Hello, and welcome back to Introduction to Genetics in Evolution. We've been talking about the process of species formation, or speciation. This again is what leads to the biodiversity that we have on the planet. So far, we've talked about the formation of different clusters, basically what is it that makes one species genetically distinct from the others. Fundamental thesis, they do not exchange genes, or at least they do at a very, very low level. The things that prevent gene exchange are these barrier traits. We then talked about the geography of species formation. We talked about how some species are formed in geographic isolation or by allopatric speciation, and others seem to just split off. Now this would be sympatric speciation. Now we also talked about direct selection for species formation in the context of reinforcement. What we'll do now is build on all these to look at the genetic changes needed to make a new species. What is the genetic basis of speciation? Well, as I mentioned earlier, genetics of species formation is the same as the genetics of these barrier traits. Why is it that species one has a preference for this particular sound or species two has a preference for a different courtship sound? Well, it's because there's an underlying genetic basis. And by knowing the genetic differences between species that are causing these barrier traits, like this difference in courtship song that you heard. We can see the genetics of species formation. The problem we have though is there's an intrinsic contradiction that we can't do genetics between species easily because, by definition, we can't get crosses to work. So, how do we do this? Well, we get around this problem by using incompletely separated species. Now, importantly, barriers are not always perfect, right? That we can actually have a little bit of gene exchange between things we consider to be good species. And sometimes these barrier traits are actually weaker in the lab than they are out in the wild or in nature. The other thing is that when we look at hybrids, in specific whether hybrids are sterile, we sometimes see that one hybrid sex is sterile or dead. And thus we can study the genetic basis of crosses between those two parental species by using crosses to the other hybrid sex. Now, we'll focus on hybrid sterility in this particular video. Now obviously, we can study the genetic basis of any of these barrier traits and those are fundamentally important to studying speciation. But why is it that hybrids are sterile? Well, again, hybrids only have the alleles of their parental species. So a mule only has one chromosomal complement from horse and one chromosomal complement from donkey. Given that was fine in horse and given that was fine in donkey, why is it when put together, they don't work? Well, this is the question. No gene functions to cause sterility. There is no sterility gene in that the normal function of this gene is to cause sterility. Obviously if the gene's function was to cause sterility, then the species wouldn't exist. But it's more likely what's happening is we are having disruptions of the normal function, specifically in hybrids, and that's why we see hybrid sterility. It's thought that the interactions that are causing hybrid sterility are from alleles from one species with alleles from the other because otherwise you would see sterility within species as well. So what we can do is we can try to map hybrid sterility within the genome through QTL mapping, just like we discussed it before. It's a little bit of a tricky trait, because it's something that you should only find with this interaction between some genetic material from species one and some genetic material from species two, okay? So it's a little bit funny in that regard. Now one important thing to consider here is that single gene speciation is probably not the answer, at least not very common. Now imagine a situation where the heterozygotes are sterile. So let's start up an ancestry population where everybody's AA. And let's say that Aa is sterile. Well we have the first mutation to a occurs, so here's an individual who's Aa. Well, what's gonna happen? Well we said this individual's sterile so, [SOUND] gone. [LAUGH] So, you can see there's a problem with single gene speciation. If you just have a single mutation that leads to this other form, and since it will always arise in a hybrid, you can't have two simultaneous mutations to a that come together. You can't actually get this. This is the problem referred to as underdominance. We saw this before, right, that selection will always favor the loss of the rare allele. We talked about this in the context of natural selection earlier when we looked at different forms of natural selection. So, the workaround is to look at epistasis or interactions between two or more loci. So let's imagine that the A allele interacts with the B allele to cause hybrid sterility when the ancestry have neither. You have aa bb. Everybody's happy. Now let's say in one species you evolve, you have a change to A. This is still okay because again, A only interacts with B to cause sterility. So this species is fine. And this other species, you have a mutation to B that then spreads. So again, everybody here is aa BB, again, everybody's fine. What happens in the hybrid? Well, in the hybrid, you bring together the A with the B, and therefore you have hybrid sterility. Now, you might think, well, why does this happen? Well, you can think of it as two components of a sperm tail that just don't fit together, just as an example. So this model for hybrid sterility has been referred to as the Dobzhansky-Muller model because it was introduced by the two of them. So this is the workaround against this underdominance problem, and it's thought that this is the kind of interaction that may be associated with a lot of hybrid sterility that we see out there. This is the kind of junction we expect. Now, one big observation that has come in looking at species hybrids in general and looking at whether or not the hybrids are sterile or not is that when one hybrid sex. If just one of the two hybrid sexes is sterile or inviable, it tends to be the XY sex. Notice I say the XY sex. So in mammals, that would be the males. Fruit flies, that would also be the males. In birds and butterflies, XY, or there they call them ZW, the heterogametic sex is actually the females. And there you tend to see that the females are the ones that are sterile if one hybrid sex is. This is referred to as Haldane's rule, because it was identified first by JBS Haldane, and in fact it is one of the most consistent rules in evolutionary biology. That very, very often, and only with few exceptions, if one hybrid sex is sterile or unviable, it's almost always the XY sex. Now, although this pattern has been known for nearly 100 years, the explanation was only deciphered within the past 20 years. And there's two parts to it. First, as you would imagine of course, sex-chromosomes must play a role in this because there has to be something associated with the XY part. But the other aspect is combining it with the Dobzhansky-Muller model that we saw. There is 2-locus epistasis involving at least one gene on the X-chromosome and one gene on an autosome. I'm sorry, the X-chromosomal one is often recessive as well. That this interaction seems to be what's associated with hybrid sterility. And when you put it together, that fully explains why the XY sex would tend to be sterile. So I'm not going to go into that in detail but I just wanted to introduce that to you. Now where this has been identified is through the workhorses of genetics. These are Drosophila fruit flies. There are tons and tons of species out there, including many recently diverged species. We have genome sequences for them. They're very easy to rear and cross. And as a result of that, there have been extensive, extensive studies of the genetic basis of hybrid sterility among Drosophila species. Such as between Drosophila simulans and sechellia, between Drosophila pseudoobscura and persimilis, between a lot of these Drosophilas. It's because they're so easy to work with. Now in doing this, one of the conclusions is that there is extensive evidence for natural selection involved in the genes that are associated with hybrid male sterility in Drosophila. And when we look at the underlying genes that are causing hybrid sterility or hybrid inviability, and we apply tests of selection. As you've seen in the McDonald-Kreitman test that we discussed earlier, we see a strong signature of directional or positive selection. So when we look at again at this ratio of nonsynonymous to synonymous within versus between species, we see the ratio is much higher between species than it is within species. And that's indicative of this directional positive selection. In this case it's highly statistically significant. So this is the example from Nup96 which causes hybrid inviability in crosses between Drosophila melanogaster and Drosophila simulans. Now you may be wondering, why is it you have this natural selection? Why did natural selection cause these genes to change in a way such as to make the hybrid sterile? Well we already talked about how you can't have selection directly favoring hybrid sterility cuz it's too late. You've already made the hybrid. So this can't be reinforcing selection. This is not going to be a direct effective selection. But it should be something incidental. So what is it selection was actually favoring? Well one possibility is fertilization. So you've had very strong selection for fertilization competitiveness. Remember when we talked about the DNDS test and the McDonald-Kreitman test? One of the categories of genes that evolved the fastest under the strongest positive selection are those involved in fertilization. Now, because part of this is that females from many species will mate multiple times, you have this sperm competition going on. And you want your sperm to be the best at fertilizing even in a competitive scenario. This will potentially cause rapid evolutionary change and very, very strong selection. And a potential outcome of this are that some of these changes incidentally cause sterility in hybrids. There's no cost to this because the sterility is in hybrids. It's not within species. Selection's only focused on what's going on within species so this is thought to be one of the potential forces driving this rapid evolutionary change. Overall we'll have to say that Darwin was right. So here's a couple quotes from his famous book. Hybrid sterility is not a specially endowed quality but is incidental on other acquired differences. That seems right. And is caused by a hybrid's organization having been disturbed by two organizations having been compounded into one. Again, natural selection appears to be a major contributor, so he's good, he's right. This is true for hybrid sterility, this is also true for a lot of other barrier traits out there. So, let me recap very quickly. Sterility is often a result from an interaction between genes on the X and genes on the autosomes. So autosomes are the other chromosomes besides the X and Y chromosome. Recessitivity of genes on the Xs is what creates this Haldane's rule. I didn't go into that in detail, but I just mentioned that to you in passing. And importantly, natural selection seems to be involved in driving these gene forms. So overall we've talked about speciation in a lot of ways. We've talked about why these clusters didn't fuse because of these barrier traits and why we don't see intermediates. We talked about the importance of geography and how we can use geography for interpreting the processes driving species. And we talked very briefly about the genetic basis of species formation. Now, there are several implications to all this. Now, as you all know there's been a lot of human-induced habitat destruction out there. And as a result, direct result of that, the number of species worldwide has gone down dramatically. We've seen more extensive loss of species just recently than people have seen in many of those huge calamities that have happened on the earth. This is bad for humans, too. And we may like to think, whatever the, we don't need those species. But it's bad for humans too because it's increasing our vulnerability to flood and drought. It's increasing crop failure. It's increasing the spread of disease, we have more water contamination. Now, importantly, about this sort of research we're looking at the other end of the process. So extinction is the end here of what humans are creating extensively, but understanding how species form lets us have some idea of the input to this process. Unfortunately, not only are we losing existing species, but we're actually losing species that are just beginning to form. So if you look out here in Lake Victoria there's been a lot of eutrophication, basically a lot of nutrients dumped into the water as a result of human activities. This makes the water a lot more cloudy, or turbid. Now there are these fish there, these Lake Victoria cichlids. They choose their mates based on coloration. Since it's so cloudy now they actually are not as good at choosing their own type. That they actually are breeding closer to random because they just can't tell anymore. So what's happening is we're starting to see a lot more hybridization between species. These are things that were starting to form into new species, and now they're sort of collapsing back together. So there are some species that potentially would have formed that now won't. So not only are we killing off a lot of species, but we're turning down the faucet on the formation of some new species as well. Food for thought. I hope you all enjoyed this set of videos on speciation. Thank you for your time.
