Thomas Hunt Morgan and fruit flies

- [Voiceover] Where we left off in the last video we were in 1902, 1903, and Mendelian genetics had been rediscovered at the turn of the century and Boveri and Sutton, independently, had proposed the chromosome theory, that the chromosomes were the location for where these inheritable factors that Mendel first talked about, where they actually were located. But we talked about in that video that that was just a theory. This was based on some observations of meiosis and seeing how chromosomes behaved, and they seemed to behave in analogous ways to some of these inheritable factors but they really didn't have good cellular proof that chromosomes indeed were the location for these inheritable factors. And we don't really start to get that until we start looking at the work of Thomas Hunt Morgan. Now 1908, he decides to study fruit flies. So why does he wanna study fruit flies? If you've ever seen a fruit fly, they're very very very small. So you could actually put a ton of fruit flies in one jar. So, that's convenient. You oftentimes don't think about the practical logistics of science, but you could put a lot in one jar. They were actually cheap, and that's another practical concern of science, is you don't always have a lot of resources to do your work. And they had short lives, and they reproduced a lot so you could very quickly get many many offspring and many many generations if you wanted to study how the different traits were passed on or not passed on. And so he spent some time, he started this in 1908 working with the fruit flies. And he kept breeding them, in search for some type of a mutant trait. In general when you look at traits in a species, the wild type, let me write this down, the wild type is the one that's typically seen, while the mutant trait is something that seems unusual. And after two years he finally discovers a mutant trait in his fruit flies. He finds a white-eyed male. So this is the white-eyed male right over here. He says oh, okay, now this is interesting. Let me take this white-eyed male and begin to cross it with other, well, with the females. And you say well how does this actually occur? Well, what you do is you take a jar full of females and you put the white-eyed male in there and then the crossing happens. And what was interesting was the inheritance pattern that he saw for this white-eyed trait. Because you have the parent generation here, but then in the F1 generation all of the females were red-eyed and all of the males were red-eyed. And so just off of that first generation it wasn't clear that anything interesting was going on. But then, when he crossed these to each other, and I know what some of you all are thinking, wait, aren't they all brothers and sisters being crossed to each other? Ah, well, yeah, they were probably half brothers and sisters if they came from different mothers, but some of them could have been brothers and sisters, but yes, that's what people are talking about when they're crossing the F1 generation. But when they crossed these with each other, he saw a pretty interesting pattern. He saw a three to one ratio of red eyes to white eyes, so for every four fruit flies he would see, let me underline these, he would see three red-eyed and he would see one white-eyed. So the white-eyed, the white-eyed trait makes a reappearance, which in and of itself is interesting. It shows that this can be passed on genetically. And that's interesting because this was a mutant that just showed up after he did many many many many many generations of observations. But what was even more interesting about this three to one ratio, and that three to one was something that popped up a lot in Mendelian genetics, but what was even more interesting was that he only observed, he only observed the white eyes in the males in this F2 generation, in this second generation of the crosses right over there. And so you're thinking, well, why is that a big deal? Well, he was a pretty astute guy, and he says well look, if I'm only seeing it in the males, and it's not like he only got four offspring here in the ratio, he may have had hundreds of them, but it was in the ratio of two red-eyed females for every one red-eyed male, for every one white-eyed male. And so across these hundreds of, in this generation, he only observed the white eyes on the males. And he said, hm, maybe this is in some way related to the chromosome that determines sex. And so what he was able to do is say, well, let's just assume that it is. Let's assume that that trait, that mutant allele, that mutant variation of the gene for eye color, let's assume it's carried on the x chromosome. And so the genotype for that first mutant fly, that white-eyed male that he found, we could call it, and this is the notation that people typically use, because this is a gene that we're assuming sits on a, it's sex-linked, it sits on a sex chromosome, in this case the x chromosome, the way that you would specify the genotype of that white-eyed male is, well on his x chromosome, he had the white variation, he had the white allele, the white variation of that gene, and then on his y chromosome he had no variation for that gene. So we assume that it's only contained on the, only on the x chromosome. You've probably heard of heterozygous or homozygous, well this is a case where you're hemizygous, you only have a version of the allele on one of your two chromosomes, one of the two that you've gotten from each of your parents. So this would be the genotype right here of the white-eyed male. The genotype for the red-eyed female is specified by, so it's on the x chromosome, and the females have two x chromosomes, just like in the situation for humans, so on each of the x chromosomes, we assume that the females start off with the red allele, and the red allele, the notation is the w +, w +. And you might say, well why don't we just use the letter r? Well, we could have, but the general convention in genetics is to use to letter of the first mutant type discovered for that gene, and then to use this little plus type for the wild type. So the wild type is the red eyes, and then w, which is the mutant discovered for this gene, is the first mutant allele, that we do so we name it after that white, so this is the white, the white allele, and these right here, these represent the red alleles. So these are the genotype of the red-eyed female. And so, when you cross that first generation well, the white-eyed male, he can either, he'll either produce sperm that have the x chromosome in it, which is going to contain the allele, or sperm which have the y chromosome in it, which is not going to contain the allele, and the red-eyed female, well they produce eggs either way, either which of these x chromosomes they contribute, they're both going to have the wild type allele. And we can see how this crosses. You could get an x from both parents. If you get an x from both parents you're going to be female, because you're going to be xx, and each of these females, since you've got one wild type and one mutant type, and the wild type turns out to be dominant, they still show, their phenotype is still red eyes, they still have red eyes. But now they are heterozygotes, they are carrying the white allele. Now the male offspring right over here, well, in order to be male, they got the y chromosome from their dad, so they're not able to get that white allele, and they get the red, the wild type, from their mom. And you could see it here, and this is why all of the males in that first generation were red. They only got one copy of the allele from their wild type mother. But then what was interesting is the crosses that you see in that next generation. If you took these red-eyed females that we already established, that these are all going to be heterozygotes, and so you can see they have the red allele and they have the white allele. And you cross that with red-eyed males. You cross it with red-eyed males, what is going to happen? Well, the females in this generation, in order to be female you have to get an x from your mom and your dad, and so they get an x from their dad which has the wild type there, the dominant red allele, and so regardless of which one they got from their mom, they're still going to be red-eyed females. Some of them might be homozygotes, some of them might be heterozygotes. But now we see something interesting happening in the males. You could have heterozygote male, male flies here, where they got the x from, where they got the red x from their mom. Or you could get the hemizygous white-eyed males, where they got the white allele, the white x, from their mom. And this is the exact observation that Morgan made. So it was a very interesting thing that he was able to see. He started breeding these in 1908, he started breeding these flies in 1908. It wasn't until a couple of years that he finally found that first mutant white-eyed male and it was in 1910 and 1911 that he publishes these discoveries in Nature. And the reason why this is a big deal is he says, look, this is, my observations are completely consistent with this eye trait, this gene, being on the x chromosome. So he was able to show a direct linkage between, in this case, sex chromosomes and these heritable factors that Mendel first talked about. And he would go on and his students that he worked with would go on to study this for many many many many years and he actually ends up getting a nobel prize for this work. And this is a big deal, because he's finally able to draw pretty substantive connections between these heritable factors Mendel, this theory of Boveri and Sutton that maybe chromosomes have something to do with these inheritable factors, and he's showing that this is actually the case, these sex chromosomes seem to carry the trait, or in this particular case, the x sex chromosome seems to carry the gene for eye color in these fruit flies.