Genetic Recombination And Gene Mapping

Hi. It's Mr. Andersen and in this video I'm going to talk about genetic recombination and gene mapping. And it centers on the work of Thomas Hunt Morgan who used fruit flies to show that genes just don't travel by themselves. They actually travel on chromosomes. And as those chromosomes undergo what's called crossing over, genes from one chromosome are actually going to swap position with genes from another chromosome. And so before we get to that we should talk about fruit fly genetics for just a second. And so on the left we have a wild fruit fly. That's what they normally look like. And on the right is a mutant. There are two mutations in the one the right. Now only coloration, but you can see that it also has these really small what are called vestigial wings. And so if we look at the genotypes, the one on the right is little b little b. So it has that black coloration. The one on the left we simply add a plus to it. And that implies that it's of the wild type. We could also look at vestigial wings. Maybe the genotype of the one on the left has one of the wild type normal wings but it has one of the vestigial genes. It still has normal wings on the left. And that's because the wild type is going to be dominant in this case. And so let me show you the quintessential cross that Morgan did that was so puzzling. And so what he has is a normal wild type on the left, but it's hybrid for both of these genes. And so you can think of this as like a F1 generation. And then he's simply doing a test cross with it. So he's crossing it with a mutant fly that is mutant and homozygous recessive for both of those traits. And so Morgan understood the work of Mendel and so he set up his Punnett square like this. And so on the top he's going to show all the possible gametes that we could get from this one parent. So you could have both of the wild type genes. Or you could have both those recessive mutant genes. Or you could a combination of the two. So we could have one wild one recessive. Or vice versa. Now this parent over here only can give its recessive genes and so we could represent that on the other side like this. And so he knew that there are only four possibilities that we could get out of this. And those first two are going to look like that. And we call those what are called the parental phenotypes. Why is that? Because this one looks like that parent and this one looks like that parent. In other words there's no recombination. But on these other two alternatives right here and right here, what we're getting is a recombination of those parents and so we call these simply the recombinant phenotypes. But that shouldn't have been confusing to him. If we look at the Punnett square, we have four different squares and so we would expect that 50 percent are going to be parental and 50 percent are going to recombinants. But when he did this cross what he found is that there is actually 17 percent recombinants and 83 percent that were of the parental type. And so was Mendel wrong? Was all of this wrong? No. It's just that the model wasn't good enough. And so he thought about this idea of 17% and what it meant for a really, really long time. And then finally one of his students Alfred Sturtevant, and I couldn't find a good open source picture of him, but he's always smoking a pipe, so we'll say this represents Alfred Sturtevant. One night he just blows off his homework and he figures it out. The whole thing. He figures it out. To understand it you really have to understand what's going on during meiosis. And so if we look at these two parents, so this is the double mutant on this side and this is the hybrid on the other side, let's look at each of those and figure out what gametes could they produce? And so if we look at the one on the right, we know that it can only produce these two gametes. But since we're seeing a frequency of recombination that's less than 50 percent, that implies that these two genes are found on the same chromosome. We know this now. Thomas Hunt Morgan and Alfred Sturtevant had to kind of work through this. But if we look at what does that mean? These two genes are found on the same exact chromosome. So if we go through all the steps of meiosis, remember what happens first during interphase is that we copy all of the DNA. And then it divides in half and then it divides in half again. And since those genes are on the same chromosome, I see just one possible gamete that could be produced. In other words you're going to get one of each of those recessive genes. Now let's look at that hybrid parent. And we know and Thomas Hunt Morgan knew since he saw some of those recombinants we had to have all four of these possible gametes. And so let's put the dominant or the wild type genes on this one chromosome. And the recessive on another. So how do I know that I have both of the wild type on one chromosome and both of the recessive on another? Remember this is the F1 generation. And so it's receiving this chromosome from a parent that was pure for both of these genes and vice versa for the pure mutant parent as well. And so let's go through the steps of meiosis again. And so what happens during interphase is that we copy them. Then there's one division and then there's another division. And so how many gametes do you see? Well this one is exactly the same as that one. And it's not based on orientation of the chromosomes because again they're both found on the same chromosome. And so this was puzzling. But then eventually they settled on this idea of crossing over. What if there were crossing over between these chromosomes? What if somehow this chromosome wrapped around this chromosome during meiosis? And they could see that under the microscope. They could see this occurring. If these crossed over what you could get is bits of this chromosome actually being crossed over to that one. And so what we could now produce is a chromosome that has the wild type for coloration but it has the recessive gene for this vestigial wing and vice versa over here. And so Sturtevant, it's brilliant coming to this kind of idea, that if that crossing over of that occurs between the different genes, then we would have recombination, genetic recombination. But if it doesn't occur in that part of the chromosome there is going to be no recombination. And so where does that 17 percent come from? Well this is roughly 17 percent of that area of the chromosome. That's where it's coming from. If those genes were closer together that frequency of recombination would be closer. If they were really far apart, it's more likely that it is going to split in the middle. And so we can use this one cross to figure out the frequency of recombination. And then they were able to use that to build a gene map. And so if you look at a chromosome, if we look at that frequency of recombination, let's say it's 17 percent, that implies that it's an arbitrary distance of 17 map units apart on the chromosome. Let's say the frequency of recombination is less than that. That means the genes are closer together. What if the frequency of recombination is greater than that? It means that it's farther apart. What if it's exactly 50percent? Remember that's what we were thinking about. If it was independent assortment that would mean that those two genes are found on different chromosomes. And so we can use that to really map a chromosome. And so let's look at some of the data that they gathered. They found that the distance between the vestigial and that black coloration gene, the frequency of recombination is 17 percent. They then compared that to another gene called the cinnabar which has to do with eye coloration of the fruit fly and they got these frequencies of recombinations as well. And so when you're figuring out a gene map what I would encourage you to do is always start with the highest frequency of recombination. So I'm going to start with this one. And just choose to put them on that chromosome. We'll say 17 units apart. So we're going to put the vestigial and the black apart by 17. Now let's go to another one. So let's figure out where the cinnabars are. Well if we start with the vestigial gene we know it's going to be 8 map units apart from that. So I could say maybe it's going to be over here or I could say it's going to be over here. So we have these two different alternatives. And so which of those actually fits with that last frequency of recombination? Well if I put it way over here, then we're going to have a frequency of recombination between that and the black. We know it to be 9 percent. But it's going to be a way larger number than 9 percent. And so I can narrow it down to this is where our gene map fits. Now let me give you a problem of your own. So now I've given you these four genes and their frequency of recombination. I would encourage you to pause the video here and then you try to map out where each of those genes are found on the chromosome. I'll pause. And then let me show you what the right answer is. And so what I would do is again start with the largest frequency of recombination. I'm going to put B & C really far apart. So I'll put B on one side, C on the other. What's the total distance of the chromosome? Remember it's going to be 50 map units. And now I could work backwards. And so now let me figure out, so I've got B and C. Where is D going to be? Well I can't put D way out here because I don't have enough map units to do that. So I'm going to have to put it over here. And once I've got D, I've got to figure out where A is. So I could work backwards to that. Well I know that A can't be way out here on this side, so I know that A has to be somewhere over here. So that would be the relative map distance or the relative gene map based on frequency of recombination. And so Sturtevant and Morgan did that over years and they were able to map out where the genes are found on the chromosomes. Now we don't do it this way anymore. What do we do today? We simply sequence the DNA. Once we sequence the DNA we can figure out where the genes are. But the cool thing is that as we compare that you could go right here to the fly base I was looking up, the vestigial gene, we know exactly where it is. But that maps up perfectly with the work of Morgan and Sturtevant. And so that is genetic recombination. It allows us to create gene maps. And I hope that was helpful.