(He says “choreography,” but I think he means “chorography,” but I’m not sure. Can someone check? Please edit and make paragraphs at will.) Good morning! Gall morning, yes. So I want to pick up where we were last time. We talked last time about Mendel’s elegant experimental design, and not just elegant, but very careful too, and having organisms that bred true, and a lot of work went into that. We talked about his observations and his really great choice to count. We talked about his ability to look at numbers that were apporoximate, and somehow intuit what was interesting about them. He had to take rough numbers and say, Hmm, I think this is a 3 to 1 ratio. Although that was an abstraction, but a very good one on his part, and it’s hard to know when to make those leaps and when you’re kidding yourself, but Mendal got a lot of data. I didn’t mention that he just worked on not just round and wrinkled, but he worked on seven different traits across pea plants. All seven showed these very consistant properties of going…There was a recessive and dominant phenotype, and the first generation, the dominant phenotype, by definition, was evident in full force, and in the second generation, we saw three to one segregation. He felt pretty good about that. He made other predictions based on this, and he was able to put together a very coherent story, and, as I also explained last time, it sunk like a stone, because it was an utterly abstract story, the idea that there were these particles of inheritance, factors of inheritance, you couldn’t put your finger on it, and people hate stuff you can’t put your finger on. They say it’s just the model. (2:05) Well, as I mentioned last time, the discovery of chromosomes in cells, really laid the foundation of the beginning of a rebirth of interest in Mendalism, and Mendal’s ideas. And the interesting part of that characterization of chromosomes was the chorography that we talked about last time. That normally in cells undergoing mitosis in normal mitotic division to make more and more cells. When you stain the cells and looked at them before they went into meiosis, you saw these X like structures. However many there were, they lined up along the midline of the cell. They appeared then to, sometimes you could see them even kind of attached to, something pulling them back, and they would pull back to make two cells, each of which had half of the X. Somebody asked last time, I drew four chromosomes, “Was that because cell’s have four chromosomes?” And the answer is No. It’s because I had room to draw four choromosomes in that cells, so this time I drew six choromosomes, to indicate that you can have different numbers of chromosomes. They are usually, but not always, an even number of chromosomes in higher organisms. (3:26) But, anyways, so I drew six this time, and what’s interesting was this meiosis. The generation of sperm and eggs. For example, in animals, they are the chromosomes lined up with different chorography, they lined up in pairs, and where you could see differences in the shapes of chromosomes. Like, maybe the little crossing point was lowered down, they would appear or the chromosomes were shorter in length. They would appear to find their own partner, the one that had the same basic shape, and they would line up in pairs, and then they would undergo a series of two divisions: A mitotic I division, and meiosis I, and a second division meiosis II. And in meiosis I, you would get one copy of each pair. Then it would undergo a second round of division that looked very much like mitosis, where these X structures would be split into two pieces. The notion then that the pairs would go to singletons and upon fertilization, singletons would come together and reconstitute a pair, really did fit Mendal. And thus was born, the chromosomal theory of inheritance. So (oops!) the chromosomal theory of inheritance. Are you overwhelmed by the chromosomal theory of inheritance? Have I’ve given you overwhelming evidence to believe it? No, how come? Student: “Oh, we heard so often before that it seems natural to us now.” It seems natural to you know, but the only evidence is that there’s something else that’s got pairs in cells right? What’s to say that some other thing that pairs up in cells actually is the carrier of genes? The chromosomal theory of inheritance is that Mendal’s abstract factors, genes, live on these chromosomes, are these chromosomes, or something like that, they’re carried by these chromosomes. And simply the fact that the chorography of chromosomes is the same as it is the chorography of Menal’s genes, that’s correlation, in fact that’s ex post facto correlation. I never had any predictions that these chromosomes would do it, I just saw that the chromosomes did it, and I said, Okay, you know, that could explain Mendal’s observation about genes. And there’s a world of difference between “That could explain,” “That is consistent with the data,” and “That presents a compelling case that this is true.” So there were some people who immediately bought into the idea of the chromosomal theory of inheritance, and there are other people who remain great skeptics about this, that these chromosomes were in themselves, quite irrelevant to inheritance. And indeed many people who, at this point they were in the 20th century, felt that this whole business of genes was still not such an overwhelming idea anyway, and trying to unite these two was going a bit far out. (6:30) So now I have to bring you back to some of the things that we left unresolved last time. Which is Mendel’s second law of inheritance because if we’re really going to start building a case that chromosomes really do carry genes, then we better get some serious consisteancy with much more complex aspects of the theory, or we better look for some contraidictions. So, you recall, and I mentioned, that Mendel’s studied seven different traits. Two of them, roundness and greeness, both dominant phenotypes underlain by these hypothetical genes. Big R, big R, big G, big G. (RRGG) And the recessive traits associated with these same genes, wrinkled and yellow, rrgg. When you make a first generation cross, what do you get? You get round and green phenotypically and genotypically, what are they? RrGg. Right? That would be the genotype, and these organisms would be heterozygous. In fact they’d be double heterozygous. To be heterozygous for the gene that controls shape, and heterozygous for the gene that controls pea color. Okay? Now supposed we do a cross, back to rrgg (meaning RrGg X rrgg), the parent that has the ressesive phenotype for both of these traits. We’re practicing our words here. Right? What will this parent, the second parent contribute in its gametes. What will the gametes from that parent be (the rrgg parent)? Little r, little g, they have to be little r, little g, because that’s all it’s got to offer. So, little r, little g, okay? What will this parent contribute (the parent RrGg)? Could give a big R, big G, could give a little r, little g. Could give, in principle, a Big R, little g, or a Big G, little r. In theory any of those are possible. And, what’s the ratio that Mendel reports? 1 to 1 to 1 to 1 (1:1:1:1), so equal. That’s right. 1:1:1:1. That’s the independent assortment of traits. That’s what he call’s this: Independent assortments of traits. That is to say, the inheritance of round and the inheritance of green are uncorrelated to each other. Right? Knowing which ones you got for roundness and which ones you got for greenness, they don’t convey any information about each other. So how could we explain this in terms oftheory in chromosomal theory of inheritance? Well, we could explain this in termstheory of the chromosomal theory of inheritance by saying, for example, that in this heterozygous parent here, Big R, little r, were carried onby chromosomes that paried up with each other. Homologous chromosomes. And Big G, little g, were carried on a different pair of homologous chromosomes, in that meiosis picture there. Okay? So, if that was the case, then when these chromosomes segregated to, in the first meiosis step, meiosis I, it might be the Big R and Big G on the left side, or it may be the Big R and little g on the left side, it might be the little r and Big G on one side, etc. Because these are different chromosomes and could’ve chosen to line up in different ways. That’s all cool. So Mendel’s law of independent disassortment (not sure if it’s this word, since it’s not in the dictionary) is consistant with the chromosomal theory. Except, we pointed out last time, and except, if Big R and Big G were on the same chromosome. Then we’d have some explaining to do. So maybe Mendel was just lucky, and Big R and Big G happened to be on different chromosomes. But what if he takes a third trait? Well, maybe the reason he got 1:1:1 for those traits was it was also on a different chromosome. And the four trait? I said he studied how many traits? Students: Seven. Instructor: Seven traits. If they all gave 1:1:1 assortment, they’d all have to be on different chromosomes. How many chromosomes do peas have? How many pairs of chromosomes do peas have? Student: Seven. Instructor: Seven. Very Interesting. He might have just gotten lucky. In fact he did. You know that. They are in different chromosomes. Though it makes you wonder where maybe it had an eighth trait that did something funny, and decided not to put it in his paper. I don’t know. It seems interesting. Like I said, there’s choice involved on what you want to report what point here. So, suppose we instead had Big R and Big G, little r, little g, happen to have been on the same chromosome. Then they would’ve been inherited from the common parent here, say from here into the FI. The FI would look like this. There are different chromosomes that would look like this, there are same chromosomes that would look like this. And now, lets make a little score card, what’s going to get passed on to the next generation. We’ve got the possibility that it could pass on, this one, could pass on. Oh, let’s keep score. RG could get passed on, rg could get passed on, Rg could be passed on, and rG could be passed on. And if they are on different chromosomes, we’d expect a quarter, a quarter, a quarter, and a quarter. But if their on the same chromosome, what do we expect? What will come out of this? Either you’d get this one, in which case you get both Big R and Big G, or you get this one in which case you get little r and little g, then it would be a half, a half, zero, zero. (13:27) Ooo, that’s very different. What is Mendel’s law independent of assortment you say? It favors this (1/4:1/4:1/4:1/4). But Mendel’s law independent of assortment can’t possibly be right if we see this (1/2:1/2:0:0). So Mendel didn’t observe this. But if we really believe this chromosomal theory, we’d expect to see it eventually. So who’s going to be right? Mendel, or chromosomal theory? You vote for both (to a student). How many vote of Mendel? How many vote for chromosomal theory? How many vote for both? How can you have both? They’d be contradictory. How many vote for neither? Hmm, okay, fine. So, we have a very different prediction. Notice that these (RG and rg) are the parental type of chromosomes. They’re the ones that went into the cross in the first place. Big R and Big G. These are the non-parental types of chromosomes (Rg and rG). They’re the combinations of Big R and Big G that didn’t match either of the parents the combinations. That’s a new combination. Well, it took a while before folks sorted this out. And it was eventually sorted out in fruit flies. And, it is of course, the case, that neither Mendel, nor this strict prediction from the chromosomal theory turns out to be correct. Mendel’s law of independent assortment does not hold for all portraits, but this very rigid model of two alternatives does not hold either. Let’s take a look at some real data. The data comes from Thomas Hunt Morgan, a developmental biologist that eventually became one of the great geneticists of the century. At Columbia, Columbia University studying fruit flies. And he studied fruit flies rather than peas. Can anybody reason why he studied fruit flies rather than peas? Sorry? Has four chromosomes instead of seven? Phaaaa. You know, four, seven. Anybody been to Columbia University? I mean, it’s, where’re you gonna plant peas? Right? I mean, it’s in Manhattan. Also, what else is wrong with studying peas? They take too long. How many generations of peas are you going to get in a year and a half? Not so many. Fruit flies? How long do they take? Couple weeks. You get a generation every couple weeks. If you actually want to write some papers. I mean, if you have a day job as a monk, you can do these pea things that take a long time. But for example, if you’re trying to get a tenured at Columbia, you might want to actually do something that you can get couple generations every month or something like that. So the fruit fly is much better, they also don’t, you know, take fields and things. And you can grow them in little vials, with some food at the bottom, some yeast on it, the medium at the bottom and a little cotton stopper at the top. And you know, it’s very convenient. You can grow zillions and zillions of fruit flies. So that’s why the fruit fly was chosen: easy, short generation time, etc, etc. And there were a lot of nature variations out there. Geneticists love to choose organisms that are just easy to work with, so you can do a lot of work. And fruit flies do have four chromosomes. So n=4, that is, four pairs of chromosomes. So we set up a cross. The F0 cross was between a normal fly, and the way we say “normal” is in genetics is “wild-type.” Okay? Wild-type. That is the type in the wild. It doesn’t actually mean that is the type in the wild. It means whatever type the geneticist has chosen for his or her reference strain, but it’s called “wild-type.” And he set up a cross between a wild-type fly, by a fly with two interesting properties: Its body was black, and its wings were in bad shape, and they were called “vestigial.” They’re, you know, these funny little wingy things that didn’t work, hadn’t grown out right, etc. So, instead of the normal fly body with we color, which is kind of a tan around its middle, it was black all around its middle, and its wings were very short. The hypothesis is that there were genes controlling, and in fact by demonstrating Mendelian inheritance, black was a single Mendelian trait, which was recessive to the normal body color. Vestigial was a single Mendndelian trait, which was recessive to the normal body shape. (18:28) And the genotype of wild type is homozygous normal, which I will write as plus over plus now (+/+). Geneticists actually prefer plus terms rather than Big Rs and little rs. Plus over plus (now it’s +/+,+/+), and we’ll take a female. And we’ll cross her to a male, who’s homozygousgeneous for the gene that controls the body color there (b/b), and this gene (vg/vg) controls wing shape. And we’ll look at the offspring. So, it makes FI. The FI has the genotype plus over back (+/b), plus over vestigial (+/vg), FI. Okay? So then, what he does, is he takes, say these males (FI), and he crosses them back to these flies here, that have the double recessive phenotype, doing what we call a test cross. That’s now the name, we’re beginning to use more of these names. A test cross is when you cross back to the homozygote for the recessive phenotype. And what he get’s out, same exact picture what I drew before. Getting used to nomenclature, and getting used to, you know, slightly different nomenclature. Here, he always got black vestigial, black vestigial, black vestigial, black vestigial, from the parent on the right. And here, he could get plus plus, he could get black vestigial, he could get black plus, or he could get plus vestigial (++/bv, bv/bv, b+/bv, +v/bv). And, as we said over there, the predictions would be that if these were on different chromosomes, he would get 25%, 25%, 25%, 25%. If they were on the same chromosomes, under a very simple theory of the chromosomal theory of inheritance, he woud get 50%, 50%, 0%, 0%. And in fact what did he get? 965, 944, 206, 185. What do you make of it? Which theory is confirmed? Neither? Well, maybe this is just this statistical fluctuation around the first line. You don’t think so? How come? Student: Way too wild. Instructor: Way too wild. But I mean they’re wild types so maybe… Yeah, so, you think those number are too far off a quarter, quarter, quarter to be believable? Student: Too much relation between ++ and bv. Instuctor: Ooo. Not only are they way off a quarter, quarter, quarter, quarter, but something is fishy. The two parental types are much higher than the two non-parental types. That’s saying something to you. Oh, interesting. What about this other one? 50%, 50%, 0%, 0%? Can this be a flunctuation around zero? No, this one’s pretty easy to reject, because zero, this is not like close to zero, this should be zero. You should'nt be able to see anything of those. That’s right. Because they wouldn’t go in if they were in the same chromosome. So, what are we going to do? We’re acting like Mendel. We’re seeing something funny in the data here. You even saw something that is a little just beyond weird, but it’s actually a little weird in some interesting direction. How many of them are the parental type? It’s 965+944. How many are the non-parental types? It’s 206+185. So, let’s figure out what’s the proportion of the frequency of non-parental types. Well, it’s 206+185 over 206+185+965+944, which is 17%. Okay, so It’s 17%. We now know what the answer is. When you take two traits, and you cross them and you cross them in this fashion, two recessive traits, do a test cross, the ration will neither be a quarter, quarter, quarter, quarter, or it’s not gonna be half, half, zero, zero. In fact, it will always be 17%. Why not? Oh, but Mendel looked at his data, and said three to one, it’s trying to say three to one, isn’t this trying to say 17%? Yeah, well, see that’s the thing. What’s to be made of this number? What does 17% mean? Now as you all know this is genetic recombination. Right? You know that these chromosomes are exchanging material. I can’t kid you about that. But, put yourself in the days of Thomas Hunt Morgan. Looking at these data, and trying to figure out what is this 17% trying to tell him. There were people around Columbia, and elsewhere saying, “Ooo, this 17% number says a lot about physiology. It’s a statement about developmental relationship of genes.”And they were trying to read all sorts of things into these numbers. Now, the first thing is, let’s test some more pairs of traits. How bout another pair? You do that, you get 17%? Nah, turns out to be 8%. You do it with another pair. Maybe you get 9% So, it’s not a constant. We can reject the idea that 17% is some constant, like eyear, one over pi, or something like that. But we looked at these numbers, and a lot of folks wanted to interpret these numbers as physiological numbers. Something about the biology of these traits. (24:31) So, we can give this thing a name. The frequency of non-parental types. We can call this the recombination rate, because we got new combinations. Right? This recombination rate might mean, and you know already, that, you’re thinking what it really means is… Somehow, we have black, black, plus, plus, and in the FI, we have, vestigial, vestigial, plus, plus, and that somehow, these two chromosomes have exchanged genetic material, so that the new chromosomes you get is like this. And you get a recombinant type. You get recombination between these two chrmosomes. And there’s a recombination rate. And the recombination rate is how often this kind of an exchange occurs. And what does the recombination rate depend on? The distance between those two genes. You know this because you’ve been told this since kindergarten. Right? It’s in all the high school textbooks and things like that, or whenever. They teach genetics earlier and earlier these days. And it’s on T.V. and stuff. But, that’s a nice idea that the recombination rate depends on the distance. And this rate, it might be 17% or it might be 1% or it 8% or may be who knows, depends on the distances or reflection of the distance. Buty golly, what’s the evidence for that? Aren’t we just making up a theory to explain the data here? We’re just trying to fix the chromosomal theory. The chromosomal theory wouldn’t predict these recombinant types. It would predicted we only get parental types out. So, if we do get non-parental types out, we say, well, chromosomes are promiscuous and will exchange parts. Because we don’t always get the same ratio, we have to make up the fact that somehow the ration is different because of something. Distance. We can’t observe distance. No way that Morgan was able to look at the chromosomes and see where the genes were. So basically, any number you want to give him, he’ll just say, “It’s the distance!” This is not overwhelming. Now, what’s even the evidence that chromosomes exchange material? Why do we think stuff like that even happens. Ah. Turns out, you can take fruit flies gametes, and other gametes, and look at them in the microscope. What you do is, to look at them closely, the chromosomes, during meiosis, you put a cover slip on them, you squish them down, add a little dye and you look. And it turns out, that really truly, when you look in the microscope, you can see stuff like that. Of chromosomes lying on top of each other like that. These are called chiasmata. Crosses. Chiasma, or the plural chiasmata. You can see it in the microscope. So, does that convincingly constructively demonstrate recombination occurs? Are you overwhelmed? Why not? Yeah, you put a bunch of chromosome down, you put a glass cover slip over them and you squish them. The fact that two things lie on top of each other…I mean, this is what it takes to do sciences. You have to be pretty hardnosed about not willingly taking evidence that supports your theory just because it supports your theory. Skepticism is pretty important here. So, you squish down the cover slip, and sometimes, not always, but sometimes, some chromosomes lie on other chromosomes. Big deal. So how are we actually going to get any convincing predictions? That’s what it took with Mendel. What convincing predictions can we make that this recombination phenomenon has something to do with the disposition of genes along chromosomes, and if so, might provide some support for the chromosomal theory of inheritance. Well, when you’re in a quandary, you got some new area, you got some messy data, you need new thinking. Where do you get new thinking from? You get new thinking from students, because old folks are thinking, in you know, whatever way they are thinking. So what you really need are young students to come along to the field and look at the data in some fresh way. (29:33) So, in this case, the hero was a UROP student at Columbia. They didn’t call it UROP but it as the same thing. It was a sophomore working in the lab of Thomas Hunt Morgan, when he came along and solved this problem very nicely. Well, partly because sophmores are not polluted by all sorts of prior thinking. So, the idea of genetic maps arises through the work of one named Alfred Sturtevant. Sturtevant was a sophomore at Columbia in 1911. And while an student undergraduate working in the lab of Thomas Hunt Morgan, he went home, he was working in the lab, and he took home a pile of data. And he said, “I gotta make sense out of all this data.”I don’t understand exactly what’s going on. Here’s some of the data he took home. Morgan’s lab set up crosses not just involving two traits, but three traits, simultaneously. They actually set up crosses involving three traits: black, what’s called cinnabar, which is an eye color, and vestigial. They looked at the FI, went crossing back to the triply homozygous fly here, and they counted the number of different recombinant types of different sorts. You can look at recombinant types looking black and vestigial. We already got those data. You can look at recombinant types between black and cinnabar. You can look at recombinant types between cinnabar and vestigial. Now, I’ve drawn this as if these thing live on a chromosomes and I know their order. You’ve got to remember, we don’t’ know that they live on a chromosomes, and Sturtevant certainly didn’t know their order. Okay? But I have to draw it for you so I’m drawing it for you, cause the notation he used was much to messy, and there would be no point learning it. So, he begins to look at the data from these different crosses. What he finds, is and when he looks only at black and vestigial, so he ignores what happens with cinnabar, what’s the recombination rate, the frequency with which he observes new types. Non-parental types. Well, they’ve already done the experiment in the lab and what’s the answer? 17%. Now, he then looks at black with cinnabar. So he just, you know, covers up the genotype of vestigial. There are four possibilities: black cinnabar, black plus, plus cinnabar, black cinnabar (I know, there are only 3. Is he missing plus plus?). He looks at the parental types, black cinnabar or plus plus. He looks at the non-parental types, the recombinant types, plus cinnabar, black plus. He counts up the number of non-parental types to the total number of flies, and he gets a recombination rate of 9%. Okay? So I’m gonna draw you this. He took out a piece of paper and he drew himself black, cinnabar, vestigial. He said, “I believe this has something to do with distance.” (32:59) This was 17%. The probability of a cross over occurring, of a recombination occurring between black and vestigial is 17%. And , the probability of a cross over occurring, the frequency of a cross over occurring between black and cinnabar was 9%. Got any prediction? Cinnabar vestigial should be about 8% give or take. But what if this picture’s wrong? What’s another picture that might be where cinnabar is? Oh yeah, there’s an alternative picture, isn’t there? The alternative picture is black, vestigial, cinnabar over here. At 9%, 17%, in which case, what’s the prediction for cinnabar vestigial? 26% give or take. Right? We’ve got to be a little rough about these things. Well, that’s not a single prediction, but it’s down to two alternatives. He’s either expecting about 8% or he’s either expecting about 26%. So, two alternative predictions. So, cinnabar vestigial, combination rate, 8%. Mmm, that’s good. That’s very good. That’s the first time anybody’s made a prediction. And a quantitative prediction that’s just gotten verified by data. Sturtevant also does one other interesting thing. He looks at a fourth thing, which is a little bit interesting. When I look at the types of gametes that can come out of here, right? If this idea of genetic recombination is correct, that sometimes, in this FI parent, a cross over has occurred here. Sometimes, a cross over has occurred here. And the cross over here would give rise to black plus plus, or plus cinnabar vestigial. Here it would give rise to black cinnabar plus, or plus plus vestigial. If it went the other way… Is it possible, that occasionally, under this model, you might get two cross overs. Might it be the case, if we believe in this stuff, that a cross over might occur between black and cinnabar, and a cross over might occur between vestigial and cinnabar. Could be. How often do you think that would happen? Sorry? Rarely. How rarely? What’s the chance of a cross over here? About, 9%, right? Cross over here? About 8%. Let’s say, 9%, 8% are about 10%, just for roundness. So it’s about a 10% chance of a cross over in the first interval, and a 10% chance cross over in the second interval. It’s about one percent of the time. Much lower than the others, but one percent of time you might see what kind of chromosomes emerging? Black plus vestigial. So, black plus vestigial, or plus cinnabar vestigial. These chromosomes, whoops, plus, thank you, (plus cinnabar vestigial is actually plus cinnabar plus) these would be doubly recombinant chromosomes, they need two recombination events to explain them. And you even have a prediction that you might see them at about 1%. And sure enough, Sturtevant sees them. It’s actually less than 1%. It turns out that double is a little less likely than the indepedant. There’s a little bit of what’s called interference, but don’t worry about it, that’s a second order affect. And at a frequency of about 1%, he sees double recombinant. That tells him who’s in the middle. If cinnabar is the one that has this property, because if he asks how often does cinnabar get inherited together with plus plus, that’s very rare. But vestigial gets inherited with plus plus, 9% of the time, black gets inherited with plus plus, sorry, 8%, and 9% of the time, but cinnabar’s pretty rare. (37:44) So, all this together says that this model here, of a linear chromosomes, is now making some pretty good quantitative predictions of what’s going on. But of course, this is just three different genes: black, cinnabar, and vestigial. What would you like? More, at least. All. I’d go for the all, I’m with you, but you know, he’s not a graduate, and he’s got what he can, so, more. And it turns out, of course, Morgan’s lab is busily making crosses and this kind of stuff, and there was more data available. So when they saw this happening, he said, “Alright, let’s look at some more things.” And began, because there was so much data from the lab, going around and taking all this stuff: low but curved wings, and other kinds of funny traits. And he began looking at frequencies and he found this was about 9%, and this was about 8%, and he found this was about 5%, and he found this was about 5%, and if these two were 5%, his prediction was 10%. And his prediction here would be 13%, and etc, etc, etc, etc etc, etc, etc. And it all pretty closely checked out. This was highly constraint, that the idea that the recombination rates would fit a simple linear model. It’s not perfect, of course, cause imagine what happens suppose I have 10%, 10%, 10%, 10%, 10%, I have ten “low sine” (this is the wrong word, but I don’t know the correct term), I have ten such intervals. What will the recombination rate be? 100%. And if I had 5 more? 150%? What does that mean? So, clearly, something is wrong about just using percents. You have to kind of, I mean, for the aficionados (not sure about this word either), really, the percent reflects the number of cross overs. But obviously you have to do a little bit of corrections because you can’t have, you know, if I keep piling on the intervals, double cross overs will happen and won’t produce recombinant types, you have to, but don’t worry about it. We’ll just add percentages for today. I mean, when you do all this it works. Sturtevant did this all in one evening. In his autobiography that he wrote about fifty years later, he says, “I went home one evening, blew off all of my homework, and stayed up all night, and was able to make sense of all these data.” So, I think this is an example of a productive all-nighter. And, also this is an example of when it’s the right choice to blow off your homework. If anyone wishes to do things like this and he’s productive, then you’re certainly entitled to blow off your homework here too. So, but do bring in good data like this when you’re done. (40:41) Anyway, this notion is a genetic map. A genetic map was a totally abstract concept, much like Mendel’s abstract concept, that there were even genes. Now we’re going farther, and saying whatever genes are, we still don’t know they’re DNA etc, etc. Whatever they are, they live on a line, and behave as if they live on a line. And they undergo recombination etc. And when I see a recombination rate, a recombination frequency, a recombination rate that’s zero, it must mean the genes are very close together. If I see a recombination rate, you know ,very very close, it’s never recombined, recombination rates, oh I don’t know, maybe 10% or something, well, there’s some distance between them. And if they get further and further and further away, or on totally different chromosomes, what would be the recombination rate here, for two different chromosomes? A half. Half of these are non-parental types. So when I get up to a recombination rate of 50%, then it means they live on, that they are so called unlinked to each other. Either they’re on different chromosomes, entirely, or I suppose it’s possible, and in fact it is possible, that they’re so far away on the same chromosomes, that the probability of cross overs occurring is so high, that they’re de-correlated from each other, and I can’t observe any recombination rate less than 50%. It turns out many chromosomes are sufficiently big that lots of cross overs can occur, and you can’t actually detect linkage at the two ends of the chromosome. But if you string together some genes in between, you can see that this is linked to this, this is linked to this, this is linked to this, is linked to this, is linked to this, okay? Alright. Good. So Sturtevant is another one of my heroes because he comes up with this utterly abstract model here, of chromosomes, of genetic maps. Oops, meant to get that board. Someone have a call? Okay. So, last of all, you take section four here. This begins to provide fairly convincing evidence for the chromosomal theory, cause it made a whole lot of pretty wacky predictions, and they pretty much hold up. Here’s another thing that provided a lot of good evidence for it. And that, was sex linkage. Also in Morgan’s lab, which was a very productive place, I might have to say. Folks were wondering about the fact that chromosomes, although they almost always occurred in pairs that lined up with each other perfectly. In many species, there was one odd couple. A pair of chromosomes that always paired up with each other, but they didn’t look the same. This one looks like an X. This one kind of has the shape of an Y. And hence they got the name of the X and the Y chromosomes. Now here was something very interesting. In fruit flies, it was always the males that had an X Y pair. In females, it was always an X X pair. What does that tell us about these chromosomes and what they do? Sorry? Determines gender! Wait a minute, why do you believe it determines gender? Just correlated with gender. Females have these two funny chromosomes, males have, sorry, females have these two Xs, males have an X and Y. Does it have to mean that they determine gender? Maybe gender determines them. Maybe what happens, is in female cells, you get both chromosomes, but in male cells, some enzyme comes along and chews off the end of the chromosome. No, no, no really! Maybe this is a some physiological state of the chromosomes. Why are you so ready to leap to the conclusion that the chromosomes determines sex, rather than the gender determines the chromosomes? Cause you know the answer, you’ve been told all this etc. But I again, ask invite you to take part in what support you have for that and ask, how would you know? Right? All of these things you get told, but, how do you know? And, there was great argument about what was really the case. So, how could you convince people that this was true? It’s not obvious to know which way it would go. The most convincing evidence, not the only evidence, but the most convincing evidence, came from a single fly that had been isolated in Morgan’s lab. And F0 fly that had a very interesting property, that instead of the normal red cephalo (not sure about this word, ditto) eyes, this fly had white eyes, where this, was the normal fly, with red eyes, and we’ll use a female. When we cross together the white eye fly and the red eye fly, what you find is in the F1 generation, all the flies, male and females, are normal red eyes. When I take, however, a normal female, and I cross her back, sorry, a normal female emerging from the F1 generation, and now I cross her to a normal male, here’s what happens. All of her daughters are normal, but her son’s, half are normal, and half are white eyed again. That’s weird. For the first time, we have a genetic trait, eye color, that is showing correlation in its inheritance with sex. (47:20) So that says, for the first time, we’re beginning to see something that looks like linkage. Like genetic correlation, genetic murals, like genetic mapping, that would relate eye color to sex. What’s the model? Of course the model here, is that this fly, we know the answer, is X over Y, it’s a male. And the X chromosome here has a mutation that makes it white-eyed. What’s this normal fly over here? X over X, and its X chromosomes are normal. When we go to the next generation, what kind of offspring are there. The daughters of this cross, what’s their genotype? What they’d get from dad? They always get a normal X chromosomes from dad, sorry, from mom, I mean. What do they get from dad? These daughters. They always got the X with white eye. Why didn’t they get the Y? Cause they’re daughters. Right? If they got the Y, they’d be sons, but they’re daughters. So, the daughters always are getting this chromosome. Now, when you mate these back to a normal male, X over Y, the daughters are of what type? What do they get form their dad? Always an X+. And what do they get from their mom? Either an X with a mutation or an X+. With Either way, they’re normal. Because we’re assuming this white eye mutation is recessive. What do the sons get? What do they get from their dad? A Y. Why don’t they get the X? Cause they’re sons. What do they get from their mom? Half of them get the X+, half of them gets the X mutant. And that explains, clearly, what’s going on. Now, the Y chromosome, being a short, stubby little chromosome, doesn’t have a copy of this gene for eye color at all. So you might as well regard it as being, you know, the allele for the recessive trait. It doesn’t have any functional copy. So the male, he only gets a copy from mom. And, what he got from mom completely determines his phenotype. Thus, the transmission of eye color, a trait controlled by the gene on the X chromosome, correlated so beautifully with the transmission of the trait, sex. That provided a convincing argument that that it was the chromosomes controlling sex rather than sex controlling the chromosomes. Alright, so you all know this stuff. You’ve all heard of Mendel, you’ve all heard of recombination. You’ve heard, I suppose, of genetic maps, you know about X and Y chromosomes and things like that. But I want you to take away from all of this, is that in order to really know things, you have to struggle against models. You have to know understand whether a model is just being made up to explain the data, or whether the model has been proved, by testing it, in serious kinds of ways. All this stuff took thirty or forty years of serious battle, before the last people caved in and said, this is all proven. Of course, going forward, we’ll assume this is all proven, and you know what to do with it, and onward to next time.
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Last Modified 5/22/07 4:20 AM
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