Thomas Hunt Morgan and fruit flies

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. Bovary and Sutton independently had proposed the chromosome theory, that the chromosomes were the location for where these inheritable factors that Mendel first talked about were actually 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. However, they really didn't have good cellular proof that chromosomes indeed were the location for these inheritable factors.

We don't really start to get that until we start looking at the work of Thomas Hunt Morgan. Now, in 1908, he decides to study fruit flies. So why does he want to study fruit flies? Have you 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; you don't always have a lot of resources to do your work.

They had short lives and they reproduced a lot, so you could very quickly get many, many offspring in many, many generations if you wanted to study how the different traits were passed on or not passed on. 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. 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, "Okay, now this is interesting. Let me take this white-eyed male and begin to cross it with other females."

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. 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.

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 y'all are thinking: "Wait, aren't they all brothers and sisters being crossed to each other?" Well, yeah, they're 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.

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—three red-eyed and one 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.

That's interesting because this was a mutant that just showed up after he did many, many, many, many generations of observations. What was even more interesting about this three to one ratio—and that three to one is something that popped up a lot in Mendelian genetics—but what was even more interesting was that he only observed the white eyes in the males in this F2 generation, in this second generation of the crosses right over there.

So you're thinking, "Well, why is that a big deal?" He was a pretty astute guy, and he says, "Well, look, if I'm only seeing it in the males..." It's not like he only got four offspring; he was in the ratio, he might have had hundreds of them. But it was in the ratio of two red-eyed females for every one red-eyed male and one white-eyed male. So across these hundreds of this generation, he only observed the white eyes on the males.

He said maybe this is in some way related to the chromosome that determines sex. 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."

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 sex-linked chromosome, in this case, the X chromosome. The way that you would specify the genotype of that white-eyed male is, on his X chromosome, he had the white variation, he had the white allele, the white variation of that gene.

Then, on his Y chromosome, he had no variation for that gene. So we assume that it's only contained on the X chromosome. You've probably heard of heterozygous or homozygous; well, this is a case where you have 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.

The red allele—the notation is W plus, W plus—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 the 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 first mutant discovered for this gene, is the first mutant allele that we do.

So we name it after that white; this is the white allele. These right here represent the red alleles. So these are the genotype of the red-eyed female.

When you cross that first generation, well, the white-eyed male can either produce sperm that have the X chromosome in it, which is going to contain the allele, or sperm that have the Y chromosome in it, which is not going to contain the allele. The red-eyed female, well, they produce eggs—either way, whichever of these X chromosomes they contribute, they're both going to have the wild type allele.

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. 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: they still have red eyes. But now they are heterozygous; they're heterozygotes. They are carrying the white allele.

Now, the male offspring right over here—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. 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 what the crosses that you see in that next generation. If you took these red-eyed females, that we already established, 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. They get an X from their dad, which has the wild type, the dominant red allele. 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 flies here where they got the 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. 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. It wasn't until a couple of years that he finally found that first mutant white-eyed male. It was in 1910 and 1911 that he publishes these discoveries in Nature.

The reason why this is a big deal is he says, "Look, my observations are completely consistent with this 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.

He would go on, and his students that he worked with would go on to study this for many, many, many years. 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 of Mendel and this theory of Bovary and Sutton that maybe chromosomes have something to do with these inheritable factors.

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.