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.