everything in here has a common ancestor, but hey, there's some other things that descended from that common ancestor that are out here.



So, for example, if you call fish a natural group, you're making a mistake because the tetrapods are descended from the same ancestors as the ancestors of everything you want to call a fish. So the amphibians, the reptiles--I'll come to the reptiles in a minute [chuckles]--the birds and the mammals are also things that we ought to call fish--okay?--by that definition.



So we need a different word to reflect the history of relationship. In the reptiles, the birds and the mammals are missing. Okay? So if we say reptile, and we want to really refer accurately to a Tree of Life, a good phylogenetic tree, then that word should actually also mean, oh, we mean the birds and the mammals too. The thing that's going on here is that our everyday language culturally evolved before our scientific discoveries demonstrated what the natural relationships of groups were, and therefore we have embedded in our everyday language mistakes. So that's why these distinctions have been drawn. They are pointers to mistakes. So if somebody says paraphyletic, it's like that's a mistake.



Then we have polyphyletic, which is another kind of a mistake, and a group is polyphyletic--the word referring to that group is a mistake--if the things in it are descended from several ancestors that are also the ancestors of things that are classified into other groups. So, for example, all the stuff that Linniaeus called worms was highly polyphyletic. It included the mollusks. It included therefore the octopuses and the squid.



If you were to refer to the Old World Euphorbiaceae and the New World Cactaceae, among the plants, as being in the same group because they look the same, you would be wrong, because they both have--they're actually fairly distantly related from each other and they have converged on Cactus-like forms, and they have closest relatives that don't look anything like a Cactus. So if you ever make a group like that, that would be polyphyletic.



Are there any questions about these three distinctions, or have I managed to get across those differences clearly enough? Because this is--it's important; it's simple but it's important.



Okay, species concepts and criteria were reconciled by Kevin De Queiroz, and basically what Kevin did was more or less arrive on a scene where people had been embroiled in controversy over species concepts, and he wanted to kind of stop all of the squabbling about the concepts and try to move the research on by more or less trying to resolve that, and do so in a constructive way.



He did a pretty good job. Basically he said, "Hey, let's see if we can agree--not everybody does--but let's see if we can agree that species are entire population level segments of lineages, from origination to extinction." So they have duration in time, and they're at the level of a population, and we could map them onto a Tree of Life.



And the criteria aren't the same as concepts. Basically what they're doing is they're marking stages in the existence of a species, and they don't actually determine whether the species is a species yet. Okay? Now, as we'll see, if you actually go through what's going on as a species starts to evolve, on the Tree of Life, and you mark off these species criteria, I think you'll see that much of the time, by the time you've stepped through all your criteria, you have a good species.



Okay. What are they? Well there's separation. There's cohesion, and the cohesion can be genetic and caused by actual or potential interbreeding. It can be cohesion of recognition; so everybody who is a potential mate can recognize each other as a potential mate. It can be a cohesion of viability and fertility. So there's post-zygotic compatibility; very important to include a lot of plant species there.



Then there can be ecological cohesion. So these things are living in the same habitat, at the same time, behaving as an ecological unit, and very probably doing so because they are actually inter-breeding. By the way, this business of remaining separate, in the same place, is a good criterion for two separate species. So if you see two things that are remaining separate, even though they are continually running into each other in the same time and place, then that's a pretty good indication that they're separate species.



So another criterion is monophyly; so they share a single most recent common ancestor. And then you can distinguish them either through fixed morphological differences or as a phenotypic cluster in phenotype space--this is a more quantitative thing than the quantum differences of distinct morphology--or they could be a genotypic cluster, in a genotype space.



Now when you think--I'm now going to lead up to a bit on the genetics of speciation, and this slide is intended as a transition into that, and it is intended to show you basically that gene trees often differ from population trees. So what's going to go on in a speciation event is that you're coming along the Tree of Life and there's going to be a split and there are going to be two new branches. And these are entire populations down here. Okay? So you should think of each branch down here as having thousands of organisms in it.



And what these lines are showing you is that there are splits in gene trees that can start occurring before the population splits, and that can continue to occur after the population splits. And what we mean by a gene tree split is actually a couple of possibilities. One is, okay, a mutation occurs here at a locus, and we now have two different alleles that are in this population, and these two different alleles then can continue to be maintained by various processes, and one of them ends up going down this branch, and then the descendents of this one end up going down this branch. That's one possibility.



Another possibility is, oh, we have a gene duplication even here; so we now have two different versions of the gene. They both are being used for something. They're functional, they don't become pseudo-genes necessarily, and the descendents of one copy--actually in that case you ought to get both copies going down both branches of the gene duplication event. So that would probably be more like this.



I suppose that it's conceivable actually that you could lose a copy and still have functional organisms, if the process of acquiring function for the second copy was still going on in this region of time here. At any rate, the point here is that if you look back to try to find the last common ancestor of different genes, or different alleles, it's quite possible that that last common ancestor for the genes will be deeper in time than the last common ancestor of the species; and that's because species have lots of genes. Okay?



So if we look at that kind of process, here is a separation point where, after this, each of these branches is going to be monophyletic. At this point some of the genes have become fixed. So by showing that this one is gone over here--that's just intended as a symbol, an analogy, to indicate that a gene has become fixed--and over here in this lineage maybe some other one has become fixed, and at that point genetically these species are distinguishable. You can tell them apart because now one lineage has one version of a gene, and the other lineage has another.



Then as these genetic differences accumulate, later in time they will be reproductively isolated from each other. If two individuals of the two species did meet, they would not be able to have viable grandchildren. And of course I've shown you that that reproductive isolation can occur at three different stages. It's likely that the sequence in which reproductive isolation is acquired is actually the reverse of the sequence that I laid it out. So it would be first post-zygotic isolation; then post-fertilization isolation; and then finally pre-zygotic isolation, with recognition that the two things are different. Okay?



And then finally up here, no hybridization at all is possible and you have complete genetic isolation. So you would think that this might be--with reproductive isolation that you wouldn't get any hybrids, but there could be a few mistakes, and so finally complete gene exclusion is usually coming after what is in practice reproductive isolation. This is a bit imperfect.



So if we look into the genome, and this has been done best with Drosophila, because it's such a good model organism--and this is, if you want to go into this kind of thing, search under C.I. Wu, that's Chung-I Wu; he's at Chicago. And basically what Chung-I said was that if we look across a genome--okay, so you can think of A, B and C just being as markers on the genome--there's gene flow between two populations at lots of places in the genome as speciation just is starting to get going. Okay?



So at this stage we have populations or races. They've got perhaps different kinds of adaptations. There isn't any reproductive isolation, and between these three loci there's lots of recombination; the three loci are actually capable of moving back and forth. So A and a can move back and forth; B and b, and so forth.



Then, in the second stage, there starts to be some block to gene exchange, and here we are at a level where we're getting a transition between a race and a species, or between a race and sub-species, with some degree of reproductive isolation, and at this stage the populations could fuse or they could diverge. But these blocks here, that you're seeing, are indicating portions of the genome where there isn't any exchange anymore.



So the idea here is that the origin of reproductive isolation, if you look at the genetic level, is a gradual process; it doesn't occur all at once. It starts in parts of the genome, and it continues, and while it is developing, there's some still some gene exchange going on, at certain loci. And you might think--and I think this is probably the case--the parts where the exchange is still going on are the parts that aren't having big impact on hybrid inviability or mate recognition. The parts that are starting to get frozen up are the parts that have to do with any of those three levels of separation.



So when reproductive isolation is complete, then all of the genes are free to diverge. So here the populations are beyond the point where they could fuse but--and they're a good species--but there's a still little bit of hybridization going on, that you can pick up, and here they're completely separated and there's no gene flow anymore.



Now Chung-I did this actually with simulans, Drosophila simulans, Drosophila mauritania, and the two sexual races of Drosophila melanagaster, which are in Africa. Okay? And he looked through the genomes of these species to see at how many places were there genes that were diverging, and what were those genes coding for? So the differences between the two sexual races of Drosophila melanagaster, which are really quite recently separated--we're talking perhaps 50 or 100,00 years here--are all in sexual behavior. That's things like how fast does the male vibrate his wings?



And Stage 3, which is about here, is between simulans and mauritania, and here we're starting to get back maybe 500,000 years, something like that; and here we're starting to pick up lots of sterility and inviability or female sterility genes, and changes in genital morphology so that lock/key mechanisms are incompatible. And then finally when you get this divergence here, which is back at one to two million years, basically you just see a lot more genes in these categories; sterility and inviability accumulate.



So how does a new species actually come into existence? Well going from that rather modern evolutionary genetics, back a bit to the arguments in the '40s, '50s and '60s over speciation, a lot of that argument is about geographic speciation. Darwin emphasized allopatric speciation. Gulick, who worked on the speciation of snails in Hawaii and Polynesia, emphasized allopatric speciation. Sympatric and parapatric speciation are things that came in, in the '60s and '70s. Allopatric means allo-patric, different places; sym-patric, same place; para-patric, next to each other.



And genetically, as you've seen from Chung-I Wu's analysis, initially there are only a few genes that are changing. So even though you have 35,000 genes in the genome, speciation might be driven by four or five, and that's what might allow it to occur fairly quickly. And then after reproductive isolation, the changes in those genes mean that all the others will diverge. So a good criterion for a species is, as I told you, they remain separate when they're living in the same place and encountering each other at the same place and the same time.



So let's take a look schematically at what these terms mean. So in allopatric speciation you have an original population. There's some geographic or geological barrier that forms. They then start to diverge in isolation--so here they just start having different colors--and then after they might come back together they won't breed again, because they've diverged so much.



So the classical large-scale example of this is the ratite birds. Those are the flightless birds of the Southern continents, and they include the Ostrich, the Cassowary, the Emu, the Kiwi, the Elephant Bird of Madagascar, the Moas of New Zealand. And arguably those are all birds that originated from a common ancestor that was on Gondwana, and when Gondwana broke up through plate tectonics, these just rode around on the plates. They never flew and they never swam. Okay? So they were actually carried on pieces of rock into different places.



There are, by the way, many other things that can form barriers. Mountain ranges can go up, and when they do, river basins can change, drainage basins can change. Things can become reproductively isolated when they fly out to an oceanic island, and so forth.



Now parapatric speciation means next door, right next door. So some individuals of a population get up and they move and they just go right next door. This is thought to have been actually how the Galapagos finches might have speciated on a single island. So some of them might have simply gone up the mountain, while others stayed down on the coast. That would be parapatric speciation. It is also thought to have been what has driven the speciation of frogs in the Eastern United States, and is still in the process of going on.



So, for example, in the Leopard Frog, on the East Coast of the United States, you can breed individuals from Connecticut and New York and they do just fine. Now that frog has a range that goes from Canada to Georgia, and if you try to breed individuals from Quebec with individuals from Georgia, they won't. But all along the way you can make the crosses, which means that it is possible in principle for a gene from Quebec to end up in Georgia. So according to the biological species definition, it's a species, but in fact it's in the process of splitting up. Okay? And by the way, this pattern is something that got re-established after the glaciers melted. So the frogs moved north, and this pattern has gotten set up in the last 12,000 years, about. Oh, I should go back and do these guys.



Okay, that's parapatric and this is sympatric. Sympatric is particularly interesting because the controversy over this was so violent and it involved some of Ernst Mayr's Ph.D. students rebelling against Mayr; so that was Guy Bush. And basically the idea behind sympatric speciation is that it's possible for a population, where all of the organisms are living in the same general place and encountering each other at the same general times, to split according to ecological processes that are going on in that little area.



The initial example was a fruit fly that switched from living on apples to living on cherries, where the apple trees and the cherry trees were all in the same orchard, And because the offspring were imprinted on the smell of the fruit in which they grew up, when they grew up, they tended to go to that same kind of fruit, and because mating took place on the surface of the fruit, they became reproductively isolated and they started to diverge. The name of this one is Rhagoletis, and its sympatric speciation has actually been documented and followed, and it's occurring in Michigan. You'll see later, we have an example from fish in African lakes where it looks like this is going on.



Now pushing experimental evolution from questions of microevolution into questions of macroevolution is not easy, because by definition macroevolution describes phenomena that are taking place over longer periods of time. Nevertheless, there have been attempts to cause speciation to happen in the laboratory. They have mostly been with short-lived fruit flies, and I'd just like to summarize some of that experimental evidence so that you can see how close people have come to actually being able to create new species in the lab.



If you do divergent selection in allopatry--so you split a population in two and you don't let any gene flow occur between them, and then you select strongly on one trait in one direction in one population, and in the other direction in the other--you can actually cause reproductive isolation to evolve; you can do that in a couple of hundred generations. If you select them in the same direction in allopatry, that doesn't seem to work.



If you destroy the hybrids, when they are in sympatry, and you divergently select in sympatry, that usually works. So you can start the speciation process in the lab, in sympatry, by destroying any hybrids between the two things that you're trying to make diverge, and selecting those two things in different directions, morphologically. But if you divergently select without destroying hybrids, that almost never works. Okay? So there is an experimental biology of speciation, and there is a literature on that. This is something that's particularly been done in Spain, by the way.



Now recently there has been some recent evolutionary theory on whether or not sympatric speciation is possible, and it does appear that it's possible, and it can occur rapidly if you have divergent selection to different habitats, and you couple that with preferential mating with your own ecological type. So this kind of thinking has mostly been applied to fish, and it's been applied to sticklebacks living in lakes in British Columbia, and it has been applied to cichlids living in lakes in Africa. Let's take a look at some cichlids in Africa.



So here are two cichlids that are recently derived from the same common ancestor and often classified into the same species. They are Tilapia. They're living in a lake in Cameroon. This is male size versus female size, and so you can see that there are basically two clusters with a few intermediates. There are some little males and females, and there are some big males and females, and you tend to find the small ones in deep water and the big ones in shallow water.



And if you look at the frequency with which you find them in deep and shallow, you can see that you only get the small ones in deep water, and there are a few of the big ones in deep water, but most of the big ones are in shallow water. You'll notice--by the way, it's darker in deeper water, and you'll notice that the ones that are the small ones living in deeper water already are evolving bigger eyes, and there's starting to be some reproductive isolation between these.



So this is a circumstance in which there is a different ecological habitat; there are different foraging and sensory specializations that are needed in the deep habitat than in the shallow habitat. These guys are probably feeding on snails on the bottom, and these are probably feeding on plankton in mid-water. There is good reason for these two not to cross, because the intermediate phenotypes aren't nearly as good; okay, they aren't ecologically as good, they don't perform as well in eating snails or in foraging for zooplankton.



So that's sort of the classical ecological speciation hypothesis. Dolph Schluter at British Columbia has written a whole book on this. There's a big literature on it, and a lot of people are interested in the idea that there could be some sympatric speciation going on.



Now we saw that these species criteria work fairly well for a certain range of organisms, but then there's also the genotypic cluster thing, and that really solves a problem with asexual and cryptic species. So I'd like to just introduce you to that issue.



One context where it's useful actually is with bacteria. So here are a whole bunch of bacteria that all live in the gut, enteric bacteria, gut flora. And these guys are all pretty proficient at horizontal gene exchange. There's about 30% of their genome that they exchange back and forth, pretty freely, so that there's a lot of recombination going on across most of this tree here. But the housekeeping genes of these bacteria don't exchange horizontally so well.



There's a core group of genes, and they are the genes that are responsible for energy metabolism and the construction of ribosomes and cell walls and stuff like that, that actually form a core that doesn't participate in horizontal gene exchange. And if you just concentrate on that core of genes, you get a perfectly good phylogenetic tree. It forms a gene cluster. If you include the 30% that are being horizontally exchanged, the whole thing gets very fuzzy. So that gene cluster definition is good in bacteria, if you concentrate on the core genes, which are housekeeping genes.



There is a radiation of salamanders, Batrachoseps, in California--well studied by Dave Wake's lab at Berkeley, by the way--where there are a very large number of species and local forms, and many of these can only be recognized if you look at gene sequences. So cryptic species are common in some groups of salamanders. Cryptic species are also common in the algae that coral farm. So reef-building corals have endosymbiotic commensile algae that they farm, and the strain of algae and the strain of coral have a lot of cryptic diversity. You look at it and you can't tell the difference from the outside. There's a lot of diversity like that, out there in the world.



But this is really one of the most interesting cases of a cryptic species, Tetrahymena. So this is a ciliate, and there are ten morphologically, completely indistinguishable forms that had a last common ancestor about a hundred million years ago. So these things are a good example of stasis. They still look exactly the same. Okay?



However they have diverged a tremendous amount in their DNA sequences, and interestingly even though they look exactly the same, the proteins that build those structures have diverged. It's like there has been really strong stabilizing selection to keep those things looking the same, even though the genes, and the proteins that build them, have diverged. So that's deeply cryptic, and there's things like that out there. So there are cryptic species.



So first, evolutionary biologists have come up with a bunch of different species concepts. It's like the Hindu tale of the blind man and the elephant, and one of them touches the trunk, calls it a rope; one of them touches the leg, calls it a tree. They're all coming from slightly different perspectives; they're emphasizing different aspects of the process.



What is helpful in thinking about a species tree is that a species is a segment of a tree from start to finish, and if you're thinking about gene genealogies, a species is a population that is monophyletic and it is distinct from other similar populations that are monophyletic.



The criteria you might want to think about, if you want to sit down and logically distinguish two populations and call them different species, are separation, cohesion, monophyly and diagnosibility--can you really tell differences? And I've just shown you--sometimes you can only see the differences in the DNA sequences. And these criteria do mark stages in the divergence of lineages.



The genes that are involved in speciation start off few in number. You might only need to be influencing some aspect of hybrid inviability or some aspect of mate choice and behavior; perhaps just changing the frequency of wing fluttering or something like that. But then, over time, the number of genes involved increase, and other kinds of reproductive isolation mechanisms evolve. And then there are these very cryptic species that can only be distinguished as clusters in genetic space.



Now if you get interested in this stuff, here's some--I've stuck this in, so you'll have this for reference--the January 20, 2009 issue of Heredity has ten articles on the genetics of speciation. Jerry Coyne and Allen Orr have a good fairly recent book on speciation. You can also, if you want to, search for Trevor Price, Dolph Schluter, Sergey Gavrilets, Ulf Dieckmann, Michael Doebeli; and you'll pick up books and papers on recent speciation ideas. And next time we're going to take this basic element of the Tree of Life, which is the separation of the branches, and start looking at phylogenetic systematics.



[end of transcript]

The Tree of Life must be discovered through rigorous analysis. Genetic information is crucial because appearances can be deceiving, and species that look similar can prove to be genetically very dissimilar and not share recent common ancestors. Two criteria, used to determine what the "correct" Tree is, are simplicity and whether the tree maximizes the probability of observing what we actually see.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 13

Transcript



February 16, 2009



Professor Stephen Stearns: Very good. So today we're going to talk about phylogenetics and systematics, and the lecture has this kind of structure. I'll remind you of what the Tree of Life looks like. Then I will motivate the lecture basically by giving you some surprising recent results from molecular systematics, and then I will go into basically what phylogenetic concepts are and how to build a phylogenetic tree. I won't do this in great detail, but I hope I do enough of it so that you at least have a good feel for the issues that are involved when you do this.



So this is the same picture of the Tree of Life that I used earlier in the course, and basically it shows you that since about 3.5 billion years ago, there have been three large clades that have developed. [Technical Adjustments] Take a moment and look at this picture, and look at the next one--which is a--this next one is essentially a blowup of what's been going on since about here--and think about how much that tells us about biology.



It provides a very basic structure, the structure of relationships. It tells you which things shared common ancestors, and why we might expect them to be one way rather than another way. It sets up thousands of comparisons in our minds about questions that we might ask. It provides an extremely useful, overarching structure. But the question is, how did phylogenetic biologists actually get this picture, and are they still changing it? And the answer is: they got it with the methods of inference that I'm going to sketch today, and they're still changing it.



It's not written in stone and it's been changing ever since the first time somebody tried to write it down. So these things are working hypotheses, and we are able to get a better and better refinement of them as new information comes in, but there are significant changes.



Now this is what Darwin had to say in the Origin about the Tree of Life. It's a truly wonderful fact, the wonder of which we are apt to overlook from familiarity, that all animals and all plants, throughout all time and space, should be related to each other in groups. And he goes on about how these groups are hierarchical. He said, "The affinities of all the beings of the same class have sometimes been represented by a great tree. I believe this simile is largely the truth."



So in this beautiful Victorian prose, Darwin rhapsodizes a bit about the Tree of Life, and it was the only picture he had in his book. Okay? So he thought it was real important. He made a sketch of it, and by it, by this sketch, he meant to indicate that a lot of things had gone extinct and that through ancestry and shared common ancestry you could define relationship.



Now he could see immediately that the tree isn't given, it should be discovered. He said, "Our classifications will come to be, as far as they can be so made, genealogies;" So they will reflect what actually happened in terms of evolutionary history to generate relationship; "and then they will truly give what may be called the plan of creation. The rules for classifying will no doubt become simpler when we have a definite object in view. We possess no pedigree or armorial bearings." Okay? That's mid-nineteenth century code for there's no barcode on the species. Okay? They're not wearing their name on the forehead and they're not telling you who they're related to. So we have to discover and trace these diverging lines.



Well it actually has taken a long time for phylogenetics to settle on clear logic and clear methods. Up until about oh somewhere around 19--the ideas were there but they weren't really implemented until about 1965 to 1970, and there ensued a huge controversy that lasted for about twenty years. And now that all--the dust has settled and that seems to be in the past, but many people actually my age are still marked by it, because we witnessed it.



And I'm now going to more or less summarize what came out of it, but I just want to signal to you that this was, in the not very distant past, an extremely controversial area of science, and that it was revolutionized both by the advent of DNA sequence data, and by the development of powerful mathematical and computer methods for determining relationship; and there was an argument about which ones we should use.



So the first step in that is taken by a guy named Zimmermann, and it's just sketched here, and it seems very simple: Sharing a more recent common ancestor defines relationship. So magnolias and apple trees are more closely related to each other than either is to a gingko, because this point on the tree is later in time, and connects them, than this point on the tree, which connects them to gingkoes. It seems like a very simple idea. It wasn't really clearly articulated until Zimmermann laid it down as a principle in 1931.



Now some of these concepts you've already been through. So I'm going to simply mention these names again, just so that they get repeated and start becoming part of your own vocabulary. Monophyletic is a group that contains all of the descendants from a single common ancestor and nothing that is not descended from that common ancestor; paraphyletic groups are groups that do not contain all of the species descended from the most recent common ancestor; and polyphyletic groups really are a hodgepodge of stuff that shouldn't be in that sort of bin, under that category at all, because they have--basically independent evolutionary lines are being incorrectly lumped together.



The basis of a lot of this inference is the concept of homology, and homology and analogy--I'll repeat them in a minute when we get to some slides that illustrate them--but they were defined by Richard Owen in the early nineteenth century, before Darwin's Origin of Species. He was a great morphologist, in London, and basically the idea of homology is that a trait is identical in two or more species because they are descended from a common ancestor. So they got it because their ancestor had it.



And homoplasy, or convergence, is similarity for any reason other than common ancestry. So convergence in morphological traits, mutation to the same sequence, in DNA, will lead to homoplasy. So homology is helpful, and homoplasy is confusing in determining phylogenies.



So here's a good monophyletic group. Okay? This is the dogs. And here the dogs are. Here's Canis and Lycaon--so the Lycaon is the African Hunting Dog--and their closest relatives are the South American wolves. Canis, by the way, Canis--the timber wolf is in the genus Canis, and all domestic dogs are descended from wolves, which is a nice example of really rapid evolution; take a wolf, turn it into a Saint Bernard and a Chihuahua. I give you 5000 years. Can you do it? Well it takes pretty tough breeding to do that, but you can.



And, by the way, I had a colleague--Armand Kuris, who's at Santa Barbara, decided he was going to create his own race; he wanted to create the ugliest dog in the world. He was going to name it the Louisiana Swamp Dog. It took him six generations. I mean, this dog is really ugly. [Laughter] But it's registered with the American Kennel Club. So you can do rapid breeding with dogs. That's, of course, on a timescale up here that you couldn't even fit onto that little white line at the top of the picture. Interestingly, all this stuff over here is extinct.



There are a few little marks here that are kind of interesting. Out here, on the branch going up to the Caninae, is digitigrady, which means that at that point they started chasing after things that were running fast, and evolution, just like it did with horses, started to cause them to be selected to run on their toes. So they got longer legs by running on their toe tips, rather than on the pads of their feet directly. And bone cracking came in right about here, so they could get the marrow out of bones.



That's a good monophyletic group. You probably can't see it up there. I'll give you a little bit of timeline. The whole thing starts taking off about 40,000,000 years ago, in the Eocene. And Canis, the dog genus itself, is about 5,000,000 years old; it's about as old as Homo.



Okay, here are some paraphyletic groups. Reptiles is paraphyletic. Okay? It's got turtles, lizards and crocodiles in it, but it doesn't have the birds. So reptiles is an inaccurate term. This is the monophyletic group--lizards, crocodiles and birds--and we don't have an everyday language term for it. Crocodiles, by the way, build nests and guard them, and when the baby crocodiles hatch out, they cheep like birds: "cheep, cheep." So there are--this relationship between crocs and birds is well established.



Here's a polyphyletic group. If we define a group called the homoeothermic tetrapods, it contains the birds and the mammals. But look at all of the things that are more closely related to the birds than the mammals are. So if we were to define the birds and the mammals as a group, it would be a false group, because phylogenetically the birds have many things which are more closely related to them than the mammals do. And this group is polyphyletic. Okay? It has contributions from two different sources.



Another good example of a polyphyletic group would be if you decided to link together all of the things that look like cactuses in Africa and South America. The ones in South America are cactuses, but the ones in Africa are euphorbs; they look just like cactuses. There's a nice example in the Peabody Museum. You can look at them sitting next to each other. Okay? That's a polyphyletic group. They are convergent, they came together.



Similarly, the homeothermy in the birds and mammals is convergent. The ancestor back here did not have warm blood. It evolved twice, once in the line to mammals and once in the line to birds. I know there were some-warm blooded dinosaurs, but that was later. Warm-bloodedness probably came in, in this line, about here somewhere; don't know exactly.



Then this central concept, homology. Here are the forelimbs of turtles, humans, horses, birds, bats and seals. So we've got some stuff here that's spanning quite a bit of the tetrapods; vertebrates that are living on land. And you can see that it's possible to match up sections of these structures, all the way through. And actually if you study that, and you realize that they were all in an ancestral condition together, you can see how evolution has changed their proportions, changed their thickness, but it hasn't changed their spatial relationships to each other.



And, in fact, if you go through the development, you'll discover that the same nerves coming out of the backbone are running to the same parts of the limb, and all of those conditions have been held together, over evolutionary time. And if you look at the HOX genes that are controlling their development, you can see, as you saw in a lecture a little bit earlier, that the DNA sequences in the HOX genes, that are telling it whether to make a humerus, a radius, an ulna or digits, are actually homologous in their DNA sequence as well. So there's a molecular homology that underlies the morphological homology.



And if you look at molecular sequences, here's a gene called aniridia in humans, and a gene called eye-less in fruit flies, and only six--these are not DNA sequences, this is protein sequence; so these are amino acids--only six of the sixty amino acids are different. The two sequences are 90% identical. There are search algorithms, like BLAST, that go out and look for these sorts of similarities. So that if you get a candidate gene or a candidate protein sequence, it's possible simply to put a search term in, to a search engine, and have other genes from other species pop up. So you can look for molecular homology that way.



A good molecular homology is the fruit fly homeobox complex and the human HOX complex--we talked about this earlier--where the sequence of the genes along the chromosome, and the parts of the body that are being controlled by those genes developmentally, are similar in humans and in fruit flies, and actually unite everything that you see here. So this sort of thing is a signal of shared ancestry, and it's the kind of molecular information used to construct the broader Tree of Life. So this is something that is linking together arthropods, annelids, mollusks, echinoderms and chordates.



Now analogy. Analogy or convergence is a misleading kind of information, because that means that natural selection has taken things that were evolutionarily independent, and which have sister groups, have relatives, that don't look anything like this, and then shaped both of those things to come together to a common form. So the dolphin and the ichthyosaur have a very similar fusiform body, and this is because of strong selection to swim rapidly in the ocean and to chase down fish and squid; which they both did.



And the analogy goes deeper than that. As you probably know, the dolphin has live birth, it's viviparous. So is the ichthyosaur. If you go to a striking museum, just south of Tübingen, in Germany, and look at the world's largest collection of pregnant ichthyosaurs, you can see an ichthyosaur that was giving birth at the point when it was fossilized. And they often had twins, or triplets.



So the definition of analogy is two things that look very much alike, even though they have many relatives that look quite different and are distant on the tree. So the dolphin is more closely related to a kangaroo than it is to an ichthyosaur, and an ichthyosaur is more closely related to a hummingbird than it is to a dolphin; nevertheless they look similar. So that's analogy.



So once people got their DNA sequences and their logic under control, and they started doing a lot of molecular systematics, they discovered some relationships that were kind of surprising, because analogy, convergence, had been covering up relationship, or because evolution had so radically changed the external appearance of these creatures, that it was very difficult to see who they were related to.



Here are a few of these insights. I'll bet that if I ask Alex or Jeremy or Katie or the other teaching fellows if they've got a favorite one, that they could probably come up with others as well. Maybe I will in a minute; so start thinking. Okay?



Pentastomids were a mysterious group of creatures, and they turn out to be closely related to fish lice. I'll show you a pentastomid in a minute. There used to be a group called carnivorous plants, the pitcher plants and the sundews, and people thought that the pitcher plants and the sundews were related. These are plants that are adapted to living under very low nitrogen conditions, and they need nitrogen to make all of their proteins, and they get it by killing insects and other things. Some of them can even kill a small frog. So it was thought that it was likely that this was a natural group and that they had all evolved these capacities in an ancestral condition, and that they were all related to each other. But they're not. It's happened several times.



It wasn't really clear where the whales had come from. One might have thought that well maybe whales are related to seals, or perhaps they're related to other aquatic mammals, like otters. But seals and otters are carnivores, and it turns out that whales, including the toothed whales, the active carnivorous dolphins and sperm whales, are ungulates. Okay? So there was an ungulate that used go around eating plants and it went into the water and it started to eat all kinds of other things. Okay? It stopped eating plants and it started eating fish, squid; and some of them eat a lot of crustacea, if they filter feed.



Sycamores. Sycamores, or plane trees, are the classic tree which is used to decorate the European plaza. Okay? If you like to sit out in the summer, in Italy or France, and watch the people go by, you're probably sitting under a sycamore tree. And they have a leaf that looks like a maple leaf, and if you just look at a sycamore--and by the way it has a kind of blotchy bark; so it has sort of white bark but with blotches on it--if you just look at a sycamore and you just look at the shape of the leaf, you might think, "Oh, these are related to maples." They aren't at all. They are in fact more closely related to water lilies.



Now those are some pretty radical surprises. Those are things that were buried in the DNA sequences, that were not apparent in the morphology, and they are not only testimony to the power of molecular systematics, they are testimony to the power of natural selection to change the shape of things in ways that are profoundly altering and create all sorts of mis-impressions about relationship.



So here are some pentastomids. This set of pentastomid worms here is actually crawling across the roof of a crocodile's mouth. They tend to live in the noses of crocodiles and dogs. They don't tend to live in humans, this is one of those yucky, creepy-crawlies that you don't have to worry about too much yourself. But it looks--actually it looks something like a beetle larva, or something like that; it looks kind of like a mealworm. But look, it's got segments in it, and it has some kind of funny structure inside.



It turns out that it's most closely related to this thing. Here is a fish louse on the outside of a triggerfish, and this is an isopod. Pentastomids are related to fish lice. They are not related to beetles, or to nematode worms, or to a lot of other things. And, in fact, they're nested within the fish lice. So evolution took something that looked like that and turned it into that. And like a lot of things, this probably was accomplished by things like crocodiles eating things like fish. And when the parasite that was living on the fish got ingested by the crocodile, it was more or less, "Oh my heavens, how am I going to adapt to the crocodile?" Well if it could fall of the fish and stay in the mouth of the crocodile and crawl up its nose, it can survive; which essentially is what these things did.



Here are two carnivorous plants. Okay? They are polyphyletic. Pitcher plants have evolved independently at least three times; flypaper traps at least five times. There are two groups of pitcher plants that are sister groups to two clades of flypaper traps; but others have other sister groups. So these are actually deeply cool plants.



The world hotspot of pitcher plants, if you have a deep desire to go collect a lot of pitcher plants, is Borneo, and it is no coincidence that Borneo is an island that has very, very nitrogen poor soil, and the trees and all the shrubs that live on Borneo, many of them have special adaptations to dealing with this low nutrient environment.



Things like flypaper and the sundews, the flypaper traps, they often live in bogs, which also are extremely nutrient poor. If you go to Bethany Bog here, you will find these living in Bethany Bog. It's a kettle lake that was left after the glaciers retreated. There's a mat of vegetation growing out over it, which means that in the middle of it, the plants are living right over water. The water is nutrient poor, and there are flypaper traps catching flies out there, to get their protein.



This is a chunk of the Tree of Life that shows you the radiation of the ungulates. And you can see that both the toothed and the baleen whales are nested within the ungulates, and their closest relatives are the hippos. So you should think that the ancestor of the hippo went into the ocean, probably about 35,000,000 years ago, and right here, marked on the tree, are some of the genes which have changed along these particular lines and which are signals of those relationships.



So the take-home point is that appearances are deceptive and detective work is needed. Now how do you do the detective work? How do you build a phylogenetic tree? Before I do that, do you guys have any favorite sort of phylogenetic--you have; Jeremy what's yours?



Teaching Fellow: Yes, gnetales, not being related to flowering plants, for me personally. Because gnetales have double fertilization, which is a very interesting innovation of plants, or flowering plants have. And actually ginkgos are gnetales in the gymnosperms, the pine trees. That personally--we learned that from Burleigh and Mathews [a paper published in 2004].



Professor Stephen Stearns: So how recently was that discovered?



Teaching Fellow: Like three years ago; three or four years ago.



Professor Stephen Stearns: Okay, see, the tree keeps changing. It's a moving target. It gets better. The basic branches are not moving too much, but out there on the tips there's still a lot of action. So how do you get it? How do you build a phylogenetic tree?



Well this is an important point. You need to have some characters; so those are states of traits. They could be nucleotide sequences. It could be whether the thing has scales or fur, or it could be whether it has a three or four-chambered heart. It could be a lot of things. So you need characters, and they need to have different states. And the characters that are informative are shared derived characters. I will go into this issue with a full slide, because this is a key point; the characters that give you phylogenetic information are the ones that everything in a group shares with each other, and it's different from the ancestor.



Well, you can only define derived by comparison with primitive. Okay? So primitive is like what it used to be, and derived is what it is now, somewhere on the tree, and you can't do that without a tree. So there's kind of a paradox. You don't have a tree, and if you don't have it, you don't have a way to determine what came first, and therefore you don't know about character polarization. Character polarization means knowing which state is primitive and which is derived; that polarizes that series of trait states. So there are number of ways out of this logical dilemma.



One is you look at all possible trees--this is, by the way, a huge computational problem, as you'll see at the end--and you choose the ones that are simplest. So that's the principle of parsimony. And it's a logical principle; it's not an empirical principle, and it's not necessarily the way that evolution operates. But given that there are many, many possible trees, choosing the simplest one basically is a way of saying, "This is how we're dealing with our ignorance."



Or you could choose the tree that would make it most likely that you would have observed the character data that you actually did observe; that's called the principle of maximum likelihood. And, in fact, in the computer programs and in the theoretical arguments that go on in phylogenetics, these are two of the main themes, and many of the methods combine them, in various ways.



Okay, so a bit about shared-derived characters. Remember that picture with the different colors, with the different parts of the forelimb? Having a forelimb that has a humerus, a radius, an ulna, carpals and metacarpals, in that sequence, really doesn't help us to distinguish bats from turtles. Okay? That trait's shared among all tetrapods. So the fact that you're looking at a thing, that's got those parts to it, doesn't help you to distinguish bats from turtles from whales from seals. Sure, they've all got it, but that's not telling you whether they're closely related to each other or not, because they all got it from a common ancestor; it's not derived.



However, that structure distinguishes the tetrapods from the lobe-finned fishes. So at that point on the tree it becomes useful as a shared-derived marker, of a group; which is why, one of the reasons why, we're pretty confident that the tetrapods is a good group, and that things didn't- that the vertebrates didn't come out of the water multiple times. In this context it's marking a trait that originated once in their common ancestor; it's shared by all of them; it's not found in their closest relatives.



The jargon is derived from the Greek. This thing is called a synapomorphy. Syn means shared; apo means derived; and morph means trait. So a shared-derived trait is a synapomorphy.



Now there's a bunch of important stuff here. Just looking the same isn't very helpful. The informative traits are the ones that are shared and derived. And what is shared and what is derived, and therefore what is informative, depends on the context; it depends on the part of the tree that you're sitting in.



Okay, now a little bit about building trees. You can think--evolution is real complex and a lot of stuff is going on. But let's suppose that A has the ancestral state of a trait, and that between A and B and C, a new state of the trait evolves. So Ancestral is blue and New is red. And this marks the point where that trait started to change, and then it spread through the population and by this point it was fixed.



Well this is a cartoon, and this is a cartoon of a cartoon. Okay? We're just marking where that happened, and the only important thing about this mark is that it is between this point and this point; other than that, we don't really know exactly where it is. Okay?



Now A, B and C would normally be species. Okay? But they could be other things. They could be genes, or they could be genera or families or something like that. And 1, 2, and 3 are characters. They could be morphological; they could be molecular. And, as a convention, the ancestral state of that character will be denoted 0, and the derived state will be denoted 1; and the arrow indicates going from ancestral to derived. And basically what this picture is telling you is that Trait 1 changed from ancestral to derived, between A and B, and then after B split off from C, two more things changed in C. Okay, so that's the information that picture is trying to give you.



And if you put down a real interesting vertebrate phylogeny, like this, a vertebrate phylogeny which has some unfortunate names, for certain groups on it--okay?; like reptiles aren't real--and we use these characters, having a vertebral column, having lungs, having an amniotic egg, having lactation, eggshell absent, chorioallantoic placenta, hooves on distal phalanges, a petrosal bulla, in the skull, then what we can see from plotting those along the line basically is which characters here are distinguishing which groups; what's going on when you go out into the ungulates, the horses and the cows.



The vertebral column is a synapomorphy of the vertebrates, of this whole bunch here. But if we just look at the mammals, which are from here on out, it's an ancestral trait; it's not a derived trait, it's a shared-primitive trait, and that's a symplesiomorphy, not a synapomorphy. The lungs, which come in right here, at 2, are a synapomorphy of the tetrapods, but they are an ancestral trait, a symplesiomorphy of the amniotes; okay, so the amniotes are back here--excuse me, the amniotes are up here. So whether you call a trait one or the other depends on where it sits in the tree and what it allows you to do with it.



This is a bit of the relationship between trees and names. Ideally we would like that relationship to be totally clear and unambiguous so that if I just give you a name, you know where that thing sits in the tree. This is a hard thing to do. It is so hard to do that there is now a complete overturning of the Linnaean System of Classification going on. It's being led by a couple of guys here, Michael Donoghue and Jacques Gauthier. Michael is in our department, and he's also vice-president of the university, and Jacques Gauthier is a prof in G&G - in Paleontology.



And they have worked a lot on how to get a way to name things that actually tells you their complete position on the Tree of Life. Okay? It's going to be a big computer code. It's not going to be something nice like Homo sapiens. Okay? Homo sapiens is the Linnaean name. The new method will contain a lot more information in it, and will probably only be something that you can store on your iPhone, or whatever else it is that you use to replace your memory.



But ideally these terms would map onto natural relationships; and these terms actually do map onto these natural relationships. Okay? So this is the primates, and these are the ungulates, and they are nested within the eutherian mammals. The therian mammals include the marsupials, and the mammals include the monotremes, which are the spiny echidna and the duckbilled platypus. And between them and the marsupials is where the female reproductive tract evolved, because the monotremes are still laying eggs. And then the amniotes would include the so-called reptiles; that would actually be crocodiles, lizards, snakes, turtles. The tetrapods include the amphibians, and then the vertebrates include the fish, as well. So this is a natural classification, and that's the way all taxonomic nomenclature should be related to all good systematics.



Now, how do you actually infer a tree from a character matrix? So here we're just trying to figure out if things are related or not. We don't have a tree yet. Okay? And we have three species and we have three characters; and in this case ancestral is going to be 0 and 1 is going to be derived.



Well this particular character matrix is consistent with drawing a tree this way, and then marking down the transitions here. So when 1 went from ancestral to derived, it changed here in both B and C, and when 2 and 3 went from ancestral to derived, it changed only in C. So can you see how the tree relates to the matrix? Okay? Any question about that at this point? I've made the simplest one I could.



Now if we did it with overall similarity, A and B share five ancestral counts. Okay? In three traits, 1, 2 and 3, A has got the ancestral state. In two traits, two of those, in B--B has also got the ancestral trait in 2 and 3, and that would suggest this tree. But if we go by derived similarity, then we get this tree. And you can see what it does to the tree. So this is overall similarity, which is misleading, and this is shared derived trait phylogenetics, which yields this tree, and it shifts the sister of B from A to C.



Now if life were only so simple. Life is never simple. Traits can conflict with each other in the information they give you, and they often do. So here is a character matrix with no conflict, and here's a character matrix with conflict. Okay? So everything was looking pretty good, as long as we'd only measured Trait 1 and 2 down here. But then we measured Trait 3, and Trait 3 seemed to indicate that C had this ancestral trait over here. It was beginning to look like C was going to be a highly derived species. But then we've looked at another trait and it wasn't like that. What do you do? Right? What do you do?



Well you can choose the simplest tree. You can choose the one that implies the least change. So here are all trees which are consistent with this character matrix. And if you go back and try, I think you will see that you can plot all of these changes onto here. So basically this tree is saying that third trait down here, it changed twice; it changed once in A and it changed once in B. So it went from an ancestral state up to a derived state, along these branches. And these traits up here, 1 and 2, they changed between A, on the one hand, and B and C on the other, here. So you could do that also, and you would find that all of these trees are actually consistent with that character matrix, but this one takes five changes and these only take 4: 1, 2, 3, 4; 1, 2, 3, 4, 5.



Therefore, we come to the conclusion that one of these traits, one of these trees, is probably correct, just by the principle of parsimony. And the only way that we really resolve this kind of issue is by getting more data. The more data you get, the more likely it is that that will converge on the real tree. I would like to point out that there probably is not enough data in the world to do that, for all of the creatures on the planet. In other words, at the end of the process there will still be some unresolved stuff.



Now what about--let me just put that in--what about this? Where does the root come from? Well these are unrooted trees, up here, and the choice of where you decide the ancestral state is actually makes quite a bit of difference to the tree. I'm sorry that in translating this has gotten screwed up a little bit here. This is actually A over here, and then it goes D, B, C over here. Choosing this as the root, rather than this, changes the relationship from B and D to B and C; this is B and this is C; this is B and this is D. So where do you get the outgroup, how do you decide where the root should be?



Well, that issue can only be decided in the context of a bigger tree. So you must have some other kind of information to suggest what your out group might be. And, when this is actually done, sometimes people see whether the choice of an outgroup is actually going to be changing the shape of their tree very much. They will report, "We tried this and this and this as the out group, and these were the results, to our tree." Okay?



Now, you get your trait matrix, you want to find the simplest tree. One of them is to do an exhaustive search. So here are two terminal taxa, B and C. Okay? We've chosen A as the ancestral condition; it's not an existing species now. A, we say, is going to be the out group; that's going to be link to the ancestors. Only one tree possible. If we have three terminal taxa, we can have either B as the closest relative of D; C as the closest relative of D; or B and C as being their closest relative. So there are three possibilities there.



If we have four terminal taxa, oh my goodness, suddenly we have this many. Oh that's confusing. If we have 500 terminal taxa, we have 1 times 101280 possibilities. This is a combinatorial explosion of possibilities. And about, oh say about 2003, 2004, it took nine months of runtime on a supercomputer to sort out all of the possible trees for a reasonable number of characters for something like this. So if you have 500 species and you wanted--and you had a reasonable number of characters, you would only get a tiny fraction of those trees covered, and you would wait nine months to get your answer. It's gotten a little better than that recently, but not much. Okay?



So there are ways to get around this problem. There are all kinds of heuristic ways to get around this. There are ways of jumping into tree space and doing local approximations and then branching things together. So that, for example, when the New York Times reported last week, on Darwin's birthday, that biologists had recently been able to publish a tree of 11,000 plant species, which was done here, by Stephen Smith and Michael Donoghue's group; he did that as a super-tree, using these approximation techniques to patch together lots of smaller trees. And there are all kinds of criteria that get applied to how good that is. By the way, one of the things that Stephen turned up is that hey, the ferns are still evolving rapidly; which is kind of neat. Lots of other stuff is in that.



So, the Tree of Life is not given. We have to discover it. The informative characters in the Tree of Life are those that are shared and derived. So appearances deceive. Simply looking similar is insufficient information. You can make a lot of trees with the same character matrix. You would prefer either the simplest, which implies the least change, or the tree that maximizes the probability of observing what you actually see, or some combination of those criteria. Okay? Next time we'll take these methods and see how we can infer history with them.



[end of transcript]

We can use methods of genetic analysis to connect phylogenic information to geographical histories. Human migration has left genetic traces on every continent, and allows us to trace our roots back to Africa. Molecular genetic methods allow us to determine whether or not trait states were ancestral, which can have profound implications for fundamental biological ideas.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 14

Transcript



February 18, 2009



Professor Stephen Stearns: Today we're going to talk about these phylogenetic trees that we've been discussing for the last couple of sessions; and this completes the three introductory lectures on methods that are used, or basic concepts that are used in macroevolution. So we began that with speciation, so that you can understand where the branches on the Tree of Life came from. And then we had a quick overview of how to construct a phylogenetic tree, so that you could see how the whole tree was put together. And now we're going to see what happens when you either lay these trees onto maps, or you put traits onto the trees, or you do both at the same time. This is basically comparative biology, in its modern sense.



The outline is first a bit about looking into time; using phylogenetic trees and looking into geographic history. Then we'll look at how we can map traits onto trees and draw some surprising conclusions. And then we will put trees together with traits and put them on maps and see what that tells us actually about evolutionary ecology of lizards on Caribbean islands. And then we'll end with a take-home message from comparative biology, which is that species are not independent samples, and that because they're not independent samples, we need special methods for trying to assess how frequently things evolve in the Tree of Life. And that will lead us into both looking at how seeds do in sun and shade, in related species, and the issue of whether you should be more faithful to your mate if you're going to be married to her for a long time.



Okay, well let's start with some of Godfrey Hewitt's work. And this has to do with what happened in Europe after the glaciers melted. Now just to remind you about what Europe looked like at the peak of the last Ice Age. The glacier came down out of Scandinavia and got down about into Northern Germany and Poland. The English Channel was dry because there was so much water that had been locked up in the continental ice sheath that the level of the earth's oceans dropped about 100 meters, and at that point there was a sub-glacial tundra that stretched essentially from Ireland all the way across France and through Russia, out into Siberia.



So there was pretty much--it was called the Mammoth Step. And at that point many of the animals that you now find in Northern Europe had retreated south, into glacial refugia. There was one in Spain, there was one in Italy, there was one in Greece and the Balkans, and in Asia Minor. And you can now take the mitochondrial DNA out of these various organisms that are plotted here, and you can reconstruct where they spent the last Ice Age, and how they got back into Northern Europe.



So, for example, most of the grasshoppers of Northern Europe came out of the Balkans, and the ones that spent that time in Spain never got over the Pyrenees. The hedgehogs managed to get over the Pyrenees and spread through France and Belgium and the Netherlands. However, about at that point they met the hedgehogs that were moving north from Italy, and there were a bunch of other hedgehogs that were coming up from the Balkans.



The bears, interestingly, managed to do just fine, getting out over the Pyrenees, and they moved right up into Scandinavia. And up in Northern Sweden they have met some bears probably that had been in the Ukraine and had come out from north of the Black Sea; and so forth.



So it's possible, using mitochondrial DNA, molecular phylogenies, to reconstruct the recent history of movements of animals across the planet, and trees, across the planet, and to understand why it is that there are certain places where we see hybrid zones. And in fact here are some hybrid zones, in Europe. These are places where you will frequently run into hybrids, and they are there because populations are coming back together that had been isolated in the Ice Ages and breeding with each other.



So, for example, this is one I know pretty well, because I went there for thirteen years. There's a spot in the Swiss Alps, in the eastern part of the Swiss Alps, just north of the Italian border, or just south of the Austrian border, right about here, where almost every flowering plant that you see is a hybrid. And the guidebooks are just lousy, they just are horrible. It's extremely difficult to identify what you're looking at. But when you see the big picture, you can understand it. So if you're interested in this kind of thing, this is a good paper to read, by Godfrey Hewitt, and the papers that have cited, that have cited that one; those are good sources.



Now what about humans? Well I'm going to show you first what's happened in about the last 10,000 years, and we're going to see that in Europe the agriculturists spread out from the Middle East and squeezed the Celts into the northwest. In Africa we're going to see the Bantu migration out of Cameroon, and how the Hottentots were squeezed into the southwest of Africa. And in Asia we'll see that agriculturists spread from both the Middle East and from China, and squeezed Siberians into the north.



So these things are laid out in a beautiful book by Cavalli Sforza, Paolo Menozzi, and another author, Alberto Piazza, I believe. And basically what they did was they tried to come up with a method of compressing a huge amount of genetic information onto a map, and they did it by taking gene frequencies, at hundreds of genes, and then compressing them, using statistical analysis, into a few factors, and then plotting those factors onto the map.



So what you can see here is basically the population differentiation of humans, in Europe, and you can see that there is kind of a wave that comes out of the Fertile Crescent and moves up to the north and to the west. And this tracks the agricultural expansion, which started about five or six thousand years ago, out of the Middle East. And you can see that the Celtic genes did get squeezed up into Ireland and England, and out into Brittany, and so forth.



So there are lots of neat details in this book. If you focus in on particular areas, you can see that there's a hotspot, right in Palermo, of Viking genes from the Viking occupation of Sicily, etcetera. Interesting stuff.



If you look at Africa, what you can see is that there has been an invasion of Africa by Caucasoid Northern Africans, and by sort of an Arab Nilotic expansion, coming down this way. The Bantu expansion out of Cameroon is what is coloring part of the continent pretty red. And, by the way, this migration got through here about a thousand years ago. So the Bantu migration down into East Africa is something that is relatively recent.



And if you've been reading about the war in the Congo, and the conflicts between the Hutus and the Tutsis, the Hutus are Bantu, and the Tutsis are Nilotic, and you can see where the Nilotic and the Bantu mix comes together here in the Great Lakes region of Central Africa. So this kind of map gives you some feel for the way things have moved.



By the way, there was a kingdom in Mali, centered around Timbuktu--or an empire--and this orange spot is a relic of that. So the history of human movement on the face of the globe is written in the genes and can, to a certain extent, still be recovered. This kind of study will no longer be possible after another few hundred years of jet travel and crossbreeding. My son, for example, is in a relationship with a woman from here. Another few generations of that and this map will not be reconstructable.



If we look at Asia, what we see is that there were nomads and agriculturists coming out of the area around the Middle East, and around the Black Sea and the Caspian Sea, that have pushed into Central Asia, and the Chinese agriculturalists have spread into Southern Asia.



But there's a very interesting hotspot of human biodiversity in southeastern Asia, going from India over about to Taiwan; and actually this is where the Polynesians came out of. The Polynesians left from Taiwan we think about 5000 years ago, and that's confirmed both in the language reconstruction and in the mitochondrial DNA. That just came out a few weeks ago.



So you can see that one of the themes of recent human history has basically been of the expansion of some groups at the expense of others, and that that was often a technology-driven thing, and often involved agriculture.



Now, I've shown you this before, and I just want to bring this back in again, at this point, to indicate what you can do with phylogenetic trees, and just to remind you. It is now possible to get information on single nucleotide polymorphisms at 650,000 different sites in the human genome, and this is a paper that did that for 928 unrelated individuals from 51 populations. So these are the 928 individuals out here. These names down here are the 51 populations, and the 650,000 different positions in the human genome are on the Y axis, all compressed together; so it's very hard to see any differentiation there.



And you can see that there is certainly a genetic signature across this; certain kinds of genomes in certain geographical areas. And if you then do the molecular phylogenetics on it, and construct the phylogenetic tree, you see that the oldest part of the modern human tree is centered in Africa. This, by the way, is the Classical view. This was a picture that could be drawn in 1995--and this is 2008; so this thirteen years later--and this tree largely confirms this picture. Okay? So you could lay this tree onto this map and come up with something that looks pretty much like this.



What you see here basically is we came out of Africa, we paused in the Middle East. Then various groups moved out of the Middle East. One group went into Europe, thought to be about 40,000 years ago; that's these guys. Other groups set out into Asia and spread out through Asia. And then out of the group that had settled basically in Eastern China and Japan and Korea, one group up here split off. Part of them--actually an early part of this branch--went down here, through Papua, New Guinea, into Australia, and another part went out into the New World. So phylogenetic methods can now be used to give us quite a bit of insight into our own history, as well as into the history of other plants and animals.



Now the Hawaiian Islands are an interesting test case. When we look at something like the human expansion across the globe, it's actually difficult to get precise markers for the times when they arrived in certain places. Archeology gives us some; sometimes we can recover fossil DNA from bones. But in the case of the Hawaiian Islands, at least on the scale of the last 5,000,000 years, we have very precise geological dates.



For example, we know that Kohala Mountain, the oldest rock on Kohala Mountain is 430,000 years old, and that the oldest rock on Kauai is 5.1 million years old; and that's because the islands are made over a hotspot here, and carried on a plate up in that direction. And you can actually lay down, on this plate, how long ago it was that that island was actually sitting down here. And that's nice, because when we then do phylogenetics and we start putting phylogenetic trees onto this map, it gives us some feel for when in time those different branch points might have been.



And that has been done for a number of groups. I'm sure there's now more information. This is about five years old here. And these are three different ways that spiders and some other arthropods and some insects speciated over the last 5,000,000 years in Hawaii. Interestingly, you can see that they all moved down from Kauai onto the younger islands. So they were going from older islands onto younger islands, and they just kept hopping.



And, by the way, if you just continue this island chain up to where it dives into Siberia, there were islands there 350,000,000 years ago that are now getting subducted under Kamchatka, and there are things that are one or two-thousand miles up to the northwest that were once high islands above water. So this hopping movement could have been going on for quite awhile. And, in fact, we think that some of the things that we now see in Hawaii got there about 20 or 30,000,000 years ago, before Kauai came above water. So it's an old process.



At any rate, in some cases things simply moved from one island to the other, and then every time they got onto a new island they speciated. In other cases there were four or five species from Kauai that moved down to Oahu, and then several of them sorted out on Oahu and speciated on Oahu, and four or five of them moved down to Maui Nui, and so forth, and then a lot of them speciated on Maui Nui and moved over to the Big Island; and that process went on.



Another process is one where you have a lot of species on Kauai. One of them moves to Oahu. You get a lot on Oahu, but only one then is the ancestor that goes on to Maui Nui, and you get a lot there, and then one goes onto the Big Island, and then you get a species complex on each of the five volcanoes on the Big Island, that are coming from that one ancestor. So all of these processes can actually be seen written in the genes, and this is all resulting basically from sequencing, either nuclear or mitochondrial DNA.



There are other kinds of questions that you can answer. And this is one that was answered by Anne Yoder, who was on the faculty here. She now is the head of the Duke Primate Center. And Anne has specialized in the mammals that live on Madagascar. And on Madagascar you find a local radiation of things that look kind of like civet cats or mongooses. And the question was, did they come over from Africa separately, or did they all speciate on Madagascar?



And Anne was able to reconstruct the phylogeny of this group of animals well enough so she could lay this tree onto this map and determine that in fact these guys are actually all relatives of mongooses, and mongooses are close relatives of hyenas, and those things have a sister group of civets, and those things have a sister group of cats. And they got across right here.



Now Madagascar split off from Africa about 65,000,000 years ago. It's part of the Tectonic breakup that led to India splitting off, skitting across the Indian Ocean, crashing into Asia, and raising the Himalayas. And so you might wonder, well how the heck does something like this cross a strait which is now more than 200 miles wide?



Well have any of you read Rudyard Kipling's story, How the Elephant Got His Trunk? "Down by the grey-green, greasy Limpopo River, all set about with fever trees"--the elephant child looked into the water, and a crocodile grabbed his nose and pulled it out, and that was how the elephant got his trunk.



Well the grey-green, greasy Limpopo River is right here. And in flood stage, if you go out on the Limpopo River, there are large rafts of trees and vegetation being carried down it, and in a good storm you can put a mongoose on a raft of vegetation and get it out across that strait; so it rafted across, and it probably came out of the grey-green, greasy Limpopo River. Okay? So that's right here.



Now what about issues--I'm running through a series of issues that can be resolved using comparative methods in phylogentic trees. And this represents one of the phylogenetic surprises. There are parasitoid wasps which can be either ectoparasites or endoparasites. The ectoparasites lay their eggs on the outsides of caterpillars, and the eggs hatch and make little baby wasps that crawl around the outside of the caterpillar, and they eat it from the outside.



And they have relatives who are endoparasites. The Ichneumonids are like that. Here's a nice Ichneumonid-like wasp. You can see her long ovipositor. And here she is on an insect larva, and she is injecting an egg into it. And the ancestors turn out to have been wasps that did this.



It had been thought that if you just look at it mechanically, it would be easier to start the evolutionary process off with the wasp just flying around and laying its egg. Right? But in this particular radiation--that may have been the case far in the past; somewhere off the slide out here there may have been an ectoparasitic wasp that was an ancestor. But it turns out that all of these things are endoparasites, and the ectoparasites evolved within that, and then within the ectoparasites you had a reversal again and got some endoparasites out of it.



So if you lay the traits onto the tree, and you are confident of your tree, you can reconstruct the history of an important trait like this; and that's a nice kind of insight to be able to have.



Okay, now I would like to discuss the Anolis lizards. And this is something that a large group of scientists, currently centered at Harvard but with branches in Seattle and in St. Louis and other places, have been working on for about the last fifty years. And they study Anolis lizards because these are prominent, easily observed; you can get a pretty good sample size fairly quickly. And they've done fascinating things. So the Anolis lizards have had a big radiation on islands in the Caribbean, and they have made what are called ecomorphs.



Now these ecomorphs can be grouped by appearance. So if you look at them and you see where they're living and what kinds of grasping appendages they have, basically what the phenotype looks like and how they behave, you can come up with things that live on the crowns of trees; out on twigs; down in the ground in grass and in bushes; between the trunk and the crown; only on the trunk; or down on the ground and going up on the trunk. Okay? So there are six ecomorphs.



And you find them again and again. You find them on many islands in the Caribbean. And it's really tragic that in the middle of winter, up here in New England, you have to be continually flying down to the Caribbean to increase your sample size, okay? And doing that for twenty or thirty years, through many generations of graduate students.



Well, after DNA sequencing came along, you could do their phylogeny. And look just--it's hard to see because the reproduction isn't very good on the slides--but just look at the difference in the color pattern. Okay? So, for example, this is the trunk crown's space. Well, it turns out to pop up here, and here, and here, and here: one, two, three, four times, independently. Or you could take something like the twig form. Here's a twig form, here's a twig form, and here's a bunch of twig forms.



Now what's going on here basically is you're having the independent evolution and the convergence on different islands of these different ecomorphs, among these lizards. And if you take that down and you break it down by island, what you can see is that on Cuba the trunk form, the crown trunk form was ancestral. On Hispaniola, the twig crown form--or no, this is trunk crown and this is crown giant; this is a crown giant form, was the ancestral form.



So these are inferences about what first got onto that island and what first got out to the other island. And then these other things all evolved from that. And what you see from that basically is that it doesn't matter which form of lizard you first throw onto an island; all of the other ones are going to evolve from it. And these are all different species. And we're talking about things that range in size from about that big, up to about that big, and that are differentiated at the level of genera.



So this is really major evolution, which is being repeated again and again, across the Caribbean, and generating essentially--what's going on here is that essentially the same ecological community is being generated again and again, independent of which kind of species founded that group. Okay? That was highly unexpected; people didn't think this would happen. So this means that you're getting the same ecomorphs from different ancestral states, and that means you've got convergence.



Okay, now for an insight from a guy named Joe Felsenstein. And if you want to go back to the original paper, it's in 1985. So this is one of Joe's many contributions to phylogenetics. If you just look at this picture that I showed you the other day, you can see that the red trait evolved in the ancestor of both B and C. Okay? So that means that B and C share a trait. However, in evolutionary terms, it only evolved once.



Now at this point, the reason that red increased in frequency might have been that it was adaptive. Things that had the red state had a fitness advantage. So microevolution was driving it at that point. But then everybody inherited it, and it is not an adaptation to the difference between whatever environments B and C now live in. So if you were to look at B and C now, and you saw that they shared some trait, you wouldn't really know why that was there, until you could get a much, much larger sample size; because you just have a sample size of one, when you're looking at that trait. Okay?



So how do you deal with that problem? Well Joe came up with what he called the method of independent contrast. And in this context a contrast is the difference of the value, the mean value of a trait in one species and its value in another species. And if you look up just at the tips of this phylogenetic tree and you take the differences across the closest related sister pairs, at the tops of the tree, you generate these contrasts. You get X2 minus X1; X4 minus X3; and so forth.



Well the important thing about the contrasts is this. The difference that evolved, after this point on the tree, is independent of the difference that evolved after this point on the tree. You've taken out whatever was there because of the common ancestor. So whatever was going on over in this part of the tree is biologically separated and now statistically separated by this method, from whatever was going on in any other part of the tree.



So this actually is a method of getting the correct sample size, off a phylogenetic tree. And that's very important in statistics, because if you have the wrong sample size, all your statistical tests will be wrong. So this was important for the mental health of people who were doing statistics on phylogenetic trees.



So let's take a look at some approaches that are kind of like that. So this is from a guy named Peter Grubb. Peter was the president of the Ecological Society in the UK. He's a botanist at Cambridge. And what he's done here is plot the log of seed mass of light-demanding seeds, against the log of seed mass of shade- tolerant seeds. And his question was this: Do plants living in shade produce larger seeds than plants living in sun? And he wanted to do a phylogenetically controlled comparison.



So what he's doing here is he's taking essentially the value within a genus, or within a family--the mean value of species within a genus or the mean value of genera within families--for related trees, some of which live in open areas and demand light for their germination, and others of which have seeds that can germinate and survive in the shade. So the open circles are comparing genera within families, and the closed circles are comparing species within genera. And what you see here basically is this.



Plants living in shade do produce larger seeds than plants living in sun, but you only see it in comparison of genera within families; you don't see it in comparison of species within genera. Okay? So the ones that need light and the ones that need shade have just about exactly the same seed size, if you are looking at species within genera. But if you then give them longer to evolve, you go further out on the phylogenetic tree, you compare things between families, where that contrast is possible, then you start to see them moving off the one-to-one line, and the ones that are shade-tolerant have seeds which are falling quite a bit--not all; this is an exception--but quite a bit above the line.



So this is a way not only to answer that kind of question, using the comparative method, but also to get an estimate on how long it takes. It takes a long time to generate that difference, because you only see it at a higher level on the tree.



Now what about the albatrosses and their relatives? These are the Procellariiformes, the Tubenoses. You can see the Tubenose right here--and that's a Wandering Albatross; and you can see the Tubenose right here on this Petrel. And these things have totally different life histories. Okay?



The Wandering Albatross, which has a wingspread of between twelve and thirteen feet, and is probably the heaviest flying bird, it lives on islands in the Southern Ocean. And it mates, usually starting at about the age of twelve or fifteen or so, and it usually will produce an offspring every other year or so, for about thirty or forty years. They mate for life; they're monogamous. And they have very precise homing behavior to their chicks. They lay their eggs on places like South Georgia, Macquarie Island, places in the Southern Ocean.



And some French biologists put a radio collar on one of these Wandering Albatrosses and tracked the mother as she took off to go get lunch, for baby. And she flew north, from South Georgia, and she peeled off towards Australia and flew up the West Coast of Australia, and came back across the Indian Ocean and down the East Coast of Africa, and back down to South Georgia a month later; at which point baby, by that point, was extremely hungry, got a lunch of rotten squid.



And this wide foraging means that they're only going to be raising one child every two years or so; and there are all kinds of adaptations in the infant's physiology to deal with this irregular feeding.



A Storm-Petrel is a lot smaller. It forages much closer to shore. It is not so faithful to its mate. These things are related. Okay? So if you look within this family, can you ask the question about whether or not a long life really is a situation that promotes mate fidelity? The argument there is basically that if you're going to have a short life, there isn't going to be enough time to pick up the advantages that you would get from knowing a particular mate, and adapting behavior to that particular mate, and learning exactly how to be a good parent with that particular mate, rather than with some other.



And if you look across the Procellariiformes; so this would be the Wandering Albatross up here, and this would be a Petrel down here, and you've got some other things in the middle--these are all separate species now; the dots here are all species. And we have here a study in which--you are looking at independent contrasts now, and we're plotting the independent contrasts. So this is the deviation in adult life expectancy from an overall mean, for the whole group, and this is the deviation in mate fidelity from an overall mean.



So the ones that tend to live a long time are more faithful to their mates, and the ones that tend to live, have a short life, are much less faithful to their mates and switch mates. And that's interesting because in fact these guys, the ones that reproduce many times, have much more opportunity. They have thirty or forty years of reproduction. They could go out and they could get divorced and pair again several times. But they don't, they stick together. And the functional reasons for that are things that are not really terribly well understood.



Student: What's negative mate fidelity?



Professor Stephen Stearns: What?



Student: Negative mate fidelity.



Professor Stephen Stearns: Negative mate fidelity is just a statistical thing. They are taking the overall--they've measured mate fidelity on some scale, they've taken an average for the whole group, and then they are asking, how far does this species deviate from the average? So if it's below average, it gets a negative number, and if it's above average it gets a positive number. Okay?



Okay, so now I want to ask you a question that comes right out of molecular phylogenetics, and I want to see whether or not you can actually put together some information that you've now gotten from different lectures. So this is going to require you to piece together phylogenetics and genetic drift. So this is the figure from the Becky Cann/Allan Wilson paper that came out now twenty years ago. It's basically on human mitochondrial evolution.



And what it showed was that all human mitochondria appear to be derived from an ancestor, all of whose closest relatives now--the close relatives now are all out at the tip of the tree--lived in Africa. You don't start picking up non-African members of this tree until you get out to this point, and then you can see that by the time you get way out on the tree, that most of these now are non-Africans.



So assertion number one out of this is, hey, human mitochondria show that we came out of Africa. Well we now know from that paper I showed you more recently, from SNP polymorphisms, that this is an extremely well supported thing, and that we see it in the nuclear genes as well.



But the claim here was an interesting one. It said there was one woman, living in Africa, about 220,000 years ago, from whom all other mitochondria in all humans on the planet are descended, and so they gave her the name Mitochondrial Eve; that's observation number one.



Observation number two--and this now comes from an immunobiology group in Germany--and basically it has to do with how old are the polymorphisms in our MHC genes? And these are things that have been selected, probably through frequency dependent selection, in co-evolution with diseases.



And the observation is this. Say we have two MHC genes that have resulted from a gene duplication--and that would be this one here and this one here--and at each of those genes there is a polymorphism, so that we have different alleles at that locus, for each of those two genes. Who are those alleles most closely related to?



Well it turns out that Allele 1 in humans is most closely related to Allele 1 in chimps, and Allele 2 in humans is most closely related to Allele 2 in chimps. In other words, the closest relatives of the alleles are not in this species; they're in another species. The only possible way that that could have occurred is if the polymorphism originated before the speciation event--okay?--so that you had ancestral species here, and this polymorphism originated, and you got this one coming down from the ancestral species into the chimp, and into the human; and this one coming down from the ancestral species into the chimp and into the human.



Now, on the one hand we have the claim all the mitochondria came out of one person. On the other hand we have evidence that there are trans-specific polymorphisms. And if you take this point in time and you put it on this tree, it's about here. I now want you to talk to each other for a minute, and then we'll see if you can come up with the explanation for how those two observations are consistent with each other. So just turn to your partner and figure it out.



[Students confer with one another]



Professor Stephen Stearns: Silence descends. Enlightenment has been reached. Okay, can anybody tell me why they are not surprised that all of the mitochondria came from one female? Why are you not surprised?



Student: Because they're going to come down through meiosis. It comes down…



Professor Stephen Stearns: It's asexually inherited. How many females do you think there were in the African population 220,000 years ago? Do you think the second observation tells us anything about that, the trans-specific polymorphism?



What happens when a population is really small? You get genetic drift. If a population were as small as one female, it would've been impossible to maintain this trans-specific polymorphism. People have done simulations to find out what is the average size of a population that would, over a period of 5,000,000 years, maintain the amount of trans-specific polymorphism that we see in our MHC complex; in other words, the amount of genes that we share with chimpanzees, where our alleles are more closely related to the chimp's alleles than they are to the other human alleles?



And the answer is the minimum size is about 10,000. In other words, we have good genetic information that tells us that the smallest the human population ever has been, over the last several hundred-thousand years, actually over the last 5,000,000 years, since we shared ancestors with chimps, is about 10,000. Okay? Given that, now tell me, are you surprised that we can trace all the mitochondria, in all the females on the planet, back to one woman, living in East Africa about 220,000 years ago? And if you're not surprised, I want to know why. Yes?



Student: Well you were talking before about how recessive genes spread out in a small population. So if she had enough children over enough generations, you'd have enough of a population [inaudible].



Professor Stephen Stearns: Okay, it's possible that in fact she had a particularly advantageous mitochondrion, and that it then got selected and it fixed, and then everything would go back to her. That's correct. And that could've been done in a larger population. However, it could also have been done with drift, and it happened so long ago that we can't really tell whether it was selection or drift that gave that one woman the advantage.



By the way, the same thing has been done for the Y chromosome. Okay, the Y chromosome is also asexually inherited, and the estimate on the Y chromosome is roughly also about 200,000 years ago, also in East Africa. And the fact that the mitochondrion and the Y chromosome both converged to a common ancestor, at about the same age, might suggest that drift is more likely than selection to explain it.



But basically what's going on, if you think about it, is that in any process like that, if you go back far enough in time, it will always converge on a single common ancestor. Okay? Now the next thing I'd like to tell you is that there was a controversy about when that happened; and the controversy on dating that point of convergence is all about how long has it been since we split with chimps? Because that turns out to be the baseline that gives us an estimate of how rapidly evolution is going on, molecular evolution is going on, in the human clade. Well when you apply that criterion to what the confidence limits on the estimate are, hey, it was anywhere from last year to about a million years ago. [Chuckles]



So the confidence limits are lousy. The observation, however, that that person was in Africa is pretty solid and, as I say, is now confirmed by the nuclear genes, the SNPs that I showed you earlier in the lecture. So the point of this exercise is that when you see results like this, when you see some claim of Mitochondrial Eve, or Y Chromosome Adam--which are both out there in the literature; just go on Web of Science, type Mitochondrial Eve, you'll pick up a lot of controversy about this.



I want you to realize that (a) we should never be surprised if particular mitochondria or particular chromosomes converge at some point in time--it looks like they were just in one individual. That's just because of the way that branching processes work, and that will be going on all the time, and it's happened over and over and over again. So it's no surprise that it goes back to one person.



The other point that I would like to bring out is that if you contrast different kinds of historical evidence, you can often gain enlightenment by seeing that there is a puzzle that needs to be solved. And in this case the puzzle basically is that this tells us something about population size, and this tells us very little about population size.



This process, convergence back to a single ancestor from the mitochondria, it's not entirely independent of population size--it'll take longer in a big population than it would in a small population--but it doesn't give us an estimate of how big the population had to be. Whereas the trans-specific polymorphism could only have been maintained, even with strong selection, in a population that was larger than about 10,000 individuals; and that can be done with computer simulations.



So these are different forms of enlightenment into the history of genes in a particular clade; a history that happens to matter to us quite a bit. And we can gain that by looking carefully at phylogenetic trees. These are actually both phylogenetic trees. This tree here is just laid on its side, and you'll find that this is commoner and commoner practice these days.



If you look at the cover of Nature, or Science, or the--actually the one I remember is in the New York Times Science Section for Darwin's birthday, on February 12th. That week the Science Section had a phylogenetic tree covering Darwin's face, and it had thousands of species on it, and they're laid out this way, just so that you can fit the species onto a piece of paper. So time kind of wraps around, in the way it's presented.



Okay, so to summarize this part of our exploration of macroevolution. These molecular methods allow us to reconstruct geographic movements, as well as phylogenies. And we saw that in the hedgehogs going north from Spain and the Balkans, and we saw it in the humans moving out of Africa, and we saw it in lots of things.



We see that our own migrations have left genetic traces on all the continents. And there's an imprecise map that's suggestive between the genetic geography and the linguistic geography. Greek genes go with Greek family names, from the boot of Italy, up to about Rome, and then stop; that kind of thing. So even in the last two or three-thousand years, you can see that family names and genes have been inherited in similar ways.



We can use these methods to determine which trait states were ancestral and which are derived. And that was particularly interesting in the case of the parasitic wasp, whether it was an ectoparasite or an endoparasite, because it changed received opinion about fundamental biology. And this method that Joe Felsenstein worked out for independent contrast is something that will control for common ancestry, and it can reveal the correlated changes in two or more traits that have taken place since branches in the tree. So it can be used as a fairly powerful method to explore hypotheses in behavioral ecology, evolutionary ecology, and ethology.



So next time we're going to start talking about key events in the history of life; it's the first of three ways to look at the history of life.



[end of transcript]

The history of life and evolution has been characterized by several key events. These events can be grouped as new hierarchal levels of selection coming into play, as biological units coming together in symbiosis and specialization, or in a number of other ways. Other important events are situations of conflict resolution or information transmission, from the genetic to the cultural level.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 15

Transcript



February 20, 2009



Professor Stephen Stearns: Okay, we're in the middle of the section on macroevolution. We've had three lectures about macroevolutionary principles: speciation; how to build a tree; and then what kinds of uses you can put a phylogenetic tree to. Now we're going to do three lectures on different ways to look at the history of life. And the first cut, the first lecture, the one today, is an abstract conceptual view of the history of life, and it looks at it as a series of major transitions in the organization of life and how information is transmitted.



And this is the structure of the lecture. We'll talk about what life is, how we think it originated, the origin of cells and eukaryotes, some other key events; and then we'll summarize with the principles that are involved in key events, in major transitions in evolution.



Well, life is basically anything that has the properties of multiplication, variation in heredity, plus metabolism. So it's not necessarily carbon-based or silicon-based or based on anything else; it has these abstract properties. And what we really mean by metabolism is something about thermodynamics.



A living thing that has metabolism is using free energy that it's getting from the environment, and it's using that to maintain a partially isolated system--it's a local system; your body is a partially isolated local system--and it's doing so to keep it in an ordered state--it's preserving the information that evolution and development have given it--and it's doing so against an entropy gradient. So basically we eat energy and we excrete entropy, and the next time you're looking at the toilet flushing down, think about all that entropy that you're putting down into the system. Okay? So this is what metabolism does.



Now if you try to do experiments in the laboratory in which you're watching the evolution of RNA molecules, or if you try to do in silico experiments in the computer in which you are looking at the origin of structures--and that can get to be pretty sophisticated stuff--you're not dealing with a living system. That's artificial. Because with RNA, we're providing the metabolism, we're putting the ATP and the enzymes into the test tubes, and in programs for artificial life, the things that are evolving in the computer are actually getting their energy basically from the electrical cable that we've got plugged into the wall, feeding the computer.



So if you can get, independent of any human intervention, any system that's got multiplication, variation and heredity--so the basics to make natural selection work--and you can arrange metabolism, then it's going to start to evolve, and it will be alive.



So our problem is to figure out how did this all get going? The first major transition was the transition from an abiotic world to a living world; the origin of life. And to do that we had to get multiplication, variation, heredity and metabolism. And the answer is increasingly that it is likely that metabolism came first, and that heredity and multiplication came second; variation was probably there from the start.



So I'm going to actually dwell on some things that are now chemically fairly trivial, and some things that are logically non-trivial and involve paradoxes. Because this is an area that we know it did happen; and we can now break down the steps in increasing detail, but important things are not understood.



So the environment at the origin. Gosh, I went through this thing yesterday and I got all the words on it, and then I start talking and they're not there. So the environment at the origin. The Big Bang is now dated at about 13.5 billion years. It was just a few years ago it was dated at 20 billion years. So the universe, as we know it, is a big younger than I had thought a decade ago. And in stars, the nuclei of all of the elements were synthesized out of hydrogen, basically, and some of the novae and supernovae created things that are heavier than iron; and a lot of that is important cofactors for enzymes in your body. You could not actually function biochemically as you do if you did not have things that had been cooked up in the explosions of giant stars.



Now the solar system is formed basically from recycled star stuff, about 5 to 4.5 billion years ago, and there's intense planetoid bombardment of the inner planets going on at that time. Nothing living could have existed on the face of the earth, because temperatures were simply too high; the surface of the planet was really a toxic wasteland of boiling lava and very, very extreme temperatures and pHs. The initial atmosphere got blown off. The moon was formed, possibly because of the impact of a large planetoid that hit the forming earth and actually blew a chunk of it off.



And at that point the earth had short days; it was spinning very rapidly. It had condensed from a cloud of stuff, and as it fell in, it brought angular momentum into the system. And so the earth started off with a higher rotation speed than it currently has.



Then about a billion years after the planet forms, the atmosphere is reducing, the temperature has fallen to where liquid water can exist on the surface of the planet. And life probably originates on a positively charged mineral surface, and it seems now likely that it was probably at a deep hydrothermal vent.



So there was a hot high-pressure acid around a positively charged mineral surface. There was a lot of chemical energy at that interface. We don't know that for sure, but this does seem to be the kind of a context in which you can get certain chemical reactions to work, that won't work elsewhere.



So you need the building blocks of life. You need linear lipids; they can make membranes and they can make compartments. You need amino acids to make proteins. You need purines and pyrimidines to make nucleotides. You need sugars and phosphates to link things together. And so there's a branch of Origin of Life research that specializes in the chemical conditions under which you'll get this building blocks.



And then after you get the building blocks, and get them to work together, you need things that will make copies of themselves. So if you can get reproduction, variation in reproductive success, some kind of inheritance, then natural selection will take over. If you can get some kind of primitive genetic molecule, it can get honed into an RNA or a DNA structure. If you can get some kind of primitive cell, with a very simple membrane, then natural selection can hone it into a selective filter, where there are pores in the cell that let certain things in and out, and so forth.



So you have to have--you can start with fairly simple things, and natural selection will refine them fairly rapidly, but you have to start with at least these simple things. So that's kind of a bootstrap operation. You've got to get those first replicators up and running before natural selection will take over and create complexity and precision and make it into a sophisticated system.



So how do you get the building blocks? Well there were some very interesting experiments, done by a grad student at the University of Chicago, Stanley Miller, working with Harold Urey, and what basically he did was he would put methane, nitrogen, ammonia, ammonia chloride; he would put in carbon monoxide, nitrogen, hydrogen, different kinds of mixtures, into a vessel, and then he would pass an electric spark through it. And he found that it was fairly easy to get these amino acids to fall out.



And, by the way, most of this guy's Ph.D. thesis consisted not of performing that experiment, but of doing the analytical chemistry afterwards to convince everybody that this was actually what he had gotten. Okay? In 1953, that was not so easy; we didn't have all these beautiful gas chromatographs and whatnot to do the identifications.



Okay, so the basic structure of this is that you make something out of fairly small, simple molecules, likely to be in the atmosphere or in the water, on the surface of the earth, 3.5 to 4 billion years ago. And you give it some energy in the form of an electric charge, or you heat it, or whatever, and you see what comes out. So amino acids are pretty easy.



When I was 15-years-old, I was fascinated by this experiment in high school, and I tried to repeat it, and I blew up the chemistry lab, and I produced a toxic cloud of cyanide gas--which you can get out of these guys--and that caused the evacuation of the entire building, with 200 students sitting outside on the lawn, in the middle of morning classes; it was deeply satisfactory. [Laughter]



Okay, so we have a bit of ambivalence on this issue of abiotic synthesis. Some things we get real easy. Okay? We get amino acids, fatty acids, sugars and purines pretty easily. Some things are hard. So pyrimadine nucleotides; ribose is not so easy. A linear, long-chain, fatty acid, that you might find really useful for making a membrane, that's not so easy. And it's not easy to get these things all in the same synthetic environment. So you have to imagine that well perhaps we're getting different chemical reactions going on in different micro environments, and they're mixing somehow.



But then once we've got the building blocks, you run into what is not a chemical synthesis problem, you run into an abstract logical problem. Okay? That's the error threshold. So the amount of information that you can maintain by selection is limited by copying fidelity. Basically what that says is that if you have a very high mutation rate, you are destroying all of the information that you've accumulated, and you're not transmitting enough of it to the next generation to be able to usefully accumulate information on how to do something better. So that's the error threshold. If you don't really have high copying fidelity, then mutations will kill you.



And if you have a small genome--basically if you have a small genome that's big enough to do something--it can actually have a higher mutation rate than a large genome. A small genome is small enough so that the probability of a mutation at any one place in it is fairly small. A big genome is extremely likely to have a bunch of mutations. So there's a relationship between the size of the genome and the amount of mutation that can be tolerated.



So Manfred Eigen--he's a German guy who got a Nobel Prize for his work in biochemistry--was thinking about the origin of life, and he said, "Well, the relevant mutation rate is non-enzymatic replication. We're going to be making copies of molecules, and at the origin there aren't any enzymes anymore." Okay? Enzymes are things that are produced by living systems; we don't have them. We have to imagine ourselves back into the situation where we don't have enzymes but we want replication.



And for that, it turns out--he did the calculations--the maximum genome size is about 100 nucleotides. So if we're dealing with replication of a DNA-like or an RNA-like molecule, you can only get up to a genome of about 30 amino acids with the kinds of mutation rates you get with non-enzymatic replication.



Well that's much, much too small for an enzyme. You're not going to get an enzyme out of that. Anything bigger than that, you need to make the replication more accurate, and in order to make it more accurate you need an enzyme. You need translating machinery to take the genome and make it into that enzyme; you need the enzyme then to be working on making the genome replicate accurately.



And that takes a lot more than 100 nucleotides; it takes more like 1000 to 10,000 nucleotides to construct any of the things that we know of now that can do that. And so you can't get enzymes without a big genome, and you can't get a big genome without enzymes. It's a catch-22. Where are you going to go?



So Eigen tried to cook up a way out of this, and he called it hypercycles. And the word hyper immediately makes you think of something that's almost quasi-metaphysical. It's nothing complicated. Okay? Here's what a hypercycle is. Each one of these little things here is a chemical reaction, and this little loop that I'm pointing at, where B is making something that's making more B, indicates that B is actually capable of making more of itself; it's a chemical reaction that can make more of itself.



And there are a lot of such chemical reactions. Often, in a chemical reaction, you'll get product out of one side, plus some other stuff that's like what you started with. And this big dark arrow here indicates that some of what B makes is actually a precursor for C. So C needs something that B is making, and it takes it and makes more of itself, and then it ships something on that D needs to make more of itself; and D takes that and makes more of itself and ships something on that makes A; etcetera. Okay?



So if you can set up--it's called a hypercycle because it's a cycle with cycles inside of it; it's a cycle of cycles. The rate at which any one of these can replicate increases with the amount of product that's being given to it by any of the others. And that means that B can make more B if it's getting more from A; C can make more C if it's getting more from B.



That means that in order to function, the elements have to cooperate for substrate. They can't compete for substrate. They have to take what they need and pass some on. And if this is then going to get refined and become more sophisticated, and perhaps get to the point where it acquires an information molecule like DNA, then it has to competitively exclude other such systems.



You could imagine a surface at a hot thermal vent, 3.5 billion years ago, with many different such things; a high degree of variation in just tiny little micro, local chemical reaction systems. And if this is ever going to bootstrap life and get underway, then it has to be isolated in a compartment and start competing with other such systems, because only then will natural selection kick in.



There is a problem with this kind of thing. It's just sitting there in its happy, hot thermal vent, taking its chemical energy out of the environment. And it's open, it's an open system. A selfish mutant could invade and destroy it. Somebody could come in, who was say an alternate version of C, and take stuff from B and make a lot more C, but not ship anything on to D; it could make a lot more C. That would essentially be a selfish act. Okay? That means taking but not giving back.



And in this system here, an altruistic mutant won't spread; and altruistic means taking some and passing enough along. So if this thing is open, and it's not isolated from the environment, any one of these steps in the hypercycle could be invaded by a chemical alternative that would destroy the hypercycle.



So these things are a model. Okay? We're not saying that this is what actually happened, but it is a model of how a small group of cooperating molecules might have evolved, before there was a genetic code. If we could get them to be sufficiently complex, then they would start competing with each other, and then, at a certain point in the complexity, they might invent genes and have a competitive upper hand by then being able to transmit the information on what was working. So that would certainly give them an upper hand in competition.



And they would solve Eigen's paradox, because each one has a small genome, but in sum they would add up to the information in a big genome. So if you could somehow stabilize these small competitive systems so that they had internal cooperation but they were competing between themselves, you could get life going.



So one way out of this problem of the invasion of mutants is to actually put them into compartments. Okay? So you actually have to get the chemical reaction system isolated inside something like a membrane; and that means it's a local group.



Will, are you finding certain things here resonating? Will's a political scientist, and he's interested in the interaction between cooperation within groups and competition between groups. Those basic ideas, that actually resonate in economics and political science, are there in evolutionary biology, right at the origin of life.



In order to get this going, in order to get the whole process going, basically what you need to do is isolate one of those hypercycles, let it grow, have some kind of division going on, with some inheritance, and then have a mutation that's going to improve one of the descendents, so that this one, that has a better hypercycle, can out-compete that one.



Once you get that process going, then you're going to retain cooperation within compartments, you're going to increase competition between compartments, and natural selection can take off and start to produce the very early primitive cells. That's not so easy. You got to get the compartments, and there's some issues about the compartments.



You need them so that you can keep the cooperators on the inside and you can put the parasites and the defectors on the outside; so you can keep the guys that you like and you want to work with in there with you, and you can tell the other guys to go away.



What this does, it's associating cause with effect strongly, in the sense that if you're cooperating and you are shipping your product on to the next member of the hypercycle, that actually is an effect that's retained within the system and then comes back to help you. If it's open, you have no guarantee it's going to come back to help you. So there's no guarantee of reciprocity. But if you can contain the cycle, then reciprocity is going to occur because the cycle is shielded from the outside.



And it means that all of the elements in the cycle have a common stake in the success of the compartment. They are all in the same boat; they're all in it together. If they get better at what they do, together, by cooperation, they will improve their competition with the other similar things on the outside.



Now, we don't know where the long-chain fatty acids came from. So I'm just going to pull them out of the air; we're back in Greek comedy, deus ex machina--a machine lowers a god onto the stage and he gives us long-chain fatty acids. So we have our long-chain fatty acids; and, in fact, we have a special kind. They've got a hydrophilic end and a hydrophobic end. There's a b-o missing there; that's hydrophobic. So one end likes water and one end hates water. And if you do that, if you make those things and you throw them into water--so you have an aqueous solution--this is what you'll get.



These are things which are either micelles or primitive little spheroids or sometimes linear things, that actually start looking pretty much like a biological membrane. The fatty tails are sticking in and associating with each other, and the hydrophilic parts are sticking out and associating with all of those nice charged water molecules.



Well, make a mixture of those things, and then put in a surface--so you have either the water surface or you have a mineral surface--and this is what naturally happens. This is called abstriction; you will get a little bump forming.



We're talking about stuff that's there for free, in the sense that you don't have to have any natural selection going on to give this to you, in the chemical structures. These things, once you get them, will do this spontaneously. Okay? So you can get something like this happening--this is a nice little sphere that's starting to bulge up off the surface--and if you make them big enough, they will divide.



So they will grow and they'll actually kind of start pulsing around a little bit, just from Brownian motion. And if you get these little spheroids, that are lipid bilayers, up to a certain size they will actually divide. So you can see that it might not actually have been necessary for natural selection to arrange the first replication events for cellular compartments. That might have been something that was just happening physically and chemically, so that part of the bootstrapping was there for free.



Making it efficient, making it good, making it precise, making it complicated, that's a whole 'nother story; that took a lot of evolution. But just that very simple initial step of having a sphere of a bilipid membrane that had a hypercycle in it--maybe one in each compartment that would then divide--that was probably there for free.



Now, if you want to make it grow, then one of the things you want to put inside it is a hypercycle that will make more membrane building blocks, because that will just make the thing grow. So perhaps that was actually the kind of chemical reaction that was going on in some of the early semi-cells or proto-cells; they were making the building blocks of lipid bilayers.



However, then you've got a problem of how to get the different substrates that you need in through the membrane; that's the problem of membrane transport. You've got to have the membrane. You've got to isolate your reactions so that they can be cooperative and not de-stabilized by parasites. But once you've isolated them, then you have the problem of moving things in and out through the membrane. So there's got to be a period, back at the origin of life, during which membrane properties can evolve, and that in a replicating entity that's not yet fully cut off from its environment.



And the solution to that, one possible solution is a semi-cell. That would be you make a cup on the surface of water, or on the surface of a mineral, and you don't completely close the perimeter. So the thing's kind of leaky; stuff can go in and out of the edges of the cup. And that will solve the problem. Okay? It allows a partial openness, it gives you a certain degree of control over who comes in and out, and that might've helped to adjust these early semi-cells.



If you want to have a look at a fairly recent article--this is now five years old--Rasmussen was talking about transitions from non-living to living matter in Science. And then this would be a good way, in Web of Science, to go and trace the more recent literature. They will all--all the more recent articles will almost certainly cite this one; and then it also cites you back all the way to the Miller-Urey experiments in 1953.



So there's really growing interest in how a simple life form could be synthesized in the lab, and there is a desire to see whether or not we can understand the origin of life well enough so that we can make alternate forms of life, so that we can make self-replicating and self-repairing nanomachines.



And Drew Endy, up at MIT, runs an international competition every year where bright young molecular geneticists and microbiologists get together and they try to engineer biological machines. And the point of the competition is to try to make the most complex and sophisticated little biological machine that you can. And he's got funding from MIT to bring these people from all over the world. So every year there's an international competition and a team comes in from Beijing and a team comes in from Paris, and if Yale puts one together, a team goes up from Yale, and they all play with their biological machines, which are at the scale of viruses and bacteria.



So out of this kind of creative play, we may actually learn a lot, that then applies back to the real origin of life, rather than the geeky post-modern nanomachine, so I see some hope in that kind of playful research.



Okay, now I will wave my hands and a miracle occurs and it's later on in the evolution of life. We're now going to discuss the prokaryotic/eukaryotic transition. And the prokaryotic/eukaryotic transition is thought to be a major transition because it contains a significant change in the transmission of information.



Every major transition in the evolution of life has consisted either of a difference in the way that genetic information was transmitted and/or in the unit of selection; a thing that was actually evolving. So both of those things are going on here.



What's going on in the transition from the prokaryotes, up here, to the eukaryotes, down here, is--one thing that's going on--is that you're going from an organism, like a bacterium, that has a single circular chromosome anchored to a cell wall, to an organism that has a nucleus within which the chromosomes are--there are then often multiple chromosomes inside the nucleus, plus organelles that are out in the cytoplasm, plus a lot of cell structure that's simply not present in the prokaryotes.



So one of the things that you have is an organizing center, out of which actin filaments will grow, and these are used in meiosis and mitosis. And associated with that organizing center is a little circular chromosome which is actually thought to indicate that this was originally an independent bacterium, and that these actin filaments are evolutionary homologous with a bacterial flagellum.



You have got vacuoles, you've got endoplasmic reticulum; all kinds of stuff. And all eukaryotes, if they have a cilium, they have a characteristic 9 + 2 structure, in the cilium, and this is thought to have been constructed from multiple bacterial precursors, and so forth. So you've got compartments forming, you've got organelles, and you've got a difference in the way that genetic information is compartmentalized and transmitted.



So the prokaryotes have a rigid outer cell wall, they have a circular chromosome attached to the cell wall; and importantly the transcribed mRNA is translated directly. You can see that here. You can see the mRNA coming off of the DNA helix, and you can see little ribosomes here chunking out protein, that are these little squiggly things; whereas down here, that process is being done at the endoplasmic reticulum, and it's not direct, it's indirect.



In the eukaryotes there's an internal cytoskeleton. You've got lots of little micro environments that are giving you the opportunity to create local industry within the cytoplasm. There are several linear chromosomes, inside a nuclear envelope; transcription and translation are separated; and there are organelles. And, with eukaryotes, you get meiosis. So you get a precise and organized way of making genetically different offspring in each generation.



Now, in order to go from prokaryote to eukaryote, you got to lose your cell wall. And that's a real issue, because the cell wall, in a bacterium, is protecting it from swelling up and bursting like a balloon, due to osmotic pressure. So the bacterium is using a rigid cell wall to protect itself from the influx of water. And in order to do that, in order to lose the cell wall, you need something to stabilize it on the inside, and that's the cytoskeleton. So the cytoskeleton is really an extremely important morphological invention in this transition.



Student: Professor.



Professor Stephen Stearns: Yep?



Student: How does this view connect with the fact that cytoskeleton elements have been discovered in bacteria as well? Also cytoskeleton elements are present in bacteria.



Professor Stephen Stearns: Well you would need to have cytoskeleton elements in the precursor, wouldn't you? You couldn't make the transition unless they were already there. If you made the transition without them, you would blow up. So I'm not surprised that there are cytoskeletal elements in bacteria.



Okay, and remember, it's 3 billion years later. So a lot of stuff could've gone on, in the bacteria. I think that what you're on to actually is an interesting system to see whether or not you could actually do experimental evolution. What is the state of the cell wall in this bacteria? Do you know?



Student: [Inaudible]



Professor Stephen Stearns: They don't have a cell wall.



Student: They have a normal cell wall.



Professor Stephen Stearns: They have a normal cell wall. If this idea is correct, then of course it should be possible--it might take a long time--to experimentally select them, to lose their cell walls. But in order to do so, they would probably have to organize their fibrils, their cytoskeleton, in a very precise way before they could do it. Just having them--they're probably using it for some other reason.



Student: They actually--some of cytoskeleton is thought to re-mediate, or regulate, cell wall synthesis.



Professor Stephen Stearns: Is thought to re-mediate--



Student: Thought to regulate cell wall synthesis.



Professor Stephen Stearns: I can't hear the last part of that.



Student: Is thought to regulate cell wall synthesis.



Professor Stephen Stearns: Cell wall synthesis. Some of the cytoskeleton is actually involved in cell wall synthesis. So that would suggest that it was there for a long time. That is actually how evolution works; it invents things for one purpose, and then takes advantage of them for another.



So what you're telling me is actually that this scenario now has all kinds of supporting information, because the bacteria probably had evolved for a long time, using the cytoskeleton for another purpose. But then, having gotten it, they were in a position to use it to keep from blowing up, if they got rid of their cell wall. But they did have to get rid of their cell wall to become a eukaryote. Okay? By the way, I definitely accept the fact that I don't know everything. So I appreciate that.



Now if you put your DNA into a nucleus, and you no longer have it as a single circular chromosome, then it is possible that without having to attach it to a cell wall, it might make it easier to make multiple chromosomes. And you get a big advantage from that in terms of how big a genome you can have, because you can then start replication in parallel, at multiple points, rather than going around a single circular chromosome to do it.



And that means that there really would be no upper limit on genome size. If you can make 100 small chromosomes and start them all off at the same time, in replication, you'll get through the replication step very quickly. So there's an issue about the origin of chromosomes. That's actually a major transition in the sense of how is the genetic material organized



On the one hand there's this replication advantage. Okay? So you can make copies a lot faster if you do it in parallel, in small pieces, than in sequence, in big pieces. And so that would be a cost of having a bigger chromosome. You might want to have a chromosome of intermediate size. And if it's taking an interaction between two or more genes to produce either an organism or to produce a biochemical reaction system that has a certain ratio, that is well balanced in terms of product, then linking the genes that are involved in that ensures that they'll both be found in all of the offspring, and that's a benefit of making a bigger chromosome.



So there would be a tendency for the genome to agglutinate, if this were the only thing going on. But it's balanced by this cost; this benefit is balanced by that cost. And I'm sure there are other things as well; I'm sure you can probably think of some.



Now once you make chromosomes and you synchronize their replication, then essentially what you've done is you have eliminated the competition of the genes. Because by putting the genes onto a chromosome, you've put them all into the same boat. You're no longer getting a situation where one gene might be replicating at a higher rate than another gene, which would lead to unbalanced biochemistry and unbalanced development.



So you've given them a stake in the same process, and that process is the replication of the chromosome on which they are sitting. So particularly for the genes that were involved in replication, if they needed to cooperate to replicate, this would be an important consideration.



Now if you've got a primordial cell that has a lot of reactions going on in it, that are being controlled by genes that are all on separate chromosomes, and if those chromosomes are not being divided evenly at mitosis and meiosis, then it's possible that all those reaction systems are going to get out of balance. Okay? And so if you've got unlinked genes with products that need a certain ratio, then getting them onto the same chromosome and regulating them all together, gives you a big advantage over your competitors, at that point. I'm sorry this is running off. I think it shows up on your printouts.



Okay, now the other thing that's going on in the eukaryotes is they've got these symbiotic organelles that were originally independent bacteria: the mitochondria, the chloroplasts, and possibly the spindle apparatus. So one thing that we notice when we look at the chloroplasts in the mitochondria is that the chloroplasts have a much bigger genome than do the mitochondria, and the mitochondrial genes have been transferred into the nucleus.



We can sequence the mitochondria--we know that they were independent purple bacteria--and we can estimate from the size of the genome of a purple bacterium how much has now been transferred into the eukaryotic nucleus; and we can see that a great deal has been transferred into the eukaryotic nucleus.



So one of the reasons to do that is essentially efficiency. If you put those genes into the nucleus, you're just maintaining two copies of them, rather than thousands of copies out in the population of mitochondria that are living in the cell. Another is conflict resolution. Basically you're cutting way down on the opportunity for different variants to exist in mitochondrial processes.



If you're constructing all of the mitochondria out of essential elements that are in your nuclear genome, you've gotten control over them, in a way, and you are making them all look the same, rather than mutating and possibly having the option of creating a runaway mitochondrial cancer that would destroy your metabolism.



Now why not put all the genes into the nuclear genome? Well there are a couple of reasons. One is that the genetic code is actually different in the mitochondria and in eukaryotes and in the nuclear genome and in the chloroplast. So the tRNA and ribosomal RNA genes, the translation machinery had to be retained in the mitochondrion; at least that much.



Now that explains the mitochondrion, but it doesn't explain the chloroplast. It looks like the chloroplast retains more genes because it has to move macro molecules through more layers of membrane. Remember, the world record on a chloroplast is that it has four membranes around it, and all chloroplasts have two membranes around them. So it's harder to move big molecules through them, and so if you need them to make the chloroplast function, you have to make more of them locally. So that's probably one reason for the retention of more genes in the chloroplast genome than in the mitochondrial genome.



Do we think that the organelles were originally slaves of the things that ate them? Was it a relationship that might have been like a farmer and livestock, the way that corals harvest dinoflagellates, that are helping them make their carbonate skeletons?



Well, there's some evidence. We can look at where are the tapping proteins made that are inserted into the organelle membranes? And those are encoded in the nucleus. Okay? And it looks like they evolve from host proteins. So it looks like there have been manipulative steps where the host was actually tapping in to the symbiotic organelles; that's one piece of evidence.



But there's also thought that they may have been mutualists, and the excretory products of one of them, which was a eubacterium, it was making hydrogen and CO2. And the missing piece of this sentence basically is that that would then have been food for the archaean ancestor of the eukaryotic nucleus. So they could have actually been mutualists. So there is a slave hypothesis and there's a mutualistic hypothesis, and that hasn't been settled.



Why not just have one; why do plants need to have two? And if you look at their ancestors, you can see that purple non-sulfur bacteria and cyanobacteria--so those are the ancestors of mitochondria and chloroplasts--they can do both; they can both photosynthesize and they can respire.



However, the purple bacteria can't photosynthesize when there's oxygen, and the cyanobacteria use the same machinery for both functions, and so that means that the host cell would not be able to separately control photosynthesis and respiration; which one might want to uncouple. And so it appears that mitochondria lost photosynthesis and chloroplasts lost respiration, in coming into the cell.



So I won't run through all of this; you can read through it if you want. Basically what's going on here is the world record for membranes around a chloroplast is 4; it's in a dinoflagellate. And what's going on here is that one thing eats cyanobacterium, and that makes a chloroplast that has the outer membrane of a cyanobacterium and the outer membrane of the cell that ate it, wrapped around it; so that makes two. And then it happens two more times. And so the world record for this is in a dinoflagellate. Okay?



And it turns out that the things that got eaten to make dinoflagellates had separated, so that there were different kind of chloroplasts that got eaten by different things, that both ended up making dinoflagellates. And so it looks like, in that sense, dinoflagellates might be polyphyletic. It's a complicated sequence here. And you will notice in here that you have got some interesting words: rhodophytes; photosynthetic stramenophiles; haptophytes; the dinoflagellates themselves.



It would be worth doing a Google Image search on those things, just to familiarize yourself with this bit of Protistan biodiversity. There are more things out there, in the world, than our fantasies can imagine. And these guys are specialists in all kinds of weird genetics. So I just want to cue you to that.



We're not going to go--this isn't a course in protistology, but there's been an awful lot of interesting evolutionary biology that's gone on in these single-celled creatures. So that's a dinoflagellate. They're cool things. They have a--it's kind of a bit like a small algal cell sitting inside of a complicated glass case.



So there are some other key events: origin of the genetic code; origin of multicellularity; origin of germline and soma; origin of social groups; origin of language. It's a big topic, and in each one of these steps there are several very important things going on, and there are certain similarities of the process in each one of those steps. So I'd like to summarize those, with a few principles that are involved.



So one of the things that's happening here is that there is a new level of selection, there's a new level of replication; the hierarchy is growing. So you go from the hypercycle into competing groups of protocells, and those eventually make a prokaryote.



And then there are symbiotic events, and you actually then have selection operating on a eukaryotic cell that's got two or three genomes in it. And then in the process the genetic material, of course, is also going through its reorganization into chromosomes. And then after that, you get multicellularity; you get cells that are probably genetically almost identical, that are growing together; you get division of labor within that.



So one of the things that happens is that the babushka doll, the number of levels in the hierarchy grows. When that new upper level originates, then there's an opportunity for functional specialization and division of labor. In the multicellular organism we call this division of labor the origin of cell layers and organ systems, so that some cells make brains and other cells make hearts; some do respiration, some do excretion. That would be a multicellular division of labor.



In a social insect colony, we would say that the queen has specialized on reproduction, and then we have the different castes that are doing things. Some of them are cleaning up the garbage in the colony; some of them are feeding the queen; some of them are foraging outside. And you can see the analogy to a human society as well. So there's functional specialization with division of labor.



There is a change in the system of information transmission. So when you go from prokaryotes to eukaryotes, you have to arrange for information to be transmitted, not only in the nuclear genome, but also in the cytoplasmic genomes. And then you have the evolution of meiosis, and you have sexual reproduction; which is a huge change in the way information is transmitted.



Probably since the origin of sex, the biggest- highest impact change in information transmission has been the origin of language and culture, which gives a method of transmitting information from generation to generation, that is independent of the DNA, and allows the process to be going on in different directions at two levels.



Then often in the process of forming this higher level of replication, you have a bunch of lower level units that are coming together to make a higher level unit, and they need to cooperate to do that properly, but they could be invaded by selfish mutants, they could be de-stabilized, and so there's a conflict issue. And this conflict is sometimes stabilized by selection for cooperation.



You've heard me use several times in this lecture a phrase like 'they're all in the same boat' or 'they are all sharing mutual interests', as in the genes getting together on a chromosome, or the chemical reactions coming together in a single protocell.



Those are all principles of conflict resolution, because if you are in a tightly spatially organized system, where your own welfare depends directly upon cooperation with another thing in that system, and your system is in competition with some outside system, and the performance of your system is actually a direct function of how cooperative you are, then there is strong selection for integration, within that group. And it's thought that this is the kind of thing that's going on when you have a key event in the origin of a new higher level in the evolutionary hierarchy.



So those are some of the key events in evolution. They are a rather abstract way of looking at the history of life. And next time we're going to look at major events in the geological theater, and so the lecture next time is more for people who like firecrackers on the 4th of July, and the clash of meteorites.



[end of transcript]

Geology and climate have shaped the development of life tremendously. This has occurred in the form of processes such as the oxygenation of the atmosphere, mass extinctions, tectonic drift, and disasters such as floods and volcanic eruptions. Life, particularly bacteria, has also been able to impact the geological makeup of the planet through metabolic processes.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 16

Transcript



February 23, 2009



Professor Stephen Stearns: Now today we're going to be talking about some of the major events in the geological theater. This is the second of three ways that we're looking at the history of life. The first was rather abstract; it had to do with major transitions and with reorganization of genetic information, units of selection, things like that. That was last time. Today we're going to talk about how life shaped the planet and how the planet shaped life. So this is a quick run through a 4.5 billion year process. And then next time we're going to talk about major lessons from the fossil record.



There are a lot of ways of trying to construct a diagram that will give you a feel for deep time, and it's not so easy. I once did a kindergarten class where I took a bunch of kindergartners and I tried to get them to step off 100 million years at a time, or 10 million years at a time. I think I did 10 million years so that we could take six steps and then meet a dinosaur.



And there are a lot of ways of doing this, but this is not a bad one because it gives you a diagram that shows you about how much of the existence of the planet has been occupied by life; about how much of it has been a story that's mostly of prokaryotes, in other words about half of the time that life has been on the planet, there have only been prokaryotes; and about how much of it has been complicated multicellular organisms. And, of course, we show up just briefly before midnight, on that kind of a scale. So that's one way of looking at it. And learning to think about deep time is really important if you have a taste for macroevolution, and it's certainly important if you have a taste for geology.



Now, at the beginning, we had a reducing atmosphere, and the source of O2 was photosynthetic bacteria. I'm just going to check something here; yes, okay. So we start off with a reducing atmosphere, and then we have to fill up essentially, once the photosynthetic bacteria get going--and, by the way, some of them were chemosynthetic as well as photosynthetic--once the photosynthetic bacteria get going and start producing a lot of oxygen, there's a tremendous mass of stuff on the face of the earth that has to be oxygenated before there's any free oxygen. So that takes quite awhile.



So until about half of the age of the planet, the concentration of oxygen in the atmosphere was less than 0.4%. You would all die within a minute, at that oxygen concentration. And the evidence that we have of when there was free oxygen in the atmosphere is essentially the age of the iron mines of the world.



So there was ferrous oxide--it can dissolve in water--floating around in the ocean, and when the oxygen level of the atmosphere got high enough, it oxidized to ferric oxide, and the ferric oxide fell out of solution, and when it fell out of solution it made the iron mines of the world. That happened 2.3 billion years ago.



This kind of process continued with other sorts of elements. So we have copper coming out at about 1.7 billion years, at a higher concentration of oxygen. And the consequences of free oxygen are that an ozone layer forms in the atmosphere. That screens ultraviolet light and that drops the mutation rate, and it's probably only because the mutation rate dropped significantly with an ozone layer that we could evolve large long-lived organisms.



Once you have oxygen in the atmosphere, you can start getting nitrates. Nitrates are oxygenated nitrogen. So you won't really have nitrogen fertilizer until you have free oxygen, and that then also became a key nutrient for algae. So there's a whole sequence of important chemistry that goes on over a period of about 3 billion years that starts to set up the environment that we're familiar with.



There are a number of ways of looking at this. This is from Don Desmirais, at the Ames Research Center. He's an astrobiologist and has specialized in trying to examine the question of life on other planets; and they have tried to make diagrams like this for other planets as well. So in our early environment, the sun was only about 70% as hot as it is now, and by about 500 million year ago it was up to 95%.



The early environment of the earth was a meteorite bombardment. So if you were out looking at the night sky--which, of course, you wouldn't have been able to do because the meteorite bombardment was so intense that you would've been standing on a boiling lake of lava--but, if you were out, looking at the night sky, on your boiling lake in lava, in your terminator suit or whatever, you would've seen lots and lots of big meteorites coming in every night; and that gradually tailed off. Okay?



The heat flow out of the molten mass forming the core of the earth has tended to drop off and stabilize. So it has a continuous radioactive input, but the original heat from the entire planet being molten has gradually radiated. So we're stabilizing at about the heat flow from the radioactivity in the earth.



And the continents formed and stabilized at about 1.8 to 2 billion years ago, and these things called major orogenies are major chunks of continent coming up and major mountain ranges getting built. Now the collision of plate tectonics has continued to form mountain ranges since then, but this just stabilizing the continental crust took about 2 billion years.



If you look at the history of the atmosphere, of course we're currently worried about the costs: carbon taxes, and global warming, and anthropogenic effects on the CO2 concentration in the atmosphere. But at the origin, the CO2 level was much, much higher. The atmosphere was more than what we would call 100% CO2, because it was thicker at that point, and it blew off. This has dropped down here to about 3 times 10-4 atmospheric pressure for CO2. It's actually a small component.



Oxygen rose and probably reached present levels at about 5 or 600 million years ago. It's interesting that if it went up a little bit more, a room like this could catch on fire, just spontaneously. At about 27%, wood will catch on fire spontaneously, at current atmosphere pressures. So this is another way of looking at that process. At the beginning, we had water, hydrogen, carbon monoxide, lots of steam; a lot of that escaped to space. There were meteorite impacts. The CO2 curve has gone down. The oxygen curve has done up; there's some indications it's gone up stepwise.



Temperature, we don't really know accurately what the temperature was back before 3.5 billion years, but we can be pretty sure that at and after the origin of life, water was liquid on the surface of the planet; so that sets an upper limit of 100 degrees Centigrade. And temperature has gone up and down in a number of cycles over a fairly long period, and there have been some major Ice Ages.



How do you recover that? Well one of the ways that you can do it is you can look, if you have leaves of fossil plants--so if you've already got plants that evolved and they have leaves; so maybe about the last 300 million years or so--you can look at the stomatal ratios on them.



So this has been calibrated. Plants have to make more holes in their leaves; if there's less carbon, they have to have a bigger mouth so that they can feed more efficiently. And they can have fewer holes in their leaves if--and they can be smaller--if there's more carbon in the atmosphere. And so basically this allows you to plot and estimate a curve.



And it looks like there was massive withdrawal of carbon dioxide from the atmosphere from the Ordovician, through the Permian, right here. And then there was a re-injection here, going into the Triassic--and when we come to the Permian Mass Extinction, I want you to remember this dip here, and this re-injection--and then there's been a more gradual withdrawal down to the current level. So the earth was much more of a greenhouse in the past than it is today.



And if we look at where the carbon dioxide went, a lot of it got locked up in limestone, in sedimentary rock. Then a lot of it is in organic carbon. A lot of it is in the ocean, is bicarbonate. These are by far the largest sinks, but there's a lot of bicarbonate ion in the ocean. This is all the fossil fuel on the planet right here; so this is all the coal and oil. And you can see that of the original amount of carbon that was in the earth's atmosphere, that's a pretty small fraction; it's a bit less than 1/1000th of 1%. And in living biomass, there's a very, very small part.



So basically if you look at that, you can see that the carbon balance of the planet is extremely dependent upon what happens in rocks, and that if there are small geological changes in the cycle of how carbon is going in and out of rock, and whether it's being subducted as plate tectonics proceeds or not, is going to make a much bigger difference to the amount of carbon in the atmosphere than the amount of fossil fuel that's being burned, or the tree cover of the planet in forests, which would be the living biomass term down here.



However, this is a slow process, and this is a fast process. So on the scale of human lifespans, this is in fact more important. But on the scale of say somewhere out at around 100,000, out into the millions of years, what's happening in sedimentary rock is really critical.



Now if we look at the way that life structures the planet, one of the very important things that life has done is that it's made soil. And we don't really start to get soil, which is a big complicated piece, an engineered niche that plants create, until we get complicated plants on land. So the first ones on land are probably things like liverworts, and our first fossils are club mosses, and that's happening back at around 400 to 500 million years ago.



There are fossil soils, and those fossil soils have roots in them, and those roots suggest that the first time that there were real trees was at about 350 to 400 million years ago. Remember back to that clock. This is relatively recent, in terms of the age of the planet.



So we get really modern soils with layering, and with evidence of seed plants in the Carboniferous. So that is the age at which most of the coal mines of the earth were laid down; it's about 300 million years ago. If you take Interstate 80, west of New York, and you go out to where it crosses from New Jersey into Pennsylvania, at the Delaware Water Gap, there's a cut there that you can look up at, and what you're looking at is the outwash of rivers that were coming down off of the Taconic mountain range.



And if you look into that cut, it's remarkably clean. It's a preservation of what was coming down rivers 500 million years ago, and it's an indication that there was very little soil. It is basically at or before this process occurs. And that mountain range was formed when Pangaea formed, which is at around 550 to 600 million years ago, and caused the Taconic orogeny, and that put up a mountain range on the border between Connecticut and New York that was about as high as the Himalayas, but it didn't have any forests on it, and it had a very high erosion rate because there weren't plants to stabilize the soil. And we can see, in the Delaware Water Gap, what washed off that mountain range. It's all worn down now, and if we come back in another 500 million years, the Himalayas will all be worn down. But, with the Himalayas, there will be a bit more soil in the outwash.



The guys that have really in the past engineered the planet, and that continue to do so, are the bacteria; and by that I mean both the archaea and the eubacteria. They are the ones that play a huge role in the carbon cycle. They're producing and oxygenating methane. They're fixing carbon dioxide. In the nitrogen cycle, the bacteria are fixing nitrogen from the atmosphere; they fix it as ammonia. They oxygenate ammonia to nitrate; they de-nitrify nitrates to ammonia.



And this is a kind of biochemistry that just about nobody else has. So these are essential things; the nitrogen in all of the proteins on the planet is essentially originating through bacterial processes. So that's how it's getting from the abiotic world into the living world.



There are sulfur bacteria that are arguably extremely ancient, and which evolved in an environment in which much of the energy coming into living systems was coming from things like sulfur, rather than from sunlight, and they oxidize hydrogen sulfide to sulfate; they reduce sulfate to hydrogen sulfide. And iron bacteria are converting ferrous to ferric iron, and they're influencing a degradation of manganese and copper deposits.



A lot of this is now going on at spreading centers at mid-ocean ridges, or it is going on where there is heat flow which is taking ocean water through the ocean crust, and there are bacteria that are sitting just below the ocean crust that are sitting in a stream of basically hot chemical soup that's coming through, and when they do these reactions, often they leave a metal deposit behind; which is why the floor of the Pacific Ocean is covered with manganese nodules that people are thinking about mining at a depth of about five kilometers.



If you go down into the earth's crust, it turns out that the biosphere extends below our feet several kilometers; bacteria are active that far down into the soil, and they are carrying out things like this. So they are really key players in structuring the environment in which we live, and they do a lot of services that we simply take for granted and frankly hadn't even noticed until about the last hundred years of so.



Okay, so those are all aspects of how life has modified the planet. How has the planet modified life? Well there are at least three or four big chapters here. One is through continental drift; another is glaciation; mass extinction; and then local catastrophes. And continental drift and mass extinctions are both out there at the scale of hundreds of millions of years.



Glaciation has two scales. There are times in the planet's history when it's been relatively cold; basically there've been at least three times when it's been really quite cold. But within those longer periods that are cold, the glaciers have come and gone many times. So the North American glaciation lasted 2.5 million years, and the glaciers came and went about 15 times, in North America.



The local catastrophes, it all depends on which particular kind that is. You'll see that they occur at different time scales. The point of all of this is that often the past configuration of the planet, whether it's the location of the continents, or the temperature of the earth, or whether you could expect to live in a secure environment, have at times been extremely different from what we currently see.



And so it is not only important, if you want to understand evolution, to cultivate a sense of deep time, it's also important to cultivate a sense of different time; sometimes deep time was really different, and that's what I'm trying to get at, by showing you these things.



So here's the last 400 million years of continental drift. And, by the way, people are producing models that can now take this back to about oh a billion years. Of course, the further you go back, the harder it is to reconstruct it, because the continents have come together and come apart, and come together and come apart, in a long-term cycle several times, and in so doing they kind of wipe out the traces of their history. So it's really quite a feat to try to reconstruct it.



And I'd just like to point out a couple of things here. This is Gondwana. So Pangaea was a little bit earlier than this; that was when all of the continents were together. South America and Africa and Antarctica and Australia stuck together--and India--stuck together for awhile, before they came apart.



There is an interesting thing going on right here. Here's New Haven. If you go out to Lighthouse Park in New Haven, you'll see some rocks there, and if you trace where the closest relatives of those rocks are, on the other side of the ocean, they're in Rabat, Morocco. Okay? So you can actually see the same kind of rock on the other side of the ocean. And that's when that happened; that's 250 million years old.



Anybody know how old East Rock is? East Rock's 225 million years old. When the Atlantic opened--you see the Atlantic opening here--there were a series of rifts that opened up, one of which became the Atlantic; another one became the Connecticut River Valley.



It didn't open, but it went part way, and then it had a valley filling lava flow that filled it up, and then the flow tipped, and it tipped pointing west, and it cracked in a number of places, and that's what's East Rock, West Rock, and all the other such formations that go up through central Massachusetts to southern Vermont. That was a big lava flow; filled up a big rift valley. So that happened right here.



Now when Gondwana split up, it had some things living on it. The ratite birds, and they are flightless and they don't swim, and essentially they got rafted around on pieces of rock. And it's interesting, if you think about when Gondwana split up, it indicates that the ancestor of these birds was already alive and living across that range of geography, at that point. And you can lay a molecular phylogeny of the ratites onto these continents and it just ties them right together. Okay?



There's another thing that happened with the breakup of Pangaea. Laurasia went north, Gondwana went south. In between, for awhile, there was a thing called the Tethys Sea. And this is the configuration of the continents about 50 million years ago, in the Eocene. By the way, the Eocene was quite warm; it was really a very tropical period.



And at that time there was either--there was a warm kind of Mediterranean coastline that stretched from eastern North America, through Nepal, what is now Nepal, into what is now eastern China. This was before India rafted north and Africa came north and closed off South Asia.



And this is what is thought to have accounted for some of the similarities in the plants that you find in the Appalachian Mountains and in China. And there are many affinities here. The rhododendrons, viburnum; there are a number of tree species that share a phylogenetic relationship across that huge geographical distance, and it's thought to have been the signature of a corridor along which seeds could move 50 million years ago.



Now how about glaciers? Well here is a fairly deep timescale. So this is the Phanerozoic; the Phanerozoic is the term for everything that's happened since the Cambrian started. So this is the Phanerozoic here. So this is at about 500 million years. This is about 600 million years, and there's evidence for one which is deeper, at about a billion years. So this is an Ice Age, this is an Ice Age.



It looks there was an Ordovician Ice Age, it looks like there was a Permian Ice Age, and then there was an Ice Age just in the Pleistocene. So about five Ice Ages. Interestingly, this one, which came before the Cambrian, may have been a time when the earth was almost entirely covered with ice. There are signatures you can find in the rocks of what latitude you're at, whether you're close to the equator or not, and there are other signatures you can find in the rocks that give you how cold it was. These are usually in the form of isotope ratios for things like oxygen and carbon and stuff like that.



And at this point the entire earth may have been a snowball, and only the things that were very, very close to the equator may have come through, because if it really was a snowball, then there was ice covering the world's oceans. That is an interesting issue, and it's one that will probably cause people to speculate and publish for quite awhile, because it's so hard to resolve; there's not too much data, it's a long time ago.



The Permian glaciation, however, is much better studied. Remember that in the Permian, Gondwana is still together. It breaks up at about 225 million years ago; somewhere between 225 and 250. Well the Permian is at 250; about 251 I think. And there was a southern ice cap that was on- actually connected, and actually these continents were all together; and you can see from the arrows the direction in which the ice was flowing. And I think it's really cool that you can find rocks, from Africa, that were scraped off by the glaciers and deposited in Brazil.



Before plate tectonics came along, nobody had any idea how that could have happened. And if you stand on the top of Table Mountain, in Cape Town today--which is something I recommend that any of you that have the opportunity to go to Cape Town do; it's really a very beautiful place--you can still see the grooves in the rock from where the glaciers moved over Cape Town; they're 250 million years old.



The climate since then has actually mostly been warm. So this, if you look on this set of maps--this is 50 million years ago; 35 million years ago; 15 million years ago; middle of the Pleistocene, about 1.5 million years ago; and very close to today, mid-Holocene would be say about 5000 years ago--and you look at how much of the planet is temperate and tropical, look at how tropical the Eocene was.



That was all tropical rainforest, and the Oligocene was still- there was still a huge area of tropics, and the Miocene still had pretty good tropics. But at the last glacial maximums, the tropical rainforests were reduced to a few patches. We're living today in a relatively cold, relatively dry world. That's what we think is normal.



If we were to come in a polar orbiting satellite and look down at the planet say 20,000 years ago, 30,000 years ago, we would've seen that where we're sitting right here is under probably about a mile and a half of ice. The leading edge of it is pushing stuff off of the continent that becomes Long Island and Block Island and Martha's Vineyard and Nantucket; that's the terminal moraine of this glacier.



Scandinavia and Northern England are completely under ice, as is the North Sea. The Sahara Desert was humid. You can go into the middle of the Sahara Desert and you can see rock paintings that humans made there, where they're recording hippopotamuses and things like that, living in the middle of the Sahara, at this time. And we'll see in a minute that the major tropical forests shrank.



So this is more or less the global pattern. The grey now is ice. The green is tropical forest. The red and orange are--excuse me, the green is grassland; the orange is rainforest. So there are tropical forest refugia, in certain places.



And if you were to go into the south, what is now the South China Sea, which is currently covered by water, elephants and tigers could walk out, over that, because it was dry land--enough water had been tied up in the ice to drop the sea level down that much--and that is how they got to Borneo. So they could actually just move down from Asia and get out as far as Borneo, but they couldn't make it across Wallace's Line--there is a deep-water passage there that Alfred Russel Wallace documented in the biogeography of Indonesia--and they couldn't make it to Australia or New Guinea.



So the sea level has gone up and down, and that's changed continental margins and the ability of things to move around in them. So that's impact of glaciations. What about mass extinctions? There've been two biggies, end-Permian and end-Cretaceous. And at the end of the Permian not only did the trilobites disappear, but in fact the estimate is that 97% of all marine invertebrate species disappeared at the end of the Permian. That is an extremely close brush with sterilizing the planet; it came pretty close.



At the end of the Cretaceous the things that disappeared, that we probably would like to have around to look at, if we possibly could--ammonites, dinosaurs--almost everything that lived on land, that was bigger than five kilos, went extinct, and about 70% of the marine invertebrate species went extinct. So this was a big one, but the biggest was the Permian extinction.



So these are the trilobites. They had been around since the late-Cambrian--mid-Cambrian to late-Cambrian--so they had been around for about 250 million years, and they went extinct at the end of the Permian. And these are ammonites. In fact, the chambered nautilus is fairly close to being an ammonite; it would be sort of a modern survivor of this lineage. So they were squid-like creatures that had curved shells. And if we look at the diversity curve for--so this is the number of families that you could find; these are mostly marine invertebrate families. Okay? So the number of families of organisms. This scale goes from 0 up to about 1000.



This is the beginning of the Cambrian, right here. This is the Vendian, and then the Cambrian begins here. This is the Ordovician, the Silurian, Devonian, Carboniferous, Permian, Triassic, Jurassic, Cretaceous, Tertiary. So this is the Age of Dinosaurs here; this is the Age of Mammals here. And you can see that most of the last 550 million years of history is a history of marine invertebrates.



This is a mass extinction at the Ordovician. This is a mass extinction at the Devonian. This is the Permian mass extinction, and this is the Cretaceous mass extinction. The red is the modern fauna, the green is the Cambrian creatures, and the blue is the stuff that originated in the Paleozoic. So you can see that we still have--almost all the Cambrian things are gone. We still have families of things that originated in the Paleozoic, and what we think of as the modern creatures really started, some of them started way back in the Cambrian, but they built up a lot in the Carboniferous and Permian, and then radiated again in the Triassic.



So what caused that big extinction? Well Gondwana was breaking up, and so--Laurasia was also separating from Gondwana--so Pangaea was breaking up. At that time there was large-scale volcanism, and at that time there was a lack of oxygen in the oceans. If you go to the Black Sea today--the Black Sea is sort of the model for what this ocean looked like.



The top oh twenty meters or so of the Black Sea is oxygenated and has fish in it. The Black Sea at its deepest point is about two miles deep, and everything from twenty meters, down to the bottom of the ocean, is anoxic, and it stinks like rotten eggs. Okay? Imagine the entire world's ocean being in that state: a very thin, oxygenated, clear upper layer; and everything below it basically anoxic: no vertebrates can live in it; it's dominated by bacteria; and it stinks like rotten eggs.



Some people have suggested that there were extraterrestrial influences at the time. It's been difficult to find a meteorite crater of exactly the right age. It doesn't mean there aren't any--absence of evidence is not evidence of absence--but plate tectonics has remodeled the surface of the planet extensively since then, and it's quite possible that there was a big meteorite crater but it got subducted and it's been erased, so that we can't see it. At any rate, this is a fertile area for speculation, and people have thought of asteroids, comets and supernovas that might have affected the planet at the end of the Permian.



It seems likely that it's the breakup of the continents and large-scale volcanism, but I can't really claim that we really know what caused the extinction. If you go to Siberia, you can find what are called the Siberian traps. These are among the largest flood basalt lava flows on the planet, and they have just the right age; they're at about 251 million years.



And we know that the extinction lasted not too long; it was a few 10,000 years. It happened both on land and in the oceans, and the organisms that went out in the oceans were the ones that were particularly susceptible to changes in the gas regime. So that would suggest very high CO2 levels.



So one idea is this: there were massive volcanic outbreaks in Siberia. That caused global warming. That global warming then triggered the release of a huge amount of methane that was stored in the ocean. Okay? This is this Black Sea-like world ocean. The methane then gets oxidized to carbon dioxide, and essentially extinctions happen by poisoning and asphyxiation.



We do see a signature in the rocks that indicate that there was an amount of carbon that was oxidized at that point equal to several times the current biomass of the planet. So carbon levels really dropped. I didn't list it here, but I believe that at the end of this process the percentage of oxygen in the earth's atmosphere is about 7%. Well that's as though I took you suddenly in an elevator right to the top of Mount Everest; that's hard to deal with.



Okay, that's one of the more plausible hypotheses for the end-Permian extinction. The Cretaceous extinction is at just about 65 million years ago; slightly less, 63 and a half, 64 million years ago. And we do know that there was a big meteorite that hit the Yucatan right at the right time. It probably did trigger extinctions. Mechanisms aren't completely clear. It wasn't necessarily the sole cause. That meteorite in the Yucatan could have set off massive volcanism in India, and the reason is this:



The earth is a spherical lens, and if you throw a big rock into one side of the earth, the energy from the impact radiates out, reflects off the walls of the earth, and comes back together at a single point on the other side. That single point on the other side was focused into western India, at the time that India was moving across the Indian Ocean, before it hit Asia. It was just in the right spot, on the other side. And that's where those lava flows are, and those lava flows have exactly the right date. So there's some reason to think that this might actually have happened.



If you go to the Hindu and Buddhist cave temples of the Western Ghats in India, you will be in those lava flows. They are massively thick and they cover a huge area. So that's not demonstrated, but certainly the meteorite is well-documented.



It probably looked something like this. So this is about a 30 kilometer wide meteorite. It's coming in probably at about 100,000 miles an hour, and of course it completely fragments and sends up ejecta. And since it's hitting into a shallow sea, it sends up a large tsunami, a mega-tsunami. There is evidence in Texas and Oklahoma that the waves crossing the southern coast of the United States at that point were one to two kilometers high. So a big event; and burning debris rains down across the planet.



If you go to Mexico now, you can see the outer ring of the crater. It's a series of freshwater wells in the cracked limestone pavement of the Yucatan. If you look with geological probes under water, you can see the rim of the crater. This is a distance here of about 200 miles across. It's a big crater.



So this is Simon Conway Morris's reconstruction of what happens. Of course, when the rock falls on your head, everything's killed right there. There are giant earthquakes. Then within ten minutes, the rock falling out of the air ignites all of the forests of North America. About ten hours later tsunamis are pretty much covering the planet, taking out anything within one kilometer vertical distance of the ocean.



Probably the first extinctions of things that have a broad geographic range are occurring within a week. There's a very, very dusty atmosphere for about nine months, and that induces a nuclear winter that lasts about ten years. We know it probably didn't go on much more than ten years, because the plants do not notice this event. The animals get killed, but the plants have a seed bank in the soil, and the seeds can make it through. So the plants don't notice this event very much. Continental vegetation starts to recover.



The planet is pretty much covered with ferns for about 1000 years, but within 1000 years we start getting forests back and things like that. Then it takes the deep water in the ocean several thousand years to recover. It takes about 50 to 100,000 years for the oceans to become well oxygenated again.



It's thought that some populations of dinosaurs, some places in the world, managed to go on for about another 100,000 years, before they all died out, and that the ammonites, the last ammonites went out about 300,000 years later; and then you can see the rest of this going on. It took about 15 to 25 million years after the extinction to repopulate the planet to the level of biodiversity it had, before the meteorite hit; and that is an estimate of how long it might take the planet to recover from the current human caused mass extinction, which is going to be roughly an extinction of the same size as one caused by a meteorite.



This is just a bit of evidence. This is a section--I'm not going to run through all of this, I just wanted you to have this, if you wanted to, so you could see some of the evidence. This is a deep sea core off of the Florida Coast, and it marks the boundary between the Cretaceous and the Tertiary, and in this chunk of it right here are the impact ejecta; so there is basically glassy, tectite globules and things like that, and shocked quartz, in here.



And the iridium--the famous iridium anomaly--iridium is enriched in meteorites and poor on the earth's surface, and you pick up a lot of that element right in here. So this is the kind of evidence from around the world that indicates that this was a big event.



So that's the end-Cretaceous extinction, and it seems to be linked to the meteorite; and may not only have been caused by the meteorite, there were also volcanic eruptions. I'd now like to do a little bit of local catastrophe--this is on a more frequent timescale--just to convince you that sometimes, on a shorter time period, conditions are quite unusual.



So major earthquakes; I mean, we've all experienced, in 2006, the big tsunami in Indonesia. There's several of those per century. We haven't really had a volcanic eruption in our lifetimes that came anywhere close to Santorini or Tambora. Krakatoa was much smaller than Tambora; and these things caused tsunamis and global cooling.



Then there are the gigantic eruptions. Eruptions that were occurring in the Cascade Mountains during the Pliocene would do things like drop clouds of volcanic ash onto wandering herds of wooly rhinoceroses in Nebraska, 2000 miles away. And when the Phlegrean Fields at Naples went up, they dropped ash into Kiev, in Russia. The Phlegrean Fields are still active, and they're a rather heavily populated suburb of Naples right now. As a property owner, you have to kind of wonder what you're sitting on. These come fairly rarely, every 10,000 to 1000,000 years.



Then there are undersea landslides, and these can produce really huge tsunamis. So if the Nile Delta, or the Mississippi River Delta, or the Amazon Delta loses structural stability and sloughs off into deep water, dropping cubic kilometers of sediment at one go, you get a very big tsunami. I'll show you one in a minute. Okay? And then there are super floods, and we've had some of those in Eastern Washington. They've occurred in Siberia and Manitoba. They happen at the ends of Ice Ages, when the glaciers are melting.



So here is an example of a mega tsunami, and this is what happened when the West Coast of the Island of Hawaii fell into the water about 125,000 years ago. It dropped a chunk of rock that was probably about 20 kilometers wide, by about 1 or 2 kilometers deep, by about 8 kilometers high, onto the floor of the ocean, and by the time it had gotten this far, it was moving 500 kilometers per hour, and it shoved blocks of island that were about 1 kilometer long out into deep water, about 200 kilometers away. And that's just about the right velocity, in that depth of ocean, to entrain a tsunami.



And this is a geological model of how high this tsunami was. So the landslide is here, and then the tsunami goes out; it actually goes well up into the top of Lanai here. This is in meters. So when you start getting red, you are up at 1000 feet above sea level. The highest point of the run-up of this tsunami was right here at Ho'okena. It went up 2400 feet, according to that.



And there had been previous ones; other pieces of island had fallen off at various points. There is a ring of coral that goes up to about 1500 feet elevation, right here, from an earlier tsunami, and perched on top of the island of Lanai is a lake of sea water that was deposited on top of the island, by a mega tsunami. So sometimes the surf is really up. These are big waves.



This is a recent volcanic eruption, just to show you what it will do. This is pumping an awful lot of ash into the atmosphere. This is at 22 kilometers elevation, and this actually caused global cooling and beautiful sunsets for a couple of years.



And then these are the super floods of eastern Washington that went down the Columbia River, about a kilometer high, and took an awful lot of the soil of eastern Washington off. And that's what happened when a giant lake suddenly caused a glacial dam to burst and the flood went out. Okay? This is the kind of a boulder that could be easily moved by a flood that size.



So basically the idea of this lecture was to show you that life changed the planet, and mainly it was bacteria that did it; that the planet and the extraterrestrial environment have had occasional major impacts on life. This big picture view, this macroevolutionary view, describes a world that's really qualitatively different from our normal experience. And we're going to reconstruct what happened to some of those things next time in the fossil record.



[end of transcript]



 

The fossil record holds a lot of evolutionary information that can't be seen on shorter time scales, although the more recent fossil record is more complete. Among other things, the fossil record demonstrates that extinctions can open up ecological space for new speciation and radiation, and that life forms tend to begin small and evolve to be bigger over time.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 17

Transcript



February 25, 2009



Professor Stephen Stearns: Then today we're going to take our third look at the history of life on this planet, and it's going to be about the fossil record and the major groups of life. You remember, the first look was major transitions, and the issues involved in them. The second look was how life shaped the planet and how the planet shaped life; so it was a description of the geological theater in which evolution has occurred. And today we'll actually look at the fossil record, which has its own unique and important messages.



So I'm going to again give you another view of geological time. This is something that's important to build up in your head. It takes awhile. The names are unfamiliar, the depth of time is astonishing. But it's a very necessary framework for understanding evolution on this planet. We'll talk about a few big events, the major radiations, the groups that are still expanding, the ones that are vanishing or gone, vanishing communities, extraordinary extinct creatures. Then I'll mention stasis and I'll also mention Cope's law.



So here is another way of looking at geological time. Last time I showed you the 24-hour clock. This time I'm showing you a series of blowups, a three-panel blowup. So here is the origin of the planet. Here is today, up here. And the pre-Cambrian is in red.



So this is everything before the major animal groups and fossils with hard parts appear. And, as you can see, that's most of life. Roughly speaking, life begins here, and becomes eukaryotic somewhere around here, and multi-cellular somewhere around here, and we start picking fossils up at the beginning of the Cambrian, in any kind of numbers; there were a few before then.



And then if we take everything after the Cambrian--it's called the Phanerozoic; that's this column here--and we blow that up, and you can see it falls into the Paleozoic, the Mesozoic and the Cenozoic, with all of these eras in it. And some of these eras are actually marked, their endings are marked by mass extinctions, and the way that the geologists could tell, around the world, looking at different rocks that they were dealing with the same rocks, is that there are characteristic fossils found in them that disappeared all over the world at a certain time.



And so, for example, the disappearance--the trilobites appear in the Cambrian and they disappear at the end of the Permian. Any rock in the world that you see that has a trilobite in it is going to be in the Paleozoic. The ammonites, you'll see in a few minutes, appear and disappear a number of times, but they finally disappear at the end of the Cretaceous. Any rock in it that's got a complex ammonite in it is Mesozoic.



So these geological eras are actually, in part, defined by fossils, and the coordination of them across the planet is done by matching types of fossils. In the late twentieth century we had radiometric dating that helped a great deal with this, and that's gotten better and better. But the original layout was done with fossils. And if we then take everything that's happened since the end-Cretaceous mass extinction, that's called the Cenozoic. So this, the Mesozoic is more or less the Age of Reptiles; the Cenozoic is the Age of Mammals; and we blow the Cenozoic up, this is what we get. We get Paleocene, Eocene, Oligocene, Miocene, Pliocene, Pleistocene.



And the last 10,000 years is the Holocene; that's since the glaciers melted, that's the period we call the Holocene. And roughly speaking the world restocks itself with biodiversity in the Paleocene and Eocene. We have roughly modern levels of biodiversity since the Oligocene, in terms of mammal families and things like that. And most of the mammal orders have their roots in the Eocene and Paleocene; as you'll see in a bit.



Now if we look at large-scale events, one of the most interesting is well when did multi-cellular life really get going? And for that the tiny fossils that are preserved in phosphate beds in China are absolutely astonishing. These things have been discovered within the last ten years.



They come from a number of places in China, but this spot, Chengjiang, in Yunnan Province, is--I think it's on Yunnan; it might be just on the border with another province there; no province lines in the map--are certainly some of the earliest and most intriguing. So the Cambrian starts at about 550. So this is 20 million years before the Cambrian; we're in the Vendian, we're in the late-Proterozic Era. And a lake, or an inlet, dried up and the salts in it crystallized and they perfectly preserved the algae that were in it. So these are micrographs of microfossils showing multi-cellular algae, and in some of them you can even see the spindles in the mitotic divisions.



In formations in China of the same age, there are multi-cellular, bilateral animals. These look like early-stage cell divisions of Crustacea. So this is again 20 million years before the Cambrian, and the implication that there might be a Crustacean 20 million years before the Cambrian is a very interesting one, as you'll see in a minute.



So our molecular phylogenies suggest, looking not at the fossils but at the molecules, that the eukaryotic radiation--so that's before multi-cellularity; this is just the eukaryotic cells making Protista--that was underway about a billion years ago. These microfossils support the idea that many groups may have diverged before the Cambrian, but we have no trace of them in the fossils. We just have this marker; we have these Crustacean-like embryos.



Now if that's really true, then the first fossils of large animals, animals that you could see with the naked eye, that had hard body parts, that had endoskeletons or exoskeletons, these things crop up in the Cambrian, and they may simply then be recording the fact that formerly soft-bodied things started to acquire skeletons. So the groups existed before then, they just couldn't be fossilized, and that that may very well have been because of co-evolution with predators.



So that's the picture that seems to be emerging. I just want to remind you that the Tree of Life has these three big groups in it, and we're now going to blow up this part of it. Here we are.



The Chinese microfossils look like they're right about here, and they are at 570 million years ago. And if we just walk out around the Tree of Life, and say, "Oh, anything that has that branch length from what we think is the origin, was probably there at the same time, even though we don't have a fossil of it." That's the implication of the molecular phylogeny; it's that everything else that's about that far out from the common ancestor was probably there at the time. That means that all these other branches were there too.



Now most of these other things are single-celled organisms, and we wouldn't expect them to leave fossils. Okay? I mean, we've got stuff like slime molds and amoebas and euglenas, the ancestors of--let's see, where is malaria and stuff like that? We've got all kinds of algae out here. Those things were probably all there. We just don't have fossils of them. And that's why it's really important to be able to deal with both the molecular phylogenies and the fossils, because they complement each other and they allow a kind of inference that's not available from either alone.



Now, what happens in the Cambrian? That's when we really start- when the fossil record really gets going. The idea that there was an explosion of biodiversity in the Cambrian seems to be well supported by the fossils. Okay? This is the number of orders that can be observed, of animal groups. So these are fairly large clades of marine invertebrates that start--and some, by the way, by the end of the Cambrian, we start picking up vertebrates as well--and they start getting added on at a pretty high rate.



And the interesting thing is no major body plans appear in the fossil record, in animals, after that. They do in the plants, but in the animals it's as though there's one burst of diversity, 550 million years ago, and then all the major body plans get frozen, and we don't get new kinds of animals after that. That's kind of a puzzling and not completely solved problem. Why was it that way?



Now let's take a look at one of these communities. They contain some organisms that are profoundly weird. By the way, they weren't very big. The giant among them, the sperm whale of the Cambrian seas was this guy, up here. Okay? That's Anomalocaris, and that is an arthropod predator, arthropod-like predator, and it's got some funny sort of quasi-tentacle antennae, and a mouth right here, and it swims around, and it's the biggest, nastiest thing in the ocean, and it's about this big.



So if you are skin-diving in a Cambrian sea, you don't need to worry about white sharks. You are actually the biggest, meanest thing around. Okay? And that's an interesting observation. Again and again, in fossil history, things start small and get big. Things start small and have short generation times and short lives, and get to be big and have long generation times and long lives.



And I don't mean by that that the small things are replaced by the big things; the big things add onto them. It's like a community would be dominated initially by small things, and they would continue to be there, but big things would evolve. So this is that process starting to happen.



There are a few things that were running around, in these oceans, that we don't have anymore. There are trilobites here, of course. There is this profoundly puzzling creature. Okay? And we're going to--that's Opabinia--we're going to take a good look at it, in a few minutes. That's one of the favorite animals of Derek Briggs, who's now the director of the Peabody Museum. Derek, by the way, has great BBC cartoons of the way these things swam and moved. He's done the functional morphology of the Cambrian community. So if you're interested in that, maybe you could talk Derek into having a showing. So that is something that's not around anymore. But something like this is.



That's a priapulid worm, and there are still priapulid worms that look pretty much like that. So that thing is now a living fossil. And here's an Onychophoran, and Onychophorans that look just like that are running around the Australian rainforests now; instead of living on reefs, they're running around the rainforest, but they look pretty much like that. Okay?



So the things that we get in the Cambrian are at least three of the mollusk classes. So these are the chitons, these are the snails, and these are the squids, octopuses and ammonites. We get the polychaetes, which are the biggest group of the annelids--the ones that are most familiar to you are probably earthworms; those are oligochaetes. But the polychaetes--I think there are 43 families of polychaetes. They're a very dominant group in the ocean, and have been for 550 million years.



We start getting arthropods; so we get the trilobites. The chelicerates are the horseshoe crabs and the spiders and their relatives, and we start picking up some Crustacea. We get the brachiopods, the lampshells, which are still around. If you go diving on a reef in Malaysia, you can see brachiopods. There are deep-water brachiopods around the world, but they've mostly been in retreat for a long time.



And we get echinoderms, and the fact that we get echinoderms is interesting because they're the sister group of the chordates, and that implies that the chordates had diverged from the echinoderms, at that point, and they just weren't fossilizing. And we know, from the first fossils that we can get of things like Amphioxus, that if you have a tiny, little, one-inch long, translucent, tadpole-like, fish-like chordate, that's the ancestor of the vertebrates, it's probably not going to fossilize. So our best evidence that that divergence had occurred is the existence of the echinoderms.



And by the way, the echinoderms went through an explosive radiation. They made many classes. The different classes of the echinoderms now are things like the asteroids, which are the starfish; the holothuroids, which are the sea cucumbers, and so forth. There are, I think, six or seven classes currently of echinoderms; but back in the Cambrian there were about twenty-five or thirty. Most of them have now gone extinct. And some of those things that you saw in that earlier picture were extinct classes of echinoderms.



Okay, so for the animals there's this explosion 550 to 500 million years ago in the Cambrian. It's very different for the plants. The plants had a much steadier, more measured evolution of diversity. Okay? The major groups of plants arrive later because plants got onto land later. Most of the animal groups, all the animal groups originated in the ocean, but much of plant diversity originated on land; so they had to get onto land.



The mosses and the ferns appear in the fossil record in the Devonian, about 400 million years ago. The gymnosperms, which is pines and firs and their relatives, they actually are 350-million-years-old. So they appear in the early Carboniferous, and they undergo continuing evolution up to the present day. So they keep getting- diversifying and becoming more sophisticated. But there are recognizable gymnosperms 350 million years ago.



And when the flowering plants evolve depends on whether you're looking at molecules or fossils. The molecules suggest that it might be as old as Carboniferous-Permian-Triassic; that is, 200 to 300 million years ago. Some people don't believe that. The really solid evidence, of course, is the fossil, at a certain age, and that's in the late-Cretaceous. So you can see angiosperms that are 75-million-years-old in the fossil record.



This is what the first plant on land might have looked like, and the first plant on land might actually have been a liverwort. So this is a thalloid liverwort. And when you look at it, it looks a fair amount like algae that we are familiar with and that we see in the intertidal zone. It doesn't really look that different in its structure from a marine alga, but it is adapted for living on land.



And to get onto land this is what you need. If you're an animal, you're going to have to come up with an impermeable skin. If you want to locomote on land, you'll need limbs, and for that you'll need shoulder and hip supports. And if you want to reproduce on land, rather than in the water--which is, of course, what many of the amphibians have continued to do--then you'll need an egg that won't dry out. So you need a shell and an amnion, and this basically is something that happened between the amphibians, and then everything that came later in the tetrapods.



If you're a plant, you need an impermeable leaf. That means you need to invent the biochemistry and the developmental biology to make a waxy cuticle. You need a means of gas exchange. So you're going to have to invent all of the neat stuff about stomata and stomatal regulation of carbon dioxide coming in and oxygen going out. And you'll need to have roots, resistant spores; eventually you'll need seeds. So there's really quite a bit of stuff to evolve, when you come onto land. This is a major event. It was complicated and it took some time.



If we look at the vertebrates coming onto land, here are some late-Devonian lobe-fin fish. So the group that seems to have spawned the tetrapods is related to the Coelacanths, the lobe-fin fishes. I'll show you a picture of Eustenopteron and Ichthyostega in a moment. And these things start--this creature, Eustenopteron, is actually a pelagic fish. It's not really crawling around in the drying up lagoon; it appears to be swimming in open water.



But, as you'll see in a minute, it has really pretty good beginnings of the tetrapod limb. So it looks like some of the structural elements in the skeleton, that were needed for things to come on land, probably developed for other reasons, in another environment, as an exaptation, something that happened for other reasons earlier in evolution, and that could then be co-opted and used to get onto land. And these are some of the relatives. Okay?



So you can see Coelacanths in the fossil record at 360 million years, and you can see them from a submersible off Madagascar today. They're a nice living fossil. Here's Eustenopteron. The skeletons are recovered from Miguasha in Quebec; 385-million-years-old. It was a pelagic fish, and you can see that it already is getting, in its hind limbs, many of the identifiable elements of a vertebrate limb.



So this is a blowup of the pectoral of Eustenopteron. It appears to have a humerus. This is Ichthyostega. This thing is a transition form between fish and amphibia. It's late-Devonian; it's 20 million years later. These usually come from eastern Greenland; that's where the fossil deposits are. And this guy already has most of the elements of the vertebrate limb.



So this developed in a swimming environment. This guy arguably was crawling around in shallow water, but he can't support himself as an adult. That shoulder girdle and the hip girdle are not strong enough for that animal to actually walk on land, if it's an adult. The larvae could.



So perhaps the first stage of coming onto land was the kids went exploring, and then they went back in the water and grew up to be adults. The parents couldn't go into the new habitat because they didn't have limbs that were strong enough to support them. I think that's kind of a cool idea. So it might have been that, just like with computers, the young were showing the old which way was up.



If we look at the plant radiation, there's a whole series of acquisitions of major elements of what it means to be a plant, and they occur at a pretty steady pace between about 450 and 75 million years ago. So chlorophyll B is quite old. I would guess that chlorophyll B is on the order of maybe 1 to 1.5 billion years old. You get plant cell structure probably at the level of about a billion years. You get alternation of generations, haploid/diploid generations, coming in pretty early.



Then you have, as you move out of the mosses, and move towards the club mosses, you can see that the water delivery system, of plants, starts to develop. So they're developing roots and they're developing all of the plumbing that will allow water to move and bring nutrients from the roots up into a growing structure.



Wood starts to develop right about in here, and by the time you get up into the Equisitifolia and the precursors to the gymnosperms, you're getting pretty well developed xylem; so you're getting phloem, complex xylem, and a pretty good delivery system. Then the seeds evolved with the gymnosperms; gymnosperm means naked seed.



And this is the radiation here of the gymnosperms. The Pinales would be the pine trees, and firs, and all of that. And the Gingkoes, of course, are the familiar Gingko trees; there's one down here at the corner of the Peabody Museum. And that makes a clade. And that's where seeds were invented.



Then as we go up further, we get into pollen grains that have a distal aperture, and then finally we get to the flowering plants. And at the base of the angiosperms, down here, there are some wonderful and weird plants, and the only one that I'd really like to mention now, time permitting, is Welwitschia, which is the Gnetales.



And Welwitschia is a plant that basically is a root with two leaves, and the two leaves can grow to be up to 100 or 200 feet long. It lives in the sand dunes of Namibia, and because sand drifts and makes dunes that grow, Welwitschia can keep growing to keep its leaves on top of the dunes. And so some Welwitschias are actually 100 or 200 feet high; it's just that they're all below ground and they just have these big leaves that come out the top. So there are wonderful things that are represented in the plant radiation.



Okay, so the theme of that basically--let me just go back and reinforce these two points. Some of the stuff that you need to get on land was developed earlier in the water, for other reasons, and then was co-opted to get you on land, and that's what probably happened with the vertebrate limb. The plants developed much of their diversity after they had gotten onto land. And you can see that they are adding things like vascular canals and water delivery systems and things like that--wood--at a fairly steady pace, as you go up through a period between about 450 and 75 million years ago.



If we then look at large patterns in the history of life, to see what kinds of messages the fossils give us, this is one of the classical ones. This is how many different families of ammonites there were. Okay? And you can think of each of these radiations, that are presented as kind of a leaf with grey coloring around it, as being roughly at the level of an order.



So an order of mammals would be--to make it familiar to you--would be something like the ungulates. An order of birds would be something like the albatrosses and their relatives. Fairly big groups with a lot of species in them. And within each of these groups you can see that there are lots of families.



Now look what happens to them. At the end of the--they start to radiate, back in the Devonian--at the end of the Devonian there's a mass extinction, lots of them get cut off, two lineages come through. This lineage radiates, makes a whole lot of different species and families of ammonites. At the end of the Permian, they all go extinct.



This line here manages to get two of them through--two lineages, maybe three--through the Permian mass extinction. One of them goes out in the Triassic; the other radiates. At the end of the Triassic there's a mass extinction. Almost all the ammonites disappear again. One or two lineages get through, into the Jurassic, and at the end of the Cretaceous these two surviving branches both go extinct.



So people looked at that, and what they saw was this continuing extinction, and then re-radiation, and extinction, and re-radiation, and they asked themselves, "Can the world hold only so many kinds of ammonites? Does it kind of fill up, and then when it's wiped clean, does that create a space for the others to re-radiate?" Well the pattern is consistent with that interpretation. Consistency is a very weak logical criterion; but it's evocative. So I leave it at that.



Now that consistency comment's going to apply to this as well. So this is the mammal radiation. Okay? And when you look at it, the first thing you notice is oh, mammals started to radiate back in the Triassic. If we were back in the Triassic we might not have called them mammals yet, but they have already split off from other ancestors, and it looks like things like the Monotremes have their roots at about that level in time. So we're looking back about 200 million years.



During the whole time that dinosaurs were the dominant large creatures on the planet, and the most diverse tetrapods, the mammals continued to radiate. There were multituberculates, there were triconodonts; there were all sorts of things, back there. They tended to be rather small, but they were perking along. Then there's the end-Cretaceous extinction. Everything bigger than five kilos that lives on land gets wiped out, and the mammals then radiate.



Well that is consistent with the idea that the extinction of the dinosaurs was a necessary pre-condition for the radiation of the mammals. And it looks like a reiteration of the pattern we saw with the ammonites: clean the planet out and make space, and then they can evolve again. So this is really kind of a tetrapod recapitulation of what we saw with the ammonites. But, as I said, consistency is a weak logical criterion, and the problem is we're dealing with one planet, and we don't have replicates. [Laughs]



It would be nice if we could replicate this experiment a hundred times and see that every time the dinosaurs went extinct, the mammals radiated. Okay? We have a sample size of one. So it's a very interesting pattern. It might very well be true. It sounds plausible, and you can't demonstrate it experimentally.



So what are the groups that are still radiating? If we just look around the planet right now, what do we see? Well the beetles are still going like gangbusters. We don't actually know how many beetles there are. The number of beetles that have been named is I think about 350,000. The number of beetle species that might exist could be on the order of 5,000,000.



When J.B.S. Haldane, who was an atheist Communist, was having dinner with the wife of the Archbishop of Canterbury, she asked him, "Mr. Haldane, what do you conclude about the nature of the creator from your study of biology?" And he turned to her and said, "Madame, an inordinate fondness of beetles." [Laughter] So there are a lot of beetles, and they're still radiating.



The Diptera, the flies and the mosquitoes, are a young group, and they are still producing new species. Among the mammals, it's the bats that are probably the most impressive producers of biodiversity, along with the rodents. And the place where the bats and the rodents are doing the most of this is in South America.



So if you really are a mammalogist, and you want to study recent evolution and see things that are still in the process of speciating, South America is certainly one good place, and the groups to look at are bats and rodents.



In the flowering plants, there is really impressive biodiversity in the composites, the orchids and the grasses. There are about 12,000 species of orchids I think. And I have forgotten--Jeremy, do you know the figures for the grasses?



Teaching Assistant: Yes. I think there's somewhere around 15,000.



Professor Stephen Stearns: 15,000 species of grasses and composites.



Teaching Assistant: There's around 30,000.



Professor Stephen Stearns: There are about 30,000, and they probably don't even call them composites anymore.



Teaching Assistant: No.



Professor Stephen Stearns: What are they called?



Teaching Assistant: Asteraceae.



Professor Stephen Stearns: They're called Asteraceae. Okay, see, the phylogeneticists are busy, they're on their game, they're naming stuff. Now that's---those are the clades that are currently filling the world with life.



What about the stuff that's been wiped out? Well all of those exotic things in the Burgess Shale, they're gone forever, and they've been gone for hundreds of millions of years. The trilobites, the ammonites, the dinosaurs, those are all gone. There was a wonderful group called the glossopterids. They were Jurassic tongue-ferns; they were ferns that looked tongue-like.



There's a great story about how when South America got connected to North America, at the Isthmus of Panama, about 10 million years ago, a bunch of tough, North American hoodlums migrated south, over the Isthmus, and ate up everything in South America.



They were called things like pumas and wolves and stuff like that, and they ate up the South American notoungulates. There were a few things that came north; possums, armadillos came north, but most of it was a movement south. And so there was a complex Miocene and Pliocene fossil fauna in South America that's vanished forever.



In the last 10,000 years, mostly on islands in the Pacific, 25 to 35% of the world's birds have gone extinct. And outside of Africa, most of the Pleistocene megafauna is gone. If you want to see what the Pleistocene looked like, go to a national park in Africa, because that's what North America looked like 10,000 years ago, when we had 300, 400-pound beavers; and there was a North American lion that was bigger than an African lion; and of course the mammoths and the wooly rhinos and all of those things. So we are actually missing a lot of this stuff.



And, on the one hand, none of us probably ever woke up in the middle of the night, in a cold sweat, worrying about the fact that the dinosaurs were extinct and we couldn't see them anymore. And some ornithologists, who know about the recent history of extinction in the world's birds, probably do occasionally wake up in a cold sweat at two o'clock in the morning and worry that they were gone.



But most of this stuff, we regard that as oh, it's in the drawers of the Peabody Museum; it's old, dusty fossils. But basically what we're talking about here is vanished worlds; vanished complete communities, vanished profligate, extravagant radiations that produced life, that filled up the planet, and then disappeared. And 99% of it's gone; we see a very small fraction that remains. And that's actually just a fact of life. Okay? It doesn't actually necessarily call for an emotional response, other than the observation that hey, that's what happens.



Now let's go back to one of those places. This is a vanished community, this is the Burgess Shale, and about 500 million years ago--the Burgess Shale is about 505 million years old, so it's sort of late-Cambrian. At that point--this is the North American craton here; so looking at its western edge, it's eastern edge would be Quebec, and then this would be northern Canada, up here. This is the western edge. At that point it's slightly south of the equator. It's not connected to South America or to Asia, at that point.



This is where it is today. You're up at about 10,000 feet; you're about two kilometers above sea level; maybe 8000 feet. This is a geologist, and this is a fossil from the Burgess Shale. That one happens to look like a trilobite. Okay? And this is the shale here.



So at this site, 505 million years ago, on the western edge of the continent, there was a shallow water community that was living on the edge of a cliff, and occasionally the cliff would fall down, the sediment on the cliff would fall down, and it would bury things; and that's what the shale consists of. You're looking basically at a landslide that buried a lot of stuff.



And these are the kinds of things that it buried. So here is our priapulid. Here is Opabinia. Here is Anomolocaris; it looks like a huge looming predator in that shot; but remember, the biggest thing in the ocean was that big, and that's this guy right here. Here's one cruising in the background.



And these are some of the creatures that you can pull out of that shale. This is one of the most abundant. This is Marella. This is a primitive arthropod. Now remember the HOX genes, remember how to turn an onychophoran into a fly? Well this is an intermediate step. Basically you take a worm and you start specifying that the forward segments are going to form a head.



So you get cephalization. You can see that it's putting out gills and legs on most of its segments--but it's kind of stopping to do that on its back segments--and it's developed a hard exoskeleton. So this is steps on the way to becoming an arthropod. And we actually don't know whether this thing is the ancestor of Crustaceans or of the chelicerates or the trilobites. It's just an intermediate form between a worm and an arthropod. This thing is just totally bizarre.



This is Opabinia. Okay? And when it was first reconstructed, it resulted in hilarity; nobody could believe it. And the thing that really gets people about it is that it has five eyes, and it's got this proboscis that's got kind of a grasping organ out on the end of it. So it looks sort of like a cross between a spider and a vacuum cleaner. It's probably about this big. Okay? It's about one or two inches long.



And people just couldn't figure out where Opabinia fits. So Derek Briggs has made the study of Opabinia one of his projects; he knows a lot about it. And it appears to be related to Crustacea. But again you can see that it looks like it's intermediate between a worm and something else. So it's probably some kind of intermediate form, prior to the arthropods.



Now before I go on to stasis and Cope's rule, I just want to comment a little bit on what it means that entire communities have completely vanished. It really places a very relative view on the current world. When the Atlantic was opening--and the Connecticut River Valley might have been the Atlantic, or it could've been a river valley on a continent; it was a rift valley at that time--there were a series of rift valley lakes that stretched across eastern North America. They run basically from Pennsylvania up to about Vermont. And they opened and closed, and opened and closed several times.



Every time one of those lakes opened, the fish in them went through a big adaptive radiation, like the ammonites did, and then the lake closed and all the fish died off, and then it opened up again and another radiation of fish went on in it, and it closed up; and this happened again and again and again, both spatially and temporally, across the eastern United States, about 200 million years ago.



We're currently in the middle of a big anthropogenic extinction crisis, but it appears like this isn't something that the planet hasn't experienced before. Geological processes have caused many extinctions of entire communities, wiped them completely off the face of the earth, and life has re-generated new ones again and again and again and again. So that was one of the messages I'm hoping that you're getting from the fossil record.



Now what about stasis? What about the fact that the Coelacanth that you catch off the Comoro Islands today, looks almost exactly like the Coelacanth that's in the fossil record from 360 million years ago? What about the fact that the Onychophorans that you collect in Australia today are practically indistinguishable from the ones that you see in the Burgess Shale 505 million years ago? Why is there stasis?



And I mention this because if you were to write down a list of the big intellectual problems that are posed by fossils, this is certainly going to be on everybody's list. There are others, but this is going to be a prominent one. And this is something that was called to the attention of the world's scientific community, primarily by Steve Gould. This is one of the take-home messages of his life.



So stasis basically describes a long period with no morphological change. There's no apparent response to selection. Evolution doesn't appear to be going on. And it is puzzling, because we know that every nucleotide sequence undergoes mutations.



There is no way that you can stop the production of genetic diversity in these organisms. Okay? So for 350 million years Coelacanths don't change, but probably every nucleotide in their genome has mutated, over that period of time. So there's been opportunity for change, but they have not changed.



The examples of this include club mosses and liverworts, lungfish, Coelacanths, the priapulids and phoronids. You saw the priapulids--I pointed them out in the Cambrian- in the Burgess Shale shot--tuataras currently still existing on an island off New Zealand, and onychophorans; there are others.



So here are a couple of onychophorans. They're kind of intermediate between annelids and arthropods; velvet worms. And here are two possible explanations for stasis. There may very well be others, but I want you to have at least these two general ones in your toolkit.



And one is basically a selectionist explanation for stasis. It says that most of the things that we're talking about have some method where either a larva or a seed can find the environment in which the adult will do well. And so there is a selection of an environment, early in life, and that actually then selects the selection pressures that will operate on the adults. We see the adults, we don't see the larvae.



Basically the larvae have been wandering around the planet, searching out the environment in which the adults will grow up, for hundreds of millions of years; and we know that marine larvae are extremely good at this. The Coelacanths, we know that they're deep-sea creatures; they live down at about 600 to 1000 feet. That's a fairly stable environment. The club mosses, that's a little harder to see how this would work. But at any rate, this is one option. Okay?



So this is one of our alternative hypotheses. The reason things stay the same is that young life history stages find the environment in which adult selection will take place, and adult selection is stabilizing. Intermediate values are selected for. Things don't change.



On the other hand, there's a contrasting hypothesis, which is an internalist explanation. Basically it is that tradeoffs are creating the stabilizing selection--that's one possibility--so that instead of having an ecological explanation for why there's a long period of stabilizing selection, we have an internal physiological or developmental explanation of why selection has been stabilizing.



But there's another part, another option in the internalist explanation, and that is that early on, both in evolution and early on in development, key traits get fixed; key things get set up. The development of the eye depends upon the relationship of two tissue layers, so that there will always ever thereafter be nerves and blood vessels in front of the retina. Okay?



So if those things are laid down early, both in evolution and then in development, occur early in development, there's kind of an embedding. That means things have been in place that can't be changed without destroying normal development.



Now there are arguments for and against all of these things. You can find early developmental traits that have undergone a lot of evolution without destroying the adult form. So there are some real issues with trying to understand the mechanics of how this would work; and we don't know yet. Okay? I'm just giving you a few ideas that bear on the issue.



The other major take-home message is--that I've already signaled as Cope's Law. And again, there are two options here. One is that the reason that we see bigger things is that there's just a neutral evolution. Adaptive radiations have been creating little things and big things. But there was more room on the upper end than there was on the lower end; therefore even though it's been random, we see an accumulation of larger things, just because the upper limits are far away. Okay?



The lower limit on body size is always nearby; it's one cell, you don't get smaller than one cell. But the upper limit appears to be redwood trees and blue whales, and at least at the outset that's pretty far away. That's up at about 100 meters, for redwood trees, and about 30 meters for blue whales. So that's one possibility.



The other is that the reason that things got bigger is co-evolutionary. Co-evolution is shaping prey to escape and predators to kill, and prey can escape predators by getting too big to eat, and predators can kill big prey by getting bigger than they are. So this would be an adaptive life history hypothesis, saying that Cope's law results from a co-evolutionary arms race between predator and prey.



And we don't really yet have a powerful method for disentangling these two effects. And I think if you look at their logic, you can see that they're not mutually exclusive; they can both be going on at the same time.



Okay, so what does the fossil record tell us? It shows us a lot of stuff that we couldn't see at shorter time scales. We see a lot more detail in the recent than in the distant past. It looks like mass extinctions may open up ecological space, for the radiation of surviving groups. So it may be that you need an extinction before you can have a big radiation.



Most things start small and get big. And there's a lot of stuff that's not on the planet at all anymore; there are no surviving descendants. So the fossil record has a take-home point, that's actually a puzzle that can be attacked experimentally, in part by people doing evolutionary developmental biology and phylogenetics, and that is, why is there stasis? It's common, and we don't have an explanation for it.



[end of transcript]



 

Coevolution happens at many levels, not just the level of species. Organelles such as mitochondria and chloroplasts serve as good intracellular examples. Other living things make up a crucial component of an organism's environment. Coevolution can occur in helpful ways (symbiosis) and in harmful ways (parasitism). Many factors can influence coevolution, such the frequency and degree of interaction.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 18

Transcript



February 27, 2009



Professor Stephen Stearns: Welcome Orgo survivors, and others. I stuck this slide up, sort of outside the framework of the regular lecture, and I did so just to indicate that if you go through the scientific literature, you can probably find a neat case of coevolution, with some kind of beautiful biology in it, coming out every week. This one came out last week.



This is a Proboscis fly that lives in South Africa, and it pollinates flowers. And you can see that it has evolved a very long proboscis, and the flower has evolved a very long nectary, and it looks, in fact, very much like Darwin's orchid, and that moth called Praedicta, that Darwin predicted would have a long proboscis. But this is a fly. This is not at all closely related to moths, and that flower is not at all closely related to orchids. So this is convergent evolution.



And I think you'll remember, in reading the book, that there was a neat alternative hypothesis posed in the book saying, "Hey, it wasn't about the coevolution of the flower and the moth. There's a spider that sits on the orchid, and when the moth flies in, the spider tries to eat the moth; and so the moth kind of evolved a long proboscis so that it wouldn't touch that flower with anything but a ten-foot pole. Okay? So that was an alternative hypothesis, and there's actually some evidence for that in the case of the orchid on Madagascar.



But in the case of this interaction, which is in Cape Province in South Africa, with a fly and something that is not at all an orchid, the data indicate that, in fact, a coevolutionary story works just fine; and that looks to be what's going on. The longer the nectary, the more likely the pollination; the longer the proboscis, the greater the energetic reward--and the two things feed back and forth to each other.



So this indicates actually that Darwin's original idea was probably correct. And I would note that in the case of the orchid on Madagascar, the fact that there's a spider doesn't really mean that Darwin was wrong in generating his story, it just means that there is also something else going on.



Okay, so. We spent the first part of the course talking about microevolution. We spent the second part of the course talking about macroevolution. And today and Monday, we're going to talk about coevolution and evolutionary medicine as two areas in which micro and macroevolution interact in generating explanations of things.



And I think that you'll probably see, if you think about it, that in almost any reasonably complicated or large-scale biological pattern, both things have been involved; both micro and macroevolution. There's been some things that have been changing slowly and some things that have been changing quickly.



Now the tight genetic definition of coevolution is this. In one species you have a change in a gene, and that--excuse me for missing this; I was doing proofreading this morning; there should be 't' there--it stimulates an evolutionary change in a gene in the other species, and that change in the other species stimulates another change in the first species; so that you have kind of a gene for gene succession in time. One thing happens here; that stimulates something here; that stimulates something here.



That is the tight genetic definition of coevolution. If you could demonstrate that, I think everybody would agree, hey, you nailed it, it's really there. It's hard to do. The reason it's hard to do is that we don't normally know what the genes are that involved. We can see the phenotype, but we have difficulty inferring the genes. There are some cases of this that are well documented in rusts, rust fungi inhabiting wheat; Ustilago hordii is one of them. So, you know, pathogens of crop plants are things where this kind of coevolution is well documented.



Another kind of coevolution is phylogenetic. So you use tree thinking to try to infer what's been going on. And you look at closely interacting organisms--pathogens, parasites, pollinators, things like that--and you see if the trees can be laid right on top of each other.



Or, if you have one group over here--so you have, say, the pathogens over here and you have the hosts over here--you see if the trees line up and touch each other at the tips. That would indicate--without any crosses, so you don't see any lines kind of crossing over when you line them up--that would mean that the trees have exactly the same topology, and that every time the host speciated, the pathogen speciated. And if you see crossing lines, it means that a pathogen has jumped from one host to another. So that kind of approach gives you another definition of coevolution, and another tool for trying to infer it.



Now before I get into coevolution proper, I want to talk a little bit about co-adaptation, because co-adaptation actually contains within it a message that's of general significance for coevolution. Right at the beginning of life, the first replicators had to co-adapt in order to generate say a well-functioning hypercycle; they had to co-adapt to each other. And at the level of the cell, when you're looking at key molecules in the cell, all these interactions have co-adapted to each other.



So, for example, the ribosome here is in green, and you've got the mRNA coming into it like a ribbon, and you've got--the transfer RNA is pulling in the amino acids out at their tips, into the reaction center of the ribosome. And that brings the amino acids into close juxtaposition where an enzyme can operate on them to join them, and then clip them off of the incoming tRNAs, which then go on out, back into the cell to do their job again, and the protein grows out here.



Well, this is a rough sketch of the structure of the ribosome. It's actually more complicated than that, and it has really a beautifully sculpted reaction center in the middle of it. And the message from this is that every single important biochemical step and morphological structure inside the cell is tightly co-adapted, so that form matches function, throughout the cell.



And the reason that's the case is that these things are processing reactions that happen thousands of times a second, and that therefore accumulate to have big effects over the lifetime of the organism. If you've got something in you that is going to happen say 50 billion times in your lifetime, and you get a very, very tiny, 1/1000th of 1% change in it, that then accumulates 50 billion times, you have a massive result at the end of your life. So that things that are happening down at that level are driven by high frequency interactions. And the frequency with which things interact is one of the key elements of coevolution, in general.



If you look at a slightly higher level in the cell, you can find co-adaptation going on again. The axons that run into nerve fibers have different lengths, so that the signal coming from the brain will arrive at things that need to be coordinated at the same time. The muscles in electric eels have been turned into storage batteries, and the axons that run from the brain have had their lengths modified, so that they hit the different cells in the storage battery at exactly the same instance, so that the electrical charge goes out, all at the same time.



A four- or five-foot electric eel can kill a horse; that's how much electricity they can store up. But they can only do it because it's released exactly at the same time. If it dribbled out, it wouldn't take the horse down; or the naturalist exploring the shallow river in South America. Right?



Same kind of thing in your brain. There's very tight co-adaptation between your retina and its projections into the visual cortex at the back of your brain. So these connections have been sculpted by evolution so that the re-creation of the external world, in your head, is precise. And this has gone on in every organ of your body in one way or another. So the integration of the organism is achieved by co-adaptation of its parts.



That's not precisely the gene for gene kind of interaction between species, that people think about in coevolution, but it is a gene for gene interaction in the determination of those organ systems. A gene changes over here, and another gene has to change over there. It's just that the process is going on inside a single genome, rather than in two different genomes.



So that's not normally what biologists mean by coevolution. It usually refers to the mutual adjustment of the genomes of separate species. And that's kind of arbitrary I think, and the reason I think it's arbitrary is that we now conceive of the organism as kind of a babushka doll of nested levels of hierarchies that have been assembled over the course of the evolution of life, and that things that we now see as being integrated organisms, earlier, were independently evolving systems, and at that point the coevolution, that we now see as co-adaptation, was actually coevolution sensu strictu.



So I'm now going to talk about some intercellular symbioses. And the reason I picked intercellular symbioses as the first example of real coevolution is that these things are very intimate coevolutionary interactions. And you can see that in mitochondria and chloroplasts of course.



Then there's this wonderful and interesting critter called Wolbachia, that does lots of things to arthropods. The whole issue of the symbiosis of algae in reef building corals contains a lot of beautiful biology, and some interesting puzzles. And in all of these cases the interacting parts are really closely connected. Okay? So there's been a lot of evolution at the level of intercellular metabolism.



And I think that these tight symbioses are really major transitions in the process of being born. So one of the issues in a major transition is whether or not you have a change in the pattern of genetic transmission. And in these cases independent genomes are getting aligned, and in the extreme case of mitochondria or chloroplasts, they actually have the same pattern of transmission as the maternal nuclear genomes, of the host. Okay? So previously independent things are being integrated.



Conflicts are being at least partially resolved; although there are traces of these conflicts--as I told you earlier, there are mitochondrial cancers; mitochondria do occasionally get out of control. And there are things like the petite mutation in yeast, which is a mitochondrial issue. And then this new more or less well integrated unit has a performance.



That performance can vary among units, and therefore natural selection is starting to act on the new unit. So at the formation of the eukaryotes, when the mitochondria came in, you had a new unit, and then it was going to perform with respect to other such units, depending on how well the mitochondria were adapted to the nuclear genome; and that's a coevolutionary process.



Okay, so with mitochondria you've got all kinds of communication and coordination going on. The cell membrane of the previously independent purple sulfur bacterium, out here, now has within it an inner membrane that has got all kinds of biochemical machinery on its surface.



And this is where the citric acid cycle takes place, where electrons go down the electron transport chain, making ATP, and in the process letting a few protons leak out into the cytoplasm, which cause oxidative damage. So if you are worried about eating your blueberries and drinking your pomegranate juice, it is because mitochondria leak protons and basically create hydrogen peroxide in your cytoplasm, and hydrogen peroxide is highly oxidative and can do damage in the cell; and there's lots of kinds of repair machinery to deal with that.



This process here of exporting energy to the cell and getting information and substrate into the mitochondrion is a tightly coordinated one, and there have been lots of modifications to the mitochondrial membrane to make it an appropriate filter for the transport of goods, in and out. So it's been heavily modified by coevolution.



Now, Wolbachia. Wolbachia are very cool bacteria. They're cytoplasmic parasites. They live in the cytoplasm of arthropods. So they occur in insects and crustacea. They sometimes occur in nematodes. They seem to be able to get into things, generally speaking, in that large chunk of the tree, which is called the ecdysozoa.



And if you just think about the interests of the Wolbachia, it can only get into the next generation if it is in a female, because it is transmitted, like other cytoplasmic organelles, only through eggs and not through sperm.



Now this creates some issues for Wolbachia, because if they end up in a male, they're dead. So they have evolved some interesting ways out of that. They can induce parthenogenesis, in some species. So they will take that female and they will make her asexual, and then she makes only female babies.



So they get into the eggs of all of them. They can feminize male hosts, in pill bugs--so Armadillidium, the little pill bug that you can find turning over logs--it's an isopod and a crustacean--and when Wolbachia gets into Armadillidium, basically it takes males, and it has developed a method of interfering with its sex determination process and development, so that anything that's got a Wolbachia in it will grow up to be a female.



Now, as Wolbachia--and by the way, this creates a huge reproductive advantage for those females, and they start to spread through the population. They're not suffering the twofold cost of sex. They're only making female children. They spread, and they take over the population. And then, because there aren't any males in the population, and it's still a sexual species, Armadillidium goes locally extinct; being driven to extinction by the selfish cytoplasmic parasite that it has.



And the response of some, but not all, Armadillidium populations has been clever. They have cut out the sex determining part of the bacterial chromosome and put it into their nucleus and spliced it onto one of their own chromosomes, so that there is now vertical transmission of that selfish, sex-determining element. They don't really care very much about the rest of the bacterial genome that's been causing all this problem.



The only thing that's really critical is that they got the sex determining part out, and they spliced it into their nuclear genome, through a process that we don't really understand. All we can see is that we can observe, in some populations, that today that's the case.



This means that the conflict has been removed, at least for that sex-determining element, because now it's being vertically transmitted through both the male and female line, because it's in a nucleus. So the conflict disappears, and a 50:50 sex ratio is re-established; well after awhile, because now there's a new sex chromosome. Okay?



So now you have three sex chromosomes, rather than two, for awhile, and so there's a bit of chaos in sex ratios. And then that stabilizes; you get back to 50:50 sex ratios. And then it gets infected by Wolbachia, and the whole thing starts over again. And in some cases you can take the genome of a Armadillidium pill bug, and sequence it, and you can find four or five fossilized, sex determining chunks of DNA, that have been stuck into it. So there's an interesting coevolutionary process going on there.



In fruit flies and drosophila, they cause reproductive isolation, and they do that by cytoplasmic incompatibility. That means that a fruit fly is only going to be able to have offspring, if it's mating with a Wolbachia infested fruit fly, if it's got the same Wolbachia in it. So Wolbachia are biochemical geniuses and developmental geniuses. They have learned how to manipulate the sex ratios and mating success of their hosts, and they really haven't been domesticated.



And this is kind of interesting if you go back to the whole issue of well what happened when mitochondria first started getting into the eukaryotic lineage? Was there a period 15 hundred million years when this kind of stuff was going on? Probably was. It probably took some time to resolve conflicts and really to integrate the mitochondria into the eukaryotic lineage.



So when we think about that overall process of interacting genomes, as I mentioned the frequency of interaction is really quite important. You're not going to get tight co-adaptation of two different species unless they interact with each other very frequently.



If they're only interacting with each other occasionally, then there's a lot of stuff going on, outside of the interaction, that has costs and benefits, that is going to be tweaking the interaction traits in other directions. So it's got to be a very consistent and persistent process, to result in tight co-adaptation. So frequency is important.



And then, of course, when they interact it must make some difference to reproductive success. Then there's the issue of relative evolutionary potential: who's got the bigger population size; who has the shorter generation time; who has more genetic variation? Those things are certainly going to help determine the outcome. And then there's this issue of the Red Queen, which I will come to.



So there are some kinds of interactions, ecological interactions, that favor strong coevolution and specialization. Parasite host interactions, especially where the--this is normally a case where the whole live cycle is completed on a single host; plant/herbivore and predator/prey interactions, where you have got a fairly narrow range of species that are being eaten by the herbivore or by the predator.



And there's one here--pandas just eat bamboo, and therefore that sixth appendage, the panda's thumb, which is there for handling the bamboo shoot, has evolved. Sage grouse basically just eat sage--they're herbivores--and sage has an awful lot of upsetting biochemistry in it. If you were to go out into the American West and try to live for a week on sage, in the Great Basin, you would become very sick. Sage grouse do it just fine. They've got all kinds of--it's probably Cytochrome P450s that are the enzymes that are denaturing the plant products that would make us sick.



But the one which is really kind of sad and funny is the aardwolf. The aardwolf is a hyena that has specialized on eating ants and termites; that's the only thing it eats, as an adult. Baby aardwolves grow up with milk, from mom. And my friend, Tim Clutton-Brock, has watched the weaning process in an aardwolf, where mother is trying to convince baby to switch from milk to ants. [Laughter] And baby is not happy. Those ants do not taste good. And fortunately baby probably doesn't realize that this is the rest of life; from here on out it's ants, all the way through. Okay? So that's real specialization.



Another interaction that favors specialization is mutualism, where you have interactions that are already positive, or are becoming positive. They have symmetrical impacts on reproductive success, and these things are living in intimate contact for most or all of their life cycle. And mutualisms are very interesting and they make wonderful natural history, but they also carry the message that where it's a win-win situation, evolution is not always about competition. Evolution can be about both sides profiting from the interaction and doing better because of it, and that ends up in a mutualistic relationship.



So the relative evolutionary potential basically is determined first by generation time; second by sexual mode. Sexual partners can evolve more rapidly than asexual partners, and the partner that therefore has more genetic variation, for the interaction trait, will evolve more rapidly. So to some degree we kind of predict how the coevolutionary process will occur.



Now the Red Queen, which comes from Through the Looking Glass, by Lewis Carroll--and I'll go into that a little bit more--is the idea that there is an open-ended struggle that results in no long-term reduction in extinction probability.



Here's an example of a Red Queen process; there are many. But this would be a host/parasite interaction. And what you see here is generation time for things that have about the same generation time. Okay? So we have a host and a parasite that have roughly the same generation time.



This is the frequency of an allele. And these are interaction alleles. So these are genes that are determining how well that parasite will do on this host, and how well this host will resist that parasite. And what's going on here is that when a certain host allele goes up to high frequency, that turns out to be one that this orange parasite allele can attack very well. And so the host has gone into a state that's susceptible to parasite attack; therefore that parasite allele increases in frequency.



But, because that parasite allele is going up here, it's killing a lot of hosts up here, that host allele drops in frequency. As soon as that one drops in frequency, it makes the host less susceptible, and the parasite allele drops in frequency. And you can see there's a lag, there's a lag time between the two. Here it's sketched at about two or three generations. So this light rectangle here is indicating where the host is not having a problem, and the grey rectangle is indicating where the host is having a problem.



So Leigh Van Valen is a paleontologist at the University of Chicago who came up with the Red Queen hypothesis in 1973. And he claimed that in fact it's not just hosts and parasites; he claimed all life on earth is in fact caught up in a coevolutionary web of interactions. And his evidence for that is that the long-term extinction rate is constant. If you look over the Phanerozoic, if you look over the last 550 million years, the probability that a species will go extinct, within a given period of time, has remained roughly constant.



There's some slight evidence that maybe species have started to live a little bit longer. But, you know, broad brush, this claim is correct. Things have not gotten better at persisting, over the last 500 million years. So in some sense I think Leigh's claim is probably true. Every time a species on earth tries to get a leg up, some other species compensates. So this is where that term comes from. This is an illustration from Through the Looking Glass by Charles Dodgson (Lewis Carroll). This--Alice is a pawn on a chessboard, and Alice is supposed to, in this mental game, march down the chessboard and get turned into a queen, when she reaches the end.



And the Red Queen, who is next to her, says, "Alice, this is a game in which you run as fast as you can and you can only stay in place." So it's like one of those nightmares that you have, where you're running as fast as you possibly can, and you can't get away. That's Leigh Van Valen's metaphor for evolution: everybody is running as hard as they can and they're just staying in place; their fitness is not long-term improving.



Now I'd like to give you a few striking outcomes of coevolution. I'm going to do butterfly mimics, reef-building corals, leafcutter ants, and rinderpest. And each of these is making a slightly different kind of point, but each of them involves some absolutely stunning natural history. So let's start with mimics and models.



And these guys are, by the way, all from the Peabody Museum Collections. So, you know, if you love butterflies, you can go over and talk to the invertebrate curator at the Peabody Collections, and he can pull out tray after tray after tray of thousands of beautiful butterflies. We had one of the great butterfly biologists here, Charles Remington. And he was buddies with Vladimir Nabokov, who not only wrote Lolita, but was a lepidopterist, and so we've got some Nabokov butterflies in the collection as well. I don't know if any of these are from Nabokov. Okay?



So in Batesian mimicry you've got an edible model that evolves to resemble a warningly colored noxious species. Okay? So actually what's going on--I've actually misphrased that a little bit. The noxious one is going to be the model, and the edible one is going to be the mimic. Sorry about that. I'm going to go back and correct that. So the mimic is good to eat and the model is bad to eat.



And on Madagascar there aren't any models, and the male and the female look the same in this species. But as you go out, through Africa, you find that in different places in Africa there are different nasty tasting models, and the female turns into something that looks very much like them. So this thing has evolved into all of these other things, depending upon where they are, in Africa.



Now this is not simple. It takes a lot of genes to turn something like that into something like that. And when you go into a neighboring race--it's still in the same species; the males are still looking like that--you have to have a whole bunch of coordinated changes to make it into the other one.



So what's happened is that these genes have been pulled together, onto a chromosome, and turned into a super-gene complex, which has been inverted so that it doesn't recombine, and they're inherited as a package.



Now in Mullerian mimicry you have a process whereby things that all taste bad evolve to look like each other. Can anybody tell me why things that all taste bad might evolve to look like each other? What's the advantage in that? Yes?



Student: [Inaudible]



Professor Stephen Stearns: Right, exactly. So basically what they're doing is they're making it as easy as possible for the predator's learning process to figure out that all things that look like this taste bad. They're reducing the mistake rate, in the things that are learning not to eat them.



So these are the Heliconia butterflies of South America, and they live all on passion fruit vines. So there's a big radiation of different species of passion fruit in South America, and these butterflies all lay their eggs on those different species of passion fruit, and where they overlap, the different species have evolved to look like each other.



So what we have here is Mullerian mimicry going on here, and here; and we have Batesian going on--excuse, me, this is all Mullerian; this is Batesian mimicry. So Mullerian is everybody distasteful. This is a Batesian mimic of all of these distasteful models. This is a Batesian mimic of all of these distasteful models; and so forth.



So, those are pretty precise adaptations. I mean, if it gets to the point where a good naturalist really has to puzzle for awhile to identify whether you're looking- dealing with the model or with the mimic, and has to really know their details of morphology, it means that natural selection has precisely adjusted virtually every part of the body, so that the mimic really looks like the model.



Now a tight symbiotic relationship is between- is the one that's between dinoflagellates, that are called zooxanthellae, and their corals. And there are also--so here is a coral. And, by the way, there are also zooxanthellae living in the lip of this giant clam.



So this giant clam and the coral are both farming algae. And the algae are photosynthesizing and delivering photosynthate, to the host. And you can see here the chloroplast of one of these algae, and its body is in here, and it is producing photosynthate; and these are the starches that it's accumulating.



Now the relationship goes something like this. The dynoflagellates, which by the way look like this when they're out in open water; they're really quite lovely. And remember, these are some of the guys that have so many membranes around their chloroplasts, because they're the result of three or four ingestion events over evolutionary time.



If they produce say 250 joules of energy, through photosynthesis, they export 225 of it to the corals; and they only put about .2 into growth and 25 into respiration. So they've been almost completely domesticated. Pig farmers have been trying for hundreds of years to get pigs that would be this efficient, for humans, and these corals have turned these dinoflagellates into a energy conversion machine that's just incredibly efficient, from their own point of view.



The corals, of course, have tentacles, and they will feed on zooplankton and stuff which is out there, but they only get about 1/10th of their energy from feeding directly; they get most of it from photosynthesis. And then what they do is they put a little bit of it into growth. They put a lot of it into their calcified skeleton--so basically you're looking at where reefs come from; this is how a reef is produced--and then they lose quite a bit to respiration and to the mucus that they produce in their feeding. So they're getting about ten times the energy from their symbiotic algae as they are from direct feeding.



Now one of the implications of this is this is why you do not find reef-building corals deeper than 20 meters. It's because there's not enough light for the algae, any deeper than 20 meters. Okay?



Now the crazy thing about this system is that a baby coral has to acquire the algae in each generation, and the algae exist as independent species. So the algae are actually incredibly phenotypically plastic; they have a free-living form, and they have a domesticated form, and they can reproduce both ways.



And that's very interesting because from the point of view of the algae, the free-living form is the source and the domesticated form is a sink; and it's therefore puzzling to see how it was that the corals were able to engineer the algae. There's got to be some kind of coupling of the cycle so that what goes on in the coral feeds back into the free-living form; otherwise you couldn't get this tight adaptation. They're re-domesticated in each generation, in the coral.



Okay, now for a macroevolutionary, coevolutionary story. How many of you have been in the Tropics and have seen leafcutting ants? Four or five, six. These guys are great, and they form huge colonies. The chamber that they can form is the size of this dais up here. It will be three or four feet high, and if you're out in a rainforest, the cutting activities of the workers will actually clear all the leaves off the trees, over the chamber, right to the canopy; so you kind of exist in a well in the forest, where the ants have essentially punched right through, 200, 250 feet up, taking out all the leaves.



And they take them down, into their underground chamber, where they chew them up and they feed them to a fungus. And they domesticated this fungus 50 million years ago. Okay? Humans figured out how to domesticate wheat 10,000 years ago. The ants domesticated the fungus 50 million years ago. They're the first farmers; well the corals probably did it earlier. Okay? But this is another domestication event.



So they cultivate this fungus clonally. The fungus can't reproduce sexually, in the colony, and it looks like it's been asexual ever since it was domesticated. It's a monoculture. Now in human agriculture, a monoculture is incredibly vulnerable to plant diseases. Having a continent covered by a single strain of wheat, or a single strain of sorghum, or a single strain of sugarcane is a bad idea, because pathogens will evolve onto that particular monoculture genotype, and they can go through in an epidemic and wipe the whole thing out. So having a mix of genotypes in agriculture is a very good idea.



Well that's not what the leafcutter ants did. They have a pathogen that can attack their own--okay?--and it's also a fungus. So there's another fungus that can come into the colony and take over their own fungus. But to fight it, they cultivate a bacterium, and they use that bacterium as a defense against the enemy fungus. And they have a- they've evolved a special morphological pouch in which they carry this bacterium.



And you'll notice that because it's a bacterium, it has a short generation time. So they have the coevolutionary arms race matched up in terms of timing. They have a bacterium that can evolve as fast, or faster, than the fungus that infects them. So they have not only domesticated their food supply, they've also invented a health delivery system to keep it healthy; they have a pharmacy.



Now if you look at the macroevolution of this system, what you see here basically is the phylogeny of the ant, the phylogeny of their fungus, and the phylogeny of their parasite, over here. And the thing that I want you to notice is that although it's not absolutely precise, these things match up pretty well. So the parts that are in blue--I mean, sometimes you find a few more parasites, hitting a few more cultivars, but roughly speaking if there's a branch at a certain point in the tree, it is a branch for all three things. It's not precisely matched, but it's pretty close. This is an amazing system.



And when Ulrich Mueller, who has worked on it--and this is actually-- he's a co-author on this paper. He's a professor at the University of Texas in Austin. When he visited and gave a talk on it, I asked Ulrich, "How did you come to this system?" And he said, "Well, about twenty-five years ago I took an OTS course, and we were sitting there in Costa Rica, and we played the 50 Questions game, and my question was about leafcutter ants." And that's his career. Okay? Questions have profound influence.



Okay, rinderpest, the final one in this series. The point about rinderpest is this. I'm giving you this example to show you what happens when evolution has not occurred; and that gives you a feel for what has happened when evolution has occurred. Okay? So this is the rinderpest pathogen. It's a virus, and it attacks cattle, buffalo, eland, kudu, giraffe, bushbuck, warthogs and bush pigs; those are all ungulates. So it is attacking one clade on the mammalian tree; they're all things that have two hooves.



And it evolved in Asia, and it came into Europe through human invasions, repeatedly. So things in Asia and Europe had evolutionary experience of rinderpest; they'd been exposed to this disease. However, things in Africa had not, and it got into Africa probably either when the Italians went into Somaliland, or when General Gordon brought in some Russian cattle when he went to relieve Khartoum; so in the 1880s rinderpest got into Africa, and it came in because Europeans were bringing cattle in with them. And by 1890, it had crossed the Sahara, and gotten into Southern Africa.



So there were some direct consequences. It eliminated--in the 1890s it took out most of the domestic cattle and wild buffalo, and many related bovids. This caused enormous famine and disruption in the humans who were living in Africa and who either had domestic cattle or nomadic cattle. So, you know, the Masai really got hammered by this.



Only one species went extinct--it was a species of antelope--but the distributions of all of the other wild ungulates in Africa were altered, and they remain altered to this day. They're springing back in some areas, and there are now vaccines for rinderpest that are being used on domestic cattle in places like South Africa. So the distributions are altering, but you can still see the signature of the event.



People lost food supplies, and there was an outbreak of endemic smallpox, while this was going on. So it started causing a cascade of effects, through the ecosystem. There were epizootics--an epizootic is like an epidemic, except it happens in populations of wild animals.



So there were epizootics in 1917/18; so right at the time of the outbreak of the World Flu Epidemic, people in Africa were also getting hammered by another outbreak of rinderpest hitting their animals. 1923; 1938 to '41. This is the kind of habitat in which rinderpest was spreading.



There were some interesting indirect consequences. So over a lot of the infected area, tsetse flies disappeared, and the reason tsetse flies disappeared is that they make their living off of wild ungulates. So if there aren't any wildebeest or giraffes around for the tsetse flies to eat, they will disappear from the area. Now they require trees and bushes as their habitat, and herbivores for their food.



Now when the herbivores disappeared because of rinderpest, the tsetses lost their food, but their habitat sprang up, because there weren't ungulates eating the bushes that the tsetse flies would live in. When things like wildebeest disappeared, the lions got hungry, and there were outbreaks of man-eating lions. So in the 1920s, during a rinderpest epidemic, there was one lion that killed 84 people.



When I first went to Queen Elizabeth National Park, in 1992, there were people living in the park, squatters living in the park, and they would try to get to the store at Park Headquarters, on a bicycle, and the lions had learned that it was possible to separate that blob on top of this funny two-wheeled thing, from what was moving so fast. And so like pussycats chasing balls of twine, they had gotten into knocking over bicycles and eating people, and there had been thirteen people who had been killed in the two months before we arrived, in Queen Elizabeth National Park. That kind of thing still goes on.



So the lions contributed to the abandonment of big areas, and thickets of brush grew up. So the ungulates went down, and the people pulled back, and the bushes grew. Now when the ungulates developed some immunity to rinderpest, and they moved back into the abandoned farming areas, they then became hosts for tsetse flies that could now live in the new bushes. Okay? So you see rinderpest goes in, and it changes a bunch of stuff ecologically, and it changes the geography of Africa.



And the flies transmit sleeping sickness; so they do that, by the way, both in the ungulates and--sleeping sickness is a real problem in domestic cattle, as well as in people. And so the humans really pulled out of this area, and they remained absent even after the lions switched back to eating the ungulates.



If you go into the Serengeti, just west of Seronera, there is a valley between Seronera and Lake Victoria, which is called The Valley of Death, and that's because of the sleeping sickness that's endemic in the valley; and that's an example of what happens in this process. And by the way, we call these areas now, to a certain extent, the National Parks of Africa. So if you wonder why those parks are where they are, in part it's due to the history that I just told you.



So rinderpest changed the ecological structure of at least half a continent, for about a century. The consequences were pretty bad, and they were only kind of predictable in retrospect. Nobody had the knowledge, when General Gordon relieved Khartoum, with a few Russian cattle in his supply train, that they were carrying a virus that would do this to a whole continent. Okay? I think that this is one of those places where we have to be extremely modest about how much we understand about ecology and evolution. Bad shit can happen.



So the same thing happened in the New World when Europeans, who were relatively resistant to smallpox and measles and things like that, brought with them their diseases, and that is why they were able to overthrow the Aztec civilization. If you ever ask yourself, how the heck did a couple of hundred Conquistadores wipe out an Aztec army of 100,000, the answer is the Aztecs were all sick and dying, and by the time the Conquistadores got to Mexico City, from Vera Cruz, the epidemic had spread ahead of them; and that happened all over the New World and all over Polynesia.



So the point of this basically is we want to compare what happened in Africa with what did not happen in Asia and Europe. The Eurasian ungulates have a long evolutionary history with rinderpest, and the ones that we see there are the ones that are not extinct; they made it. Okay? And if we summarize coevolution as a whole, there are lots of things that coevolve. It's not just species that are coevolving with each other; it happens at many scales. And that means that other living things are among the most important elements of the selected environment.



So you shouldn't think of organisms as being faced only by challenges of temperature and rainfall and stuff like that. Really, once life got going, the different species on the planet became each other's most important interaction partners. Part of this is running just as fast as you can to stay in one place; and this Red Queen concept is probably particularly appropriate for the virulence resistance paradigm, and for the evolution of sex as an adaptation against parasites.



And as the rinderpest example shows us, the extent of coevolution is particularly strikingly revealed when you see a foreign species invade another continent after a long period of isolation. Okay.



[end of transcript]

Evolution plays an important though underutilized role in medicine. Evolution guides how our bodies respond to various treatments, how pathogens will respond to treatments, and how pathogens' responses will change over time. Pathogens oftentimes will evolve to an intermediate level of virulence where they become strong enough to infect a host and reproduce, but not so strong as to kill the host before it can spread the pathogen.



Reading assignment:

Stearns, Stephen C. and Rolf Hoekstra. Evolution: An Introduction, chapter 19

Transcript



March 2, 2009



Professor Stephen Stearns: Well today we're going to talk about evolutionary medicine. And there are some resources that you can use, if you get interested in this. There's a book, got twenty-three chapters in it. There is a website called Evo-Med Symposia, that you can go to, and you can have talks on the evolution of HIV, antibiotic resistance, etcetera; and that's in Streaming Digital video. So each one of those talks lasts about an hour. So if you get interested in any of that, you can actually see--and by the way, it's not just the PowerPoints, you see the people giving the talks. So if you want to actually more or less meet these people and see what they're like, that's a place that you can do it.



Now the range of issues in evolutionary medicine is really quite large. And I often get asked--you know, people haven't heard the term before, they don't know what evolutionary medicine is. So here is a description. Okay? Part of it is that we contain traces of our evolutionary history and they bias our responses in significant medical issues. So there's the hygiene hypothesis about autoimmune disease. There is our genetic variation for resistance and drug response. There are traces of the selection that illnesses, that diseases, have written on our genome.



Then there are issues in reproductive medicine. And the human life history is really quite special. If you contrast us to chimpanzees or bonobos, human females are capable of pumping out children about twice as fast as a female chimpanzee, and the only way they can do it is by having help. So it indicates that we have been highly social for a long time, and our life history has responded to that.



You know something about genetic conflicts, imprinting and mental disease, because I talked about that earlier. Then there are the issues of ovacytic atresia and selective abortions and mate choice, which are an interesting part of reproductive medicine.



A big part of evolutionary medicine has to do with the evolution and ecology of disease. And diseases have adaptive strategies. They have their own agendas. They have, many of them, have developed ways of avoiding our immune responses, of manipulating hosts. Some of them manipulate us; that's what coughing and sneezing is about. That's also what making us extremely tired and lying down is about, in malaria. Their virulence evolves, they evolve drug resistance rapidly, and those are very significant medical issues.



Then there's all the information that's coming in now from evolutionary genetics and genomics about where viruses originated. So, for example, the detective work necessary to determine that the sooty mangabey was the ancestor of HIV-2 is done with molecular phylogenetics, and that the chimpanzee is the ancestor of HIV-1; that the SIV living in the chimpanzee is the ancestor of HIV-1 is done that way.



Then there are very significant differences between different kinds of bacteria, in terms of their genetics and their population biology, particularly in how readily they can do horizontal gene transfer. So that if a bacterium in one species evolves resistance to a certain drug, how likely is it that that resistance gene will get into another species? Okay? That's obviously a critical question, and it depends on the particular kind of evolutionary genetics that that bacterium has; and they vary in this respect. Okay?



And then there are all of the issues about under what conditions do new diseases emerge? And that itself is quite a growing field. Then there's all about the degenerative diseases. Okay? How did aging evolve? And given that we have an evolutionary theory of aging, what can we expect to be the characteristics of the aging organism? Are they going to be simple or complex; and if we fix one thing, will another thing break? That kind of issue.



We can view cancer as an evolutionary process. Every cancer is its own little microevolutionary process. A population of cancer cells is a genetically heterogeneous ball of growing cells; that has important implications. And then there are links here in degenerative disease--in heart disease, obesity and diabetes--back to traces of our evolutionary history. So that's the scale of the issues.



If we think about the--oh let me just run through that quickly--if we think about traces of our history, we usually think about hunter-gatherers and the kinds of groups that they lived in. If we think about the evolutionary biology of diseases, we think about things like Ebola and HIV and malaria. And if we think about degenerative diseases, we think about this process. So that's what evolutionary medicine is about; it's about a lot of different stuff. Okay?



So I can't talk about all of that. I've just described the course that I gave last fall in Copenhagen. Okay? It took two months. [Laughs] So I could give you some important classical themes. I could give you some surprising new insights. I could give you some overarching general messages, such as our bodies are compromises that impose indirect costs; or that evolution takes time; or pathogens have their own agendas.



I could present research, stuff I've worked on myself. I've done a fair amount on the evolution of aging, and I'm currently working on how natural selection is operating in contemporary human populations. Or I could give you messages primarily aimed right at practicing doctors; so practical applications in clinic and public health. And this is what I chose: I chose Mismatches to Modernity.



So I'm going to talk a little about thrifty phenotypes, and parasites and autoimmune disease; and then I'm going to talk about how pathogens have their own agendas and evolve rapidly. Okay? So I hope you've got the picture. This is a small portion of the subject matter of evolutionary medicine. But these are arguably important themes.



So the point about thrifty phenotypes is this: Early life events are failing to predict late life environments. Perhaps they used to be good predictors, or perhaps those early life events were correlated well with the environment in the Pleistocene, for ten or fifteen years, something like that.



What we do know is this: if you nutritionally stress a mother and infant, the fetuses and infants will have increased risk of obesity, diabetes and cardiovascular disease fifty or sixty years later. And the initial data that demonstrated this came from the Dutch Hungry Winter.



The idea is that stress early in life is switching the individual into a physiology that's very effective at conserving energy, but it is inappropriate if there's an adequate diet. So the muscle cells become insulin resistant, fat becomes concentrated in special depots. And we now have a lot of data indicating that this is the case in humans. So they come from the Dutch Hungry Winter of '44/'45, when the Nazis basically cut off the food supply to Amsterdam, and actually to much of Holland.



But you can also see this when there have been historical famines in Scandinavia. In the late nineteenth century there was a famine in Finland; and more recently, in the U.K. and the Philippines. And you can reproduce this in rats and sheep. By the way, the fact that you can reproduce it in a model system is quite important, because it means that for whatever reason that thing evolved, that kind of reason must also have been there for something as short-lived as a rat.



Now if we look around the world, about 20% of American adults are obese. Interestingly, in rural Mexico, 60 to 70% are obese. That's not something you'd necessarily expect; go into rural Mexico, you don't necessarily think that those people have a lot of money to eat a lot of food, but they are obese.



The incidence of diabetes is exploding; so late-onset diabetes is exploding. As you might expect, most of them are in India and China, simply because the populations of India and China are so large. And this is becoming a really significant portion of the world health budget. So these are significant issues.



And if you look at percent obese across many countries, the least obese nation is Japan, and a lot of the European countries kind of have low levels. But the ones that have very high levels of obesity are the U.S., U.K., and Germany, Australia. These are not necessarily the ones in which this kind of nutritional stress early in life would be very frequent.



It is much more likely that as countries like India and China, and countries in Africa and Mexico, go through the demographic transition, and go through the economic transition into developing countries, so that they have a parental generation that was more food stressed, and an offspring generation which is more well fed, and more exposed to junk food, that you will get this kind of a response.



So when we look at this kind of data, there's a lot of this that probably really isn't due to the thrifty phenotype hypothesis. I would guess that of the total amount of obesity that you see in the world, the part which is really due to a developmental switch being thrown early in life, and then setting that phenotype up to respond inappropriately to a rich diet late in life, thereby developing heart disease and obesity and so forth, at about the age of fifty or sixty, is probably somewhere down around 5%. So not all of it, but probably a significant component.



And the argument is that that was something that was adaptive in the Pleistocene environment, because if you could switch the offspring into a thrifty phenotype, it would have a higher probability of surviving the dangerous childhood years and making it perhaps to its first reproductive event. And, in that environment, what was going on at age fifty or sixty was probably irrelevant because most of the population was dead by then anyway. So that's the kind of evolutionary argument that gets at it.



I don't think we actually know what's selected for this. I think that we have a plausible evolutionary story to tell about it, but the fact on the ground is that it really happens. So it's important to know about, and it might be for the evolutionary reasons that I just mentioned, but we don't know.



Okay, now here's one where we are a little bit more certain. And again, this is a hypothesis that is in the category of things where humans are mismatched to modernity. So they are experiencing a disease which is caused, in part, by our historical shift into a civilized state. It runs like this: our immune system coevolved with worms and bacteria.



So it more or less evolved on the assumption that we would always have worms and bacteria in our bodies. And when modern hygiene--so basically good clean water systems--and antibiotics take out the worms and bacteria, our immune systems respond inappropriately. We can see that autoimmune diseases are actually exploding. So asthma, allergy, Type-1 diabetes, multiple sclerosis, other auto--Crohn's disease--other autoimmune diseases are increasing very rapidly. And as the infectious diseases have gone down, the autoimmune diseases have gone up.



So there are some spatial correlations that are suggestive. I'll show you some data that are tighter than this. But if you look across the planet, you can see that where diabetes, Type-1 diabetes is common. Type-1 is an autoimmune disease, okay? You see Type-1 diabetes being common basically in Europe and in Australia, and it's also fairly common in Saudi Arabia. And if you look at where worms and leprosy are common, where countries that have a fairly high incidence of these different worm infections, those are pretty much across the Tropics. The countries where there's no data basically, are in white. So this is a partial plot. And if you look at Type-1 diabetes against tuberculosis, you see where there's a lot of Type-1 diabetes there's not very much tuberculosis, and where there's a lot of tuberculosis there's not very much Type-1 diabetes. Okay? So that's a negative spatial correlation.



There's more data than that. In Germany, and in other European countries, farm children have fewer allergies than city children. If you go to Gabon and you go around testing by just nicking people on their arms--which is a very easy test; you just apply a little bit of dust mite egg to somebody's arm and see whether they have a reaction--the kids with schistosomiasis don't have so many allergies, and they don't have a reaction to dust mites.



And if you look in these countries, adults with less asthma are more likely to be infected with nematodes. And just let me comment before I take that one off, that if you are a doctor working in the Tropics, you almost never see autoimmune disease. So if you go into Médecins Sans Frontières, and you go to Gabon, or you go to the Congo, you'll see a lot of infectious disease, and you will see a lot of worms, but you will not see very much autoimmune disease. That's the take-home message from this summary.



Now how might this work? Well worms are big, multicellular parasites, and they have to live in our bodies a long time to reproduce successfully. When they send their eggs out, to get into another host, those eggs are going into an extremely risky environment, and it's not very likely that any single individual egg is going to make it. So the worms have evolved ways of living in our bodies, for a long time, without being knocked out by our immune systems.



This has been going on for hundreds of millions of years. They're very good at it. They are interfering with signaling pathways that also happen to be the pathways that elicit allergies and asthma. Now think about it from our point of view. We got these worms in our system, and they got to be really good at living in our bodies for a long time, but we have an immune system that wants to react to them with a big inflammatory response, but it's not going to be able to get rid of them, because the worms have out-foxed us. So we have to make the best of a bad deal.



What we have to do is we have to down-regulate our inflammatory response, in the presence of worms, so that we don't damage ourselves; because inflammatory responses turn out to be one of the most damaging parts of degenerative disease.



That's what's going on in arteriosclerosis. That's what's going on in rheumatoid arthritis; you know, there's just a lot of inflammatory response, damage can happen to your body. So our immune system basically down-regulated, in the presence of worms. Now that means both sides of this co-evolutionary interaction have evolved. So the causes really are rather complex.



The parasites have been removed, that actively down-regulate the immune response. That leaves inappropriate responses of our anti-worm machinery, and that anti-worm machinery lacks proper targets and is fooled by inappropriate targets. There is ongoing research right now to see whether or not this is in part the basis for nut allergies, which--things like peanut allergies--which have really exploded. It appears to be possibly part of it, but probably not the whole story. And then, of course, we have changed our inflammatory response.



And another interesting part of this--and again this is open research--imagine your body having come to evolutional equilibrium with worm infections. So the worms are down-regulating your immune system, and your immune system is just--it has a lot of other things to deal with besides worms, so it's cranking along, it's producing a range of cells that can react to different kinds of invaders. And it has a screening apparatus, which is in your spleen and in your thymus glands, to screen out any molecule or any population of cells that is recruited by your immune system to attack your own tissue. And it's screening along at that level.



Then you pull the worms out. The immune system is no longer down-regulating because of the presence of worms; the immune system cranks up, and it throws a lot of stuff at that screening apparatus. But the screening apparatus didn't evolve to deal with that much stuff. So it's kind of leaky. So it is letting through more cells that might react with your own tissue. Okay?



That's a hypothesis; that's not a demonstrated fact. But what I'm trying to do is I'm trying to indicate to you that this issue of autoimmune diseases arises logically, either at the points where the worms had been manipulating signaling in the immune system, and then that has been withdrawn, or it is operating on the screening mechanisms that are built in for the immune system; both could be going on.



Now, what kind of data have we got? Well here--this is kind of small, but basically what you've got here is a knockout mouse that simulates Type-1 diabetes. Okay? So it's a model mouse; people have genetically constructed a model mouse, to make it like Type-1 diabetes in humans. And then they have infected it with various kinds of worms to see whether or not it is changing the T-cell bias in a way that would be plausible to basically down-regulate autoimmune disease. And these are things that prevent Type-1 diabetes in knockout mice.



So Schistosoma will do it, Heligmosomoides will do it, Trichinella will do it. Mycobacterium--that's TB and TB's relatives--will do. Salmonella will do it. Basically infectious agents are antagonists of Type-1 diabetes in model mice.



And if you ask a little bit more widely, if you have an animal model for another kind of a disease, what can we treat it with? Well we've got Schistosoma, we've got Trichinella, Trichuris and so forth. These things will prevent colitis, inflammatory bowel disease, collagen-inducted arthritis, Graves' thyroiditis, and so forth, in model systems. So there's some evidence in animal model systems that this works.



So if you decided that you wanted to do therapy on humans, using these nasty worms, which have a big yuck factor, which one would you choose? Well you would want to have a worm that doesn't really cause much pathogenic problem itself in a human.



You wouldn't want it to multiply in the human. You'd want to be able to regulate the dose. You wouldn't want the infection to get away from you, in treating a human. You wouldn't want it to be spread. You wouldn't want it to alter the behavior in patients that have depressed immunity. You wouldn't want to be affected by common medications like aspirin and stuff like that. Okay?



Well, which one will do that? It turns out this pig whipworm has these characteristics. And what you can do is you can breed these things in the lab--I've seen them in Rick Maizels' lab in Edinburgh, growing in a little vial; they're whipping around in the little vial; they look like little pieces of thread--and basically you use their eggs.



Now here's some data. Patients with Crohn's disease and ulcerative colitis improved after ingesting 2500 pig whipworm eggs. I mean, you guys all have issues with what they're serving you in the dining hall. [Laughter] How about a little pig whipworm egg?



People with Crohn's disease who got a fairly prolonged treatment with this stuff responded well. Patients with ulcerative colitis, in a double-blind, placebo controlled trial--which is another step up in rigor--did better on worm eggs than they did on placebos. But this is the one that really gets me, and it's about multiple sclerosis. Okay?



This is a very, very nasty disease, and multiple sclerosis is an autoimmune disease that attacks the sheaths on the axons in your brains, and it does so in a slightly different way in each individual. So the symptoms start developing in different ways, but basically what's happening is that you're losing your brain.



And these are some of the symptoms: numbness, tingling, pins and needles, weakness, spasm, spasticity, cramps, pain, blindness, blurred vision, incontinence, urinary urgency, constipation, slurred speech, loss of sex function, loss of balance, nausea, disabling fatigue, depression, short-term memory problems. People with multiple sclerosis often go to Switzerland to commit suicide; I think about 60 of them have, because they're faced with something which is a very painful way for life to end.



Well there was a case control study done recently in Argentina that showed that the progress of multiple sclerosis is a lot slower in the patients that are infected with parasitic worms. And that was convincing enough--this was a case control study; so for clinical medicine that's sort of the gold standard.



You take a bunch of people and you match them with cases and controls, and then you see what happens differently in the two populations. So the data there was convincing enough to persuade the NIH to begin a clinical trial in Iowa in which MS patients are being treated with the eggs of pig whipworms.



Now this is the data from Argentina, and the X--by the way, the four panels are four different ways of measuring the progress of multiple sclerosis, and all four panels have a five-year time axis on the X-axis, and then they have some measure of multiple sclerosis on the Y-axis.



And in all four panels the uninfected patients--they were matched at the start, infected and uninfected by worms, and at the same stage of multiple sclerosis--the uninfected patients got worse, and the infected patients did not get worse. Very clear.



When I first got in contact with evolutionary medicine, this hypothesis wasn't really out there yet, or wasn't very prominent. It came to my attention ten years ago. I didn't believe it at the time, and I'm actually rather astonished that this is the part of evolutionary medicine that is actually resulting in an important clinical result that could change treatment and save a lot of agony. I hadn't expected that.



So humans evolve more slowly than their cultures, and therefore we are mismatched to modern life. This is important in both our diet and in our cleanliness and our hygiene. And it appears, certainly for the hygiene, and quite possibly for certainly people who are born very food stressed and then encounter junk food, that that causes serious medical problems.



So one of the visions of evolutionary medicine is that we evolved to a diet and an ecology and a social life and a degree of cleanliness that was characteristic of a Pleistocene hunter-gatherer group, and that that's now changed radically and we haven't caught up yet; our bodies have not yet adjusted.



The other thing that I want to tell you about basically is about how pathogens evolve. And they evolve very rapidly in response to things that we do to them, both to antibiotics and to vaccines. So the antibiotic resistance story is in large part a story about hospitals, because that's where most intense use of antibiotics is. Virulence also evolves, and there are lots of interesting stories about how virulence evolved.



For example, plague in Europe, from 1348 to 1350, getting less virulent as it goes northward; or a new strain of syphilis coming into Europe from the New World and getting into Naples in about 1500 and preventing the French army from taking over Italy at that time, and then decreasing rapidly in virulence as it spread. There are lots of stories like that in history, and they're interesting.



But the issue that confronts us today actually I think is most tightly focused on what vaccines will do, because we are now contemplating vaccines for a new kind of disease, not a childhood disease. We're not looking at vaccines that basically sterilize a population. We're looking at imperfect vaccines, and the issue is will they cause virulence to increase? So let's look at these.



So a little bit about antibiotics first. Okay? Almost all of the bacterial genes that allow them to process the drugs that we use, and deal with those drugs, that provide them with resistance, evolved before the human drug industry existed. And that's because bacteria have been engaged in warfare, chemical warfare, with each other and with fungi, for hundreds of millions of years.



And they are biochemical maestros. They have developed a large spectrum of synthetic capacity, and it's out there naturally in nature. There's about a ton of bacteria per acre in a cropland; that's about 1017th bacteria. That's an enormous number. There's a lot of info that can be stored in 1017th bacteria.



Here's a little bit of data. Drug resistance evolves in the soil and in wild animals. So if you go out and just take out samples of spore-forming bacteria from soil, that's not near a hospital, that's out there, every single one of 480 strains of bacteria was multiply resistant, and there was no existing class of drug that was effective against all strains. That's just natural variation that's out there. Okay? That is the downside of biodiversity.



There's a lot of evolutionary potential in natural bacteria. If you go around the outback, in Australia, and you sample enteric bacteria, that is gut bacteria, from various Australian mammals--you do this essentially by collecting feces--what you find is that they have multiply resistant strains of bacteria; and they have never been close to a city, or to human beings that are taking antibiotics.



So that's on the one hand; that's what's out there naturally. Now what are we doing to it? Well the agricultural use of antibiotics is quite important. I'm going to talk a bit about hospitals in a minute. But the reason that farmers use antibiotics is that by reducing the amount of energy that their pigs, cattle and chickens have to put into resisting disease, their pigs, cattle and chickens grow more rapidly. So it pays them. If they use antibiotics, they increase their production.



So one antibiotic that's actually quite critical is vancomycin. Vancomycin has been the last line of defense against multiply resistant staphylococcus aureus for about twenty years. You don't want resistance to evolve to vancomycin. If it does evolve to vancomycin, it becomes very hard to do surgery in hospitals.



Well Danish farmers were using vancomycin, and the Danish government noticed that and banned it. So we have a before/after comparison of how frequently do you pick up vancomycin resistant enterococci bacteria in Copenhagen, in the city? Well it dropped from 12% to 3%. There was a 9% rate drop in the rate at which doctors picked up vancomycin resistant bacteria in the city, when they stopped using it out there on the farms.



That is a measure of how dirty the meat processing plants are, on the one hand. Okay? There's crap getting into the meat. There's a movie about that, by the way, about McDonald's; it will really turn your stomach. But it also indicates just how important the widespread agricultural use is.



Now the other place where there's really a lot of antibiotic use is in the hospital. Okay? So the Center for Disease Control estimated--I think this is in 2003--that there were 90,000 residents of the United States that went into the hospital for some other reason, picked up a resistant bacterium, and died of a bacterial infection that they didn't have when they went into the hospital.



And when the cynical researchers checked the claims to the health insurance companies, they discovered that the actual number was probably ten times higher than that. So this is just for comparison. AIDS was killing 17,000 a year in the U.S. at the time; flu about 37,000; breast cancer about 40,000. So there are actually more people who were dying of bacterial infections that they acquired in hospitals than of all of these leading killers combined.



Now the bacteria that live in hospitals are almost all either resistant or multiply resistant, because that's where so many antibiotics are used. And it's a good thing to use antibiotics in hospitals. Okay? When you bring somebody into the Emergency Room, or if they're in Intensive Care, and they are possibly just a few hours away from having to have an operation, you don't want them to be in a susceptible state. You want them to be clean, when they go into that operating theater. So you're going to use antibiotics on them to increase their probability of survival, if they have to have a major operation.



But the consequence of that, which is of benefit for the individual, is a cost for the population. And resistant strains are much more expensive to cure. The cost of curing one case of TB, if it's not resistant, is about 15 to $20,000.00, and the cost of curing one case of multiply resistant tuberculosis is about a quarter of a million dollars. So it's about ten times higher. So the economic burden for the U.S. was about 80 billion annually, for resistance, and the economic burden for the planet is probably about a trillion. It's a big problem.



So basically I'm going to just put--I'm not going to read all the way through this. Okay? Basically what this says is people move back and forth between hospitals and nursing homes, and when they move, they move the bacteria with them. And so however you're managing it in the hospital, you have to deal with a situation where it could be coming back in.



And I can tell you that if you operate a nursing home, you're just deathly afraid that one of your patients in the nursing home is going to come up with a multiply resistant strain of bacterium, because in old people that can go through and just wipe them out. You'll get incurable pneumonia very quickly occurring.



This idea--well let me just go back here. In this context of the ecology of hospitals and nursing homes, there's been some fairly sophisticated thought given to how should we manage the use of antibiotics. The kind of simple-minded way, which has often been used, is that well we'll just cycle the antibiotics.



We'll use Antibiotic A for three weeks in the hospital, and then we'll replace it with Antibiotic B; and that way every time they start to evolve resistance to Antibiotic A, they get hit with Antibiotic B, and so forth. It turns out that produces a selection regime which is extremely effective at causing the rapid evolution of multiple resistance; happens again and again and again.



Turns out the best way to really screw up the bacteria is to assign antibiotics at random, to individual patients within the hospital, and change them about every two days. Well that would drive the nursing staff crazy; I mean, that's just hard to manage. Right? But that's the most effective method.



Well if we apply that to chemotherapy, what we notice when we look at the community of oncologists is that many of them aren't aware that a cancer is a genetically heterogeneous population of cells. I mean, the whole thing that gets a cancer going is an optimum mutation rate, and those cells continue to mutate; so they become quite genetically heterogeneous. It takes seven to nine mutations to turn a stably differentiated cell into a cancer cell, one after the other.



And those cells then--and by the way, the mutations that do it are often mutations to the DNA repair apparatus. So cancer cells tend to have a pretty elevated mutation rate, and they become- a cancer becomes very genetically heterogeneous. So if you start prescribing one chemotherapy, and wait until it fails, and then start another one, you are applying a selection pressure that very effectively selects for resistance to chemotherapy.



So if a more sophisticated strategy were used, it's been calculated that the lifespan of cancer patients might be prolonged by well several times; it all depends on the cancer. But say take something like breast cancer, instead of perhaps having a ten or twenty year potential survival, you might be able to manipulate the chemotherapy to have a thirty to forty year potential survival; which for many women would get it to their normal lifespan. So this is a place where evolutionary models can actually really help to better manage the use of antibiotics.



Okay, virulence. Now I've used Ebola, HIV and malaria to symbolize the three different stages in the evolution of virulence when a disease emerges and moves into the human population, and then starts to become adapted to it.



So the first phase, which would be Ebola, Lyme disease, bird flu, SARS, rabies, it's accidental; it's an accidental infection. It's coming in from another species, it's not adapted to us yet, and sometimes these things are just incredibly virulent. By the way, they aren't always. We probably don't even notice the thousands that come into us and never take root and die off quickly, because they simply pass without having caused any major disease.



But the point, the reason that some of them, some perhaps small proportion, are highly virulent is that they've never had any evolutionary experience in humans, and they're not adapted to the level of virulence that's best for them. They kill us too quick; they kill us so quickly they can't get out. Ebola is essentially a self-snuffing disease. It won't spread out of one village, because everybody's dead too quickly for it to transmit.



Phase Two would be one in which the parasite's been established, but it's still far away from its optimal virulence. Okay? So this is probably the case with HIV. The virulence of HIV is probably still evolving. It's been in humans, we think, about seventy, eighty years, something like that. And the Myxoma virus that was used on rabbits in Australia. So it evolved its virulence downward in Australia, because it was killing rabbits too fast.



Then in Phase Three you're dealing with a parasite that's well established, it's been in that host for a very long time. It's probably at its optimal level of virulence. Okay? So yes, it will kill some people, but it doesn't kill them too fast. It kills them at a rate where most of it can still get out and get into another individual, before the first host dies. And that's probably the case with malaria and tuberculosis.



So let's take something which is in Phase Two, and put it to work. So here's where virulence evolution actually becomes part of a medical technology. Microbiologists have been using serial passage to produce attenuated vaccines for a long time. And what an attenuated vaccine is, is a pathogen that would cause a serious disease, but it's been evolutionarily changed, so that it's attenuated. It will infect you but it won't make you sick, and it will therefore elicit a very strong immune response, which is also effective against the unattenuated relatives.



And that's been used to produce the Sabin oral polio vaccine; the measles, mumps, rubella, yellow fever and chickenpox vaccines; one flu vaccine; and a TB vaccine and a typhoid vaccine. So this is actually showing you that rapid evolution of virulence is a medical technology, and has been now for fifty years. The reason it works is that pathogens evolve rapidly.



And the results demonstrate that there really are widespread tradeoffs in performance on different hosts. This tradeoff right here, that you do well on one host and poorly on another--that a jack-off-all trades is a master of none; the master of one doesn't do well on another--limits host range and constrains the emergence of new diseases. So these kinds of data, which basically were directly technically related to the production of vaccines, are indirectly telling us a lot about pathogen evolution and ecology.



Here's the way it works. What you do is you get a nice genetically homogenous mouse, which is not going to be any kind of a genetic challenge to the parasite. So you give it a sitting duck--except it's a sitting mouse--and you inject it with parasite; parasite grows exponentially, and while it's still in exponential growth phase, you take some of it out.



You remove its transmission costs. You take away any tradeoff it might have had with transmission. Okay? So it's going to become really bad at transmission, but boy does it get good at growing in this thing. You extract it, you re-inject it, and you let it go through exponential phase--you just keep it in exponential phase the whole time. You're killing mice like crazy. This is what happens. This is a passage through mice. This is the percentage of dead mice. This is salmonella. So you start it in a new host, and it gets more and more virulent in that host. As it specializes on its new host, it gets really good at growing in that host.



This is what happens through passages in cell culture. And this is the number of monkeys being killed for polio virus. And this is actually Sabin's original data. Okay? So he's passaging polio through cell culture. So it's really good at living in cell culture. It's getting really lousy at living in monkeys, and the longer it lives in cell culture, the fewer monkeys it kills, until after 50 passages in cell culture it isn't deadly at all, in monkeys; and at that point they began a clinical trial and put it into humans.



Okay, so the point of that--I mean, there are a number of points in that whole story about manipulating virulence. One is, virulence can evolve really quick. Virulence has been manipulated by medical technology, for the last fifty years, to produce some of the most successful vaccines on the planet.



That itself is an impressive confirmation of this hypothesis, that I've just put up there, which is that in order to do really well on one host, you have to give up the ability to infect others. So if you want to produce a vaccine that's a live, attenuated vaccine, that infects a human, you take it out of the human, you put it into something else; you make it really good at killing that other thing; it becomes lousy at killing humans, and when it gets lousy enough at killing humans, you can use it as a live vaccine.



Now there's one more thing I want to tell you about evolutionary medicine, and that's about whether virulence will evolve in response to vaccines. So I've already introduced you to the virulence transmission tradeoff. If you're too virulent, you won't transmit, because you will have killed your host before you can get out. Okay?



This is supposed to be the most fundamental tradeoff shaping virulence evolution. It's thought to be widespread, and it really is thought to drive virulence to an intermediate level. There's quite a bit of evidence indicating that this is, broadly speaking, true. Okay?



Now what happens when you make an imperfect vaccine? It does pretty well, but it doesn't kill all of the pathogens in all of the hosts. Okay? That's why we call it imperfect. Well that imperfect vaccine will reduce the cost of virulence by making likely that some hosts will survive in the presence of virulent strains. So you're getting a partial immune response. The pathogen can persist in the body, a longer period of time; because, after all, the vaccine is working a bit.



But then if the virulent strains are the more competitive ones, and you've got multiple infection, then the virulent strains are the ones that are going to be surviving the longest in the bodies of people that have an imperfect response to the vaccine. Okay? So it turns out that this actually happens in mice with malaria; you can demonstrate with mouse malaria that this is the case. And the Gates Foundation and WHO would like to vaccinate 500 million humans against malaria. All of the malaria vaccines are imperfect; as a matter of fact, there isn't one that's really very good at all yet, but it looks like all the malaria vaccines will be imperfect.



And that really creates an ethical or public health dilemma, which is rather similar to antibiotic resistance. It's going to be really good for the individual human being to be vaccinated against malaria. Hundreds of millions of lives would probably be saved. But, as an unfortunate byproduct of this wonderful thing, we are probably going to have a situation in which the surviving disease becomes more virulent, and a few people are then hit by a really nasty strain of malaria.



So, as with antibiotic resistance, it's probably a good thing to know, that this might happen, so that you can start getting ready for it. It's not a recommendation that you don't vaccinate, it's a recommendation that you understand the consequences of vaccination, which are evolutionary, and be prepared to deal with them. So if you're interested in this particular thing, I've listed authors that you can search on.



So the take-home on evolutionary medicine basically is that evolutionary thinking actually provides some interesting new illuminations of problems in both medical research and practice. But it certainly doesn't eliminate, or replace, all of that other important insight that we've gotten from molecular medicine, and basically from evidence-based scientific medicine, up to this point. There's just a tremendous amount in physiology and genetics and biochemistry which is absolutely essential to know. This, however, also is something that is important to know. Okay, see you tonight, if you're coming.



[end of transcript]