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.


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