Hopi Hoekstra (Harvard University) Part 2: Genetics of Morphology

Hi, my name is Hopi Hoekstra and I’m a professor at Harvard University. And in this second segment, what I would like to do is tell you a story about the genetic basis of evolutionary change. And in particular, we’re going to focus on the story of a morphological trait. I’m going to tell you this story in the context of making links between environment, phenotype, and genotype. In particular, I’m going to tell you today a three-part story. The first part of the story, I’m going to tell you about a role for natural selection in driving differences and traits in a natural population. And then I’m going to take you from the field into the lab, where we’ve been doing work to understand the genetic basis or the genes that control this phenotypic difference. And it’s not just that we want to know the genes, but I’ll tell you about how changes in these genes through development actually produce variations in the phenotype. And then once we made all the links, then we’ll have a more complete understanding of the process of adaptation. And here’s where I think things can get really fun. Because we can go back out into the wild and ask how these traits evolved in natural populations. So let’s start today at the level of phenotype. So the phenotype I’m going to tell you about is one that we’ve been studying in my group for almost a decade. And that is color variation. So why do we study color? Well, color is one of the primary ways in which organisms interact with their environment. And it varies tremendously between species, and it can also vary between species. And in particular, we know at least in some cases, even small changes in color difference can have a huge impact on fitness. The ability of organisms to reproduce and survive in the wild. So here I’ve just given you a number of examples of how color is used. It can be used, for example, in terms of reproduction in that it can be used for mate choice. So we have the canonical example of the peacock’s tail. But flowers also use color to attract pollinators which is the way that they reproduce. Color can also be used not to attract other species or other individuals, but it can be a way to warn them of let’s say a distasteful poison. As is the case in these poison frogs. Now, no good biological story comes without having cheaters. So we also have mimics, those species that are themselves not toxic, but mimic those that are toxic. And thereby are also avoided by predators. But by far, color is used most commonly in terms of camouflage or in terms of crypsis. So that’s what I’m going to focus on today. In addition to being ecologically relevant, the other reason we study color is because we can rely on nearly a decade’s worth of work by geneticists who have been tracking down genes involved in spontaneous mutations that occur in laboratory populations of mice. So here what I’ve done is I’ve made a list, which again I don’t expect you to read, but just to appreciate that we know a lot of genes. And if you mutate that gene, it’s going to have an effect on color. And here are some of the mutant color differences that have spontaneously arose in laboratory colonies of mice. So in some sense, we have a little bit of a headstart because we know a number of what I’ll refer to as candidate genes, genes that contribute to color differences in mammals, but may also contribute to natural variation in color. Now unfortunately, laboratory mice or their wild equivalents, while very common in nature, for example, in our houses, vary a lot in laboratory populations. They don’t actually vary that much in the wild. So, instead of studying these mice, we’ve decided to do a study on a closely related group of mice, mice in the genus peromyscus called deer mice, shown here in their slightly flattened form. So this is a common way that mice are kept in museum collections. And it nicely illustrates the variation in color that I’m going to talk about today. So in this first image, you can see that these deer mice vary tremendously in their dorsal coat. They vary from almost completely white to almost completely black. But they also vary not just in the pigments and individual hairs on their dorsal coat, but they also differ in the distribution of pigments across the body. Or variation in color pattern, as shown here. So these candidate genes that I showed you in the previous slide, many of those are implicated in variation in dorsal color. But in fact, we know very little about how patterns are made. So by studying these mice, not only can we take advantage of this vast range of variation in the color, but we also may learn something new about color patterning. So you may have already noticed that these slides were both taken by someone called Sumner back in the 1920’s. Well, this is Francis Sumner, shown here. In his field regalia. This is actually the outfit that he would wear when he would go out into the wild and trap mice. He’s a classic natural historian, he was associated with initially the University of Michigan natural history museum. And he spent a bulk of his career trying to answer the question of why populations vary so much in nature. And to do this, he would drive around the U.S. and catch mice, and document variation in a number of traits, including color variation. So Francis Sumner’s favorite species of deer mouse, and mine as well, is a particular species call peromyscus polionotus. Peromyscus polionotus is often referred to as the old field mouse. And that’s because much of its range in the southeastern U.S., as seen here, so Alabama, Georgia, South Carolina, and Northern Florida. It occurs in these old fields, which are really overgrown agricultural fields. Now throughout most of its range, it may look to you like a typical mouse. It’s got a dark brown coat, a gray scruffy belly, and a striped tail. But what’s particularly interesting to us about these mice is that they’ve recently invaded these sandbar islands and sandy dune habitats on the Gulf coast of Florida, as well as the Atlantic coast of Florida. So each one of these numbers on this map refers to a different subspecies of what I’ll refer to as “beach mice,” because the mice actually live on the beach. Now, the first part of the story, I’m going to focus on one of these subspecies. Here number 3. And that is the Santa Rosa Island beach mouse. So let me show you a picture of their habitat. So unlike their mainland counterparts that live in dark loamy soils, these mice live on these beautiful sandy islands off the Gulf coast of Florida. And here’s a picture of one of our field sites. So you’ll notice that there are two dramatic differences in habitat that these mice occupy. So first, you can tell that the soil, in this case, this granulated sand that’s almost like walking on hills of granulated sugar. It’s much lighter in color than the dark loamy soils of the mainland subspecies. But in addition, these beach habitats also have much less vegetative cover, so these mice are exposed to really high levels of predation. And I’ll tell you more about their predators in a minute. So it may not be surprising then, when we go out and catch mice in these beautiful beaches, the mice look different. So here’s a picture of one of those beach mice. And I should mention that this is not to scale. So both of these mice are about the same size and they’re about the size of a ping pong ball. But what this slide does serve to illustrate is the dramatic differences in pigmentation. So this particular mouse, you can see is lacking pigment on its nose,
on its sides, and if you could see the tail, it’s also missing that strong tail stripe. The other thing I want to mention to you about this system is that we know something about the geological age of these islands. They’re about 6000 years old, which suggests that the difference in coat color that you see here may have evolved in just a few thousand years. So you may all be thinking that this makes perfect sense, right? That these mice are running around in these beautiful white sand beaches and having a light color coat would make them more camouflaged. And that’s a great idea, but we wanted to actually prove that. So as scientists, what we wanted to do is empirically demonstrate that color matters for survival. So actually do an experiment. We wanted to know how much it matters, in other words, we want to estimate the strength of selection. How favorable is it to actually match the background? And then finally, we wanted to know the agent of selection. Who’s doing the selection? And in this case, who are the predators? So first I want to tell you about the experiments we did to try to make this link between color variation and the differences in environment that these mice live in. And in particular, implicate a role for natural selection. Now if I could do any experiment in the world, here’s what I’d love to do. I’d love to catch let’s say 100 light mice and 100 dark mice, maybe give them all a tag. And let’s say release half of them, equal numbers of light and dark, in dark habitat. The other half, equal numbers of light and dark, in light habitat. And then come back, let’s say a few months later, and see who survived. And I’d have the expectation that mice that are lighter would survive better in light habitat, and those that are darker in dark habitat. Now for a number of reasons, that experiment is quite hard to do. So instead, what we did is what I’d argue is the next best experiment. And in some ways, it may be even better. So here’s the experiment that we actually did. Instead of using live mice, we made mice. So here’s a picture of my postdoc, Sacha Vignieri, who along with an undergraduate from Harvard, Joanna Larson, made hundreds of plasticine mice. Half of them were painted dark to mimic the mainland mice, and half of them were painted light to mimic the beach mice. Now this experiment in some ways, as I mentioned may even be better than using live mice, because here the only difference in these mice is their color. So they’re made from the same mold, they all look the same, they all smell the same. Whereas with live mice, the beach mice and mainland mice may differ in let’s say smell, in escape behavior, in activity patterns. So here, the experiment completely focuses on the difference in color and not correlated traits. But the downside of this experiment is would it actually work? Could we actually fool predators into attacking these plasticine models of mice and not live mice? Well, I wouldn’t be telling you about this experiment if it didn’t actually work. So what Sacha did was she released equal numbers of these light and dark mice in both light and dark habitats, where live mice of the species actually occurred. And then counted predation events. So here’s a predation event. So what you’re looking at here is a dark mouse that was put out on light soil. And you may notice that it’s missing part of its left ear, and it’s got a big chunk taken out of its back. And this is a classic predation event, and in fact, not only can we tell it’s been attacked, but we can actually say something about who’s doing the attacking. Because these marks are consistent with an avian predator. So here’s the results of the larger experiment that Sacha did, where she was counting the number of predation events in different habitat types. So, what you’re looking at here are the results of this experiment. So let’s first focus on this far panel at the light habitat. What you can see is that there’s cryptic and what we’ll refer to as non-cryptic mice. And these bars indicate the relative level of predation in both of these two types of mice in this particular habitat. And what you can immediately see is the level of predation here in these cryptic mice is much lower, in fact, it’s about half of non-cryptic mice. So what this means is that both mice were attacked by predators, but the mismatched mice were attacked about twice as often. Now when we look at the dark habitat we see a very similar pattern, but in reverse. Here we can see the dark mice survived much better, and while still attacked, they were attacked about half as often as the mismatched mice. So what this first thing tells us is that color seems to matter. And in fact it matters a lot. We can take these numbers and sort of translate that into a selection intensity. I’m not going to go into details about this, but let me just say that color matters a great deal for these mice. And in fact, mice that match their habitat have about a 50% increased chance of survival compared to those that are mismatched. And the final thing I want to say, as I mentioned, we can tell in some cases who’s doing the predating. And about half the attacks were due to avian predators, and about half of the attacks were due to mammalian predators like coyotes and foxes. So together, what this experiment is telling us is that the differences between color variation are tightly linked to the environment and that it’s natural selection that is playing a role in driving these color differences. So now that we’ve implicated a role for natural selection, the next thing I want to do is to take you from the field into the lab, where I’ll tell you about how we’re going about identifying the genes that are responsible for these differences in adaptive color variation. So the first thing I want to do is give you a general sense or an overview of the approach that we’re taking. And I don’t want you to get caught up in the details, but more appreciate this general approach. So what we’re able to do is take these mice from the field and bring them into the lab, so we have both dark mice and light mice. And they have differences in their genomes, in their chromosomes, so I’m going to illustrate this by the dark mice having dark chromosomes and the light mouse having light chromosomes. And what we can do is take a dark mouse and a light mouse, one male and one female. Put them in a cage together and they’ll actually reproduce. And they’ll produce what we refer to as hybrids. Then we take those hybrid individuals, and we breed them together. And then what happens is in this next generation is their genomes get shuffled. So some individuals are going to have different parts of their chromosomes that come from the light parent, and some from the dark parent. So we’re effectively shuffling up their genomes. Now in this population, this second generation of hybrids, what we do in all those individuals is we measure their coat color pattern, and then using genetics or molecular biology, we’re able to sort of characterize their chromosomes and determine what regions come from each of the parents. And then what we do is — I’ll just simplify and say we do a nice statistical analysis and ask, are there regions of the genome that seem to be correlated with different aspects of different color variation? So for example, in these chromosomes here, do all these mice that have the light allele from this parent in this region of the chromosome, if all those mice have, let’s say, light tails. That suggests that a gene controlling tail color may reside in this part of the chromosome. And this is what we refer to as a QTL analysis, or quantitative trait locus analysis. But it’s really just this simple statistical association. And then what we do with this statistical association is that we take that region of the chromosome, and we look
for its homologous region, the same region in the mouse genome, which we have the complete genome sequence. We know where all the genes are. And we look for candidate genes, remember that list of candidate genes that I showed you earlier in the talk, and ask do any of those candidate genes fall within this particular chromosome region. With the ultimate goal of finding a mutation in that gene whether it’s in the protein structure of that gene or maybe a mutation that controls the regulation of this gene, that we can then link to the color differences between the parents. So now that I’ve given you this overview, next what I want to do is walk you through each of the pieces. So as I mentioned the first thing we do is this cross. So we brought mice in from the wild, we brought in a mainland species and one of these beach mouse subspecies. And here they are, shown again in their flattened form. You can see a dark parent, and over here the light parent. And here is that F1 hybrid shown here. And you can already see this F1 hybrid has traits from both of the parents. So for example, it doesn’t have a tail stripe like the light parent but it has a fully pigmented face like the dark parent. That suggests both dominant and recessive alleles contribute to this light color adaptive beach mouse phenotype. Then as I mentioned, we take these F1 hybrids and we breed them together, and that’s when we get these F2s. And this is where we’ve now with recombination shuffled up their genomes. So, for example, presumably this mouse has more pigment alleles from the light parent, and the mouse over here has more pigment alleles from the dark parent. But what you can see is that there’s a continuum of variation. And what this immediately tells us that this color difference we observe between beach mice and mainland mice is not controlled by a single gene, but in fact is controlled by a handful of genes. And the reason I say a handful and not hundreds is because you can see in this population we get mice that look like the dark parent, and we get mice that look like the light parent. And this suggests there are not hundreds of genes, because it would be a very small chance that we would get all the light — all hundred of those light alleles in one individual. But instead, probably just a handful. And from this variation, we estimate there are about 3-5 genes. But I’ll tell you more about those genes in just a minute. So as I mentioned, we then take the color variation in these mice and we measure them in all these individuals. And then we also genotype them to figure out what regions of the genome come from the light and dark parent. We did this using molecular techniques. And here’s the results of that. So what this is is each one of those lines shown here represents a chromosome. And each one of these markers is a difference between the light and the dark parent. So in each one of these markers we can tell whether a particular individual has that region of the genome comes from the dark parent or the light parent. Then what we do is the statistical analysis. And what we found was, there are three regions of the genome, which I’ve highlighted here, that seem to control color. That is there’s genes in these regions of the genome that control different aspects of color patterning. And lucky for us, in each one of these regions, there’s one of these candidate genes that I mentioned earlier. Oh, I should also mention that the differences in the size of the arrows reflects the amount of variation that a particular locus explains. So the Agouti locus way over here, explains a larger proportion of variation compared to Corin, which explains the smallest amount. So what this is telling us is that there’s 3 regions of the genome, and each one of those contains what I’ll refer to as a candidate gene. So next what I’d like to do is just tell you about what of these genes. And then I’ll summarize and tell you about all three of them at the end. So the gene I’m going to focus on is this gene up here, Mc1r, or the melanocortin 1 receptor. And one of the reasons we focused on this gene is because we actually know a lot about the structure and the function of this gene. So, the melanocortin receptor is a classic g-protein coupled receptor. That is, it’s found in the membrane, and it’s got extracellular and intracellular regions. Each one of these little circles represents a different amino acid, and what I’ve done is I’ve color coded those amino acids that we know when you change that amino acid, it has an effect on color, and on particular species. And those that make — when you make that change, an individual darker, it’s shown in black and those lighter is shown in gray. So you can see summarized over a number of different studies, that there are multiple mutations in this receptor that can affect color. And it can either make an individual lighter or darker. So the first thing to note is that there are many different mutations. The second thing to note is that they’re found throughout the receptor. And the third thing to note is that even a single amino acid mutation can have an effect on color. So one change can have a big effect on phenotype. Now, the first thing we did is we sequenced this gene in both the mainland and the beach form, and asked are there mutational differences between the two? And in fact, we found one and it’s highlighted here in red. And the mutation is a single nucleotide change that caused the change in amino acid, whereas the mainland species had an arginine at position 65, beach mice had a cysteine. And this is a charged changing mutation, so it actually changed the charge of that amino acid so that it’s more likely to have an effect on the structure and function of melanocortin 1 receptor. Now the unfortunate thing, though, was that it didn’t overlap with any of the other mutations that had been previously characterized in other species. But that’s okay because we can do an experiment to test whether this mutational change had an effect on the way that this receptor functions. So first thing I want to do is tell you a little bit about what this receptor does. And then I’ll tell you about our experiment. So what I’m showing you here is a melanocyte. Now a melanocyte is a pigmentation producing cell. And in mammals, we produce two types of pigment, a dark brown to black eumelanin, and a yellow to blonde pheomelanin. So you can look at your own hair and determine whether you have eumelanin or you have pheomelanin. Now, this melanocyte has the ability to produce both types of pigments. But which pigment it produces at any one time is largely controlled by the melanocortin-1 receptor. Which essentially acts like a switch. When it’s turned on, that is when let’s say alpha-MSH, which activates Mc1r, is around, Mc1r turns on and it signals by increasing intracellular cyclic AMP levels, and you get the production of dark pigment. By contrast, when Mc1r is turned off, then you get the production of less cyclic AMP intracellularly, and the result is light pigment. So Mc1r is very much a switch that determines which pigment is produced. Now this leads to a nice prediction. So in beach mice we have a mutation in Mc1r that we think leads to light coloration. So our prediction is this, is that mutation of arginine to cysteine change at position 65 will reduce receptor activity, which will result in lighter pigmentation. So we can test this doing an experiment. And so what we did is we took both the light allele and the dark allele, that remember, differs by one nucleotide change, we cloned it into an expression vector, we put it into cells. And then we added alpha-MSH in increasing amounts. To activate Mc1r, and then as a proxy for activity, we measured cyclic AMP. So here are the results of this experiment. So here what we did is you can see we added increasing amounts of alpha-MSH, which turned on Mc1r, and you can see that its signaling higher and higher cyclic AMP until it sort of plateaus out. And this is a normal sigmoidal response curve that we see in the mainland mouse. Now when we did the same experiment with the beach mouse allele that differs by again that one nucleotide change, what you can see is there’s a dramatically different pattern of activity. And that is no matter how much alpha-MSH we added, there’s still a relatively low level of receptor activity. So what this suggests is that one nucleotide change changes the function of the receptor, and it’s in the direction we expect. That it has lower activity, which is consistent with producing lighter pigmentation. So at this point, it’s worthwhile stepping back and sort of thinking about what I’ve just showed you. So here I’ve showed you a single nucleotide change affects the activity of the receptor, we know this receptor affects color variation, and we know that color variation affects survival in the wild. So what we have done here is made a link between a single nucleotide change and fitness or survival in the wild. But I don’t want to leave you with the impression that this is the whole story, because as I mentioned, color difference is controlled not by a single gene, but by multiple genes. And so the two other genes, if you are paying attention you might have noticed, actually interact with Mc1r. So Agouti, for example, represses Mc1r activity. And what we see in beach mice, is that higher levels of Agouti expression are associated with lighter pigmentation. And so the allele in beach mice has increased expression of Agouti, which leads to lower activity of Mc1r and light pigment. Corin is the third gene, and while this gene is just newly discovered in the last few years. We don’t know its exact function but we know it interacts with Agouti, and again, increased expression of Corin is associated with this light pigmentation in beach mice. So these genes are interacting together to produce light pigmentation. So what we’ve done in this second part is to tell you about the genes that affect coloration and a little bit about how changes in those genes actually cause these differences in color patterning. And now that we have a much more complete picture of adaptation, here’s where I think things can get really fun. So I’m going to take you now back from the lab into the wild. And we’re going to talk about how these traits may have evolved in natural populations of beach mice. So to do this, this involves us actually going back to the field. So here’s a picture of me and my postdoc, Vera Domingues, when we’re out on the Atlantic coast catching mice. Here’s a mouse currently being weighed. So we hang it by its tail on a little pesola. We take measurements including their weight, the size of their ears and feet, et cetera. And what Vera’s doing here is measuring their coat color. And what’s nice about this work in the wild is we take these measurements, we measure their coat color, we also give them a little ear tag, and we take a little snippet of DNA from their tail, and we release them back in the wild. So here we have a DNA sample from each of these mice and we have a record of their coloration. So next what I’d like to do is tell you about what we’ve learned about natural populations of these mice and how these color differences may have evolved. So just by way of reminder, so far what I’ve done is I’ve focused on only one of these populations, that is population number 3, the Santa Rosa Island beach mouse. But next what I’d like to do is tell you about variation among these subspecies. So the five subspecies on the Gulf coast and the three subspecies on the Atlantic coast. So, when we go out and catch these mice and record their color differences. We find some very striking patterns, which I’m going to show you in the next slide. So here what I’m showing you are cartoons that represent the different subspecies of beach mice. So each one of these cartoons shows you the typical color of a beach mouse from each of these populations, compared here to a mainland mouse. So the first thing you may notice is that all the beach mice are much lighter in color compared to the mainland mouse. But that each of these subspecies differs in their color pattern, and in fact, they’re so distinct that if you went for let’s say spring break down to the Gulf coast of Florida and you brought me back a beach mouse, I would say with about 95% certainty just by looking at the color of the beach mouse, I could tell you what subspecies it is. But, instead if you went to Florida and you didn’t tell me if you went to the Atlantic coast or the Gulf coast, and you just brought me back a beach mouse, I’d probably have a 50/50 chance of knowing what subspecies it was and that’s because the mice on the Atlantic coast are very similar to mice on the Gulf coast. So let me highlight that here. So for example, these two subspecies, even though they’re separated by over 300 kilometers, are very similar in their overall color pattern. And in fact, I can’t tell them apart. Likewise, these mice are very similar. And these mice are very similar. So what this suggests is that on the Atlantic coast and Gulf coast, the mice have convergent color patterns. And so what we wanted to do first was ask the question, did these mice evolve these similar color differences independently? And if so, did they use the same genes? So the first thing I want to show you is a tree, or a topology that shows you the relationships among these different subspecies. So this is a simplified version of a tree that we generated using molecular data, but it highlights the relationships among these subspecies within peromyscus polionotus. And what you can see is the Gulf coast beach mice, shown here, all five of those subspecies cluster together. They’re very closely related. But they’re actually not that closely related to Atlantic coast beach mice, shown here. In other words, it looks like light coloration has evolved independently on two coasts. So the Gulf coast beach mice probably arose from a dark colored ancestor sometime in the past, that was probably from the Panhandle of Florida. Whereas, the Atlantic coast beach mice independently evolved light coloration, probably from an ancestor in Central Florida that was dark in color. Okay, but here’s the cool part, now that we now at least in one of these Gulf coast subspecies that the melanocortin-1 receptor is involved, we can ask in these independently evolved light colored beach mice on the Atlantic coast, is that same gene and same mutation involved? So to do this, we returned back to this melanocortin-1 gene. And we sequenced the DNA in the mice that we collected on the Atlantic coast and asked, do we find that same arginine to cysteine change at position 65? So we simply genotyped that one particular site and asked, is it present in the Atlantic coast? Now, despite the fact that mice from the Gulf coast and the Atlantic coast are so similar in coat color, let me just say that we never found that cysteine change in any of the mice from the Atlantic coast. So what that tells us is that the same mutation isn’t involved in that convergently evolved light coloration on the Atlantic coast. So you may be thinking, well, it’s not the same mutation, but maybe it’s a new mutation. Remember there’s lots of mutations in Mc1r that can cause color differences, I told you this earlier. So maybe a new mutation in Mc1r is causing light coloration on the Atlantic coast. So it may not be the same mutation, but it could be the same gene. So we went back to the Atlantic coast mice and sequenced the entire melanocortin-1 receptor, and asked are there any new mutations that are correlated with color. Well, in fact, we found four new mutations in the melanocortin-1 receptor. But none of them were perfectly correlated with color, and when we did those pharmacological assays like the ones I showed you earlier, none of them had an effect on the activity of Mc1r. So what this tells us is that it’s not just the same mutation, it’s also not the same gene that’s responsible for the convergent evolution of light coloration in the Atlantic coast mice. So this is the case for melanocortin-1 receptor, but we’re still checking these populations for changes in Agouti and Corin. So what I’ve done today is I’ve told you a story about how identifying not only the ultimate causes of phenotypic variation, but also the genetic causes can tell us something about how traits evolved in the wild. And this story revolved around a single species, in which different mutations, at least in regards to the melanocortin-1 receptor, are involved in generating similar coat color patterns on two coasts of Florida. But I want to end by telling you a story about convergent evolution. Because sometimes the same genes and same mutations are involved in similar phenotypes in very different organisms. So, if you think about mammals, think about what is the most different mammal from a mouse. Often the answer I get is an elephant, and it’s close. I’m going to tell you a story about mammoths. So, mammoths were the subject of intense study, especially about five years ago when there was a big interest in sequencing ancient DNA. And mammoths were a great target because they occurred in Siberia, and their DNA was essentially frozen in permafrost about 14,000 years ago. So this is almost like keeping DNA in a giant freezer, which is the best conditions possible. So about five years ago, the goal was to sequence an entire gene from an extinct organism. Now today of course, we’re sequencing entire genomes of extinct organisms, but just five years ago, we wanted to sequence an entire gene from the nuclear genome. So this is what a group in Germany, in Leipzig, headed by Michael Hofreiter did. And the gene they chose to study was the melanocortin-1 receptor, because it’s a very simple gene. Remember I told you, we know a lot about its structure function, it’s only about 1,000 base pairs in length, and there’s no introns. So it’s very simple and it’s a great starting point. So they sequenced the melanocortin-1 receptor, in DNA extracted from mammoths. And here’s what they found. They found a mutation, and what mutation was it? Well, it was an arginine to cysteine change at the exact same position that we found in beach mice. Now of course the DNA it was extracted from was bone, so they didn’t know the phenotype or the coat color of mammoths, but based on our work in beach mice, what this suggests is that mammoths like beach mice, may have been polymorphic in color. Now the question of why they were polymorphic in color, we don’t know the answer to. This could be due to survival differences, other suggested that it’s due to sexual selection. So when this work was published, the press line was that blonde mammoths have more fun. But I’m not going to give you any explanation, I’ll leave that up to your imagination. So in this case, we have very divergent organisms, mice and mammoths that use not only the same gene, but the same mutation. And in fact, as I alluded to earlier, melanocortin-1 receptor is involved in a number of different color variants. And a number of organisms that you may be familiar with. So in this case, it was the same mutation, but we know that other changes in the melanocortin receptor can also cause differences in color through different mutations. So I just wanted to give you some examples. So some work that I’ve been doing with a colleague at UC Berkeley, Erica Rosenblum, shows that changes in the melanocortin-1 receptor is responsible for the production of these very adorable lizards that differ in color, when they occur in White Sands, New Mexico. So you can guess which lizard occurs on white sands and which one occurs off white sands. Color differences are also involved in animals you may see every day, including cows. Also, many of you may know of or even have a labrador dog. Well, they come in generally two colors, there’s the black labs and blonde labs, again this is caused by a change in the melanocortin-1 receptor. And much more recently, again work out of Germany, this time Svante Paabo’s group, has shown that color changes in the melanocortin receptor, in addition to being responsible for human color differences, may also be responsible for color differences or hair differences in neanderthals. So they showed that changes in the melanocortin-1 receptor or variants in the melanocortin-1 receptor were found in neanderthals, suggesting even back in those days, there could have been redheads as well. So what I hope to have done today is to suggest to you that by making the link between environment, phenotype — in this case a morphological trait, and genotype, we’re able to say something about how organisms evolve in the wild. The work that I presented today was done by a large number of people. These are some of the people in my lab group that contributed to the work, shown here looking their mousiest. And in particular, the work I talked about today was done by folks like Cynthia Steiner, Marie Manceau, Vera Domingues, Sacha Vignieri, Holger Rompler, and Lynne Mullen, as well as an undergraduate, Joanna Larson. And we were funded by a number of sources shown here, as well. And with that, thank you for your attention. I hope you enjoyed this segment, and you’ll stick around for segment three. Thank you very much.

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4 Responses

  1. PipyHunter says:

    I wanted to watch only first part but it was too lovely so I've watched this as well.

  2. lindosland says:

    I wonder whether there is any evidence that the observed change from argenine to cystine is the actual cause of colour change, or whether it could just be an accidental marker for another change that happened in that line of descent, such as in the control region or even a change that altered epigenetics (I note that what mice are fed on can change their colour epigenetically.)  Can you say that the whole gene sequence (whatever that is – how do you define your gene) is the same except for that one mutation? Interesting that the gene you chose has no introns – most animal genes have introns don't they?

  3. lindosland says:

    You talk of 'dominant' and 'recessive' alleles, but surely these are outdated concepts – an allele is only dominant over some other alleles but may be recessive to yet others, and there are many examples of hemizygous phenotypes where a 'half dose' of a gene product produces it's own effect compared to the heterozygous form. Quantitative gene expression is surely a big factor.  Great talks and very well presented.

  4. Darun S R says:

    Awesome lecture…One day I'll join your Lab Mam..??

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