Hi. It's Mr. Andersen and today I'm going to talk about linked genes. When
I teach biology one of the hardest things to explain is linked genes. And so I'm going
to kind of go through this slow and make sure that I hit all the points. And hopefully you
can have the aha moment when you finally understand how linked genes work. Most of this is through
the work of Thomas Hunt Morgan. He bred fruit flies and kind of took the work of Mendel
and then pushed it into modern day. So this is the early 1900s. And so the people, Thomas
Hunt Morgan, the people who worked in his lab discovered so many things that we now
kind of take for granted. First of all these are fruit flies. Fruit flies are really hard
to see with an eye. You have to look at them under a dissecting microscope. But basically
you grow them in a medium like this. They'll lay eggs. You take the eggs out. They'll hatch
into larvae and then the next generation of flies shows up. And so this is what a fruit
fly looks like when you could zoom into it. You can actually, if you were to look really
closely, you would see that there are two types of fruit flies here. And they're separated
by gender. In other words, this one right here is going to be a male. It kind of has
a rounded rear end. And then it also has these things up here on it's arms. Those are called
sex combs. And the sex combs are a good way to tell the difference between the males,
so this would be a male right here. And then you could tell right here no sex combs. Kind
of a pointy end, so this is going to be a female right here. And so you could go through
and figure out which ones are male and female. But that's not what we're interested in. What
we're interested in is linked genes. And so in the fruit fly lab of Morgan's fruit fly
lab, basically whenever he found a mutation then he would breed that mutation until he
had a pure amount of that. And so you can see here that this is a fruit fly that's got
two mutation. First of all it's got a color that's black. And then it has these vestigial
wings. And so everything else is going to be the same between these two fruit flies
except the color and then the wings, vestigial wings. They can't fly because they have these
little nubbins of a wing. And so basically he was doing work on fruit flies and so the
nomenclature for genetics on fruit flies is pretty simple but it can be a little scary
if you have never seen it before. So basically we take a trait, in this case this bl bl is
going to stand for the black mutation. And then the vg vg stands for the vestigial wing
mutation. And so then you just take those letters and then you add a plus to it for
the wild. And so this would be wild type for both of those genes. Okay. So let's say we
were going to do a cross between these two. The way you would set it up, and again if
you're not sure on how to do this, make sure you watch the podcast on punnett squares.
But basically this one can either give the vestigial or the vestigial. Excuse me, the
wild or the wild. And this one can give the wild or the wild. So basically in meiosis
it's only going to be able to produce this one gamete right here. The female. The male
over here, since it has two of the mutant genes, it's only going to be able to produce
this gamete right here. And so if we were to do a cross between the two this would be
what we get. So we're going to have a hybrid for these two traits. So it's going to be
heterozygous, heterozygous. And so you might think to yourself what's that fly going to
look like? Well if these are recessive genes, then we would expect it to look like a wild
type. If these are dominant genes, we'd expect it to look like the mutant type. But if it's
a combination of the two, we might have one that's black with normal wings. So let's figure
that out. So I'm going to go to the fruit fly lab. So the fruit fly lab, this is at
science courseware.com/vcise. And so basically you can do any cross that you can imagine.
So I'm going to order those fruit flies. So I'm going to order the flies. Again the female
was of the wild type. So I'm going to add that to the cart. And now I'm going to figure
out the male. So the male again had a body color that's black and then it had a wing
size that was vestigial. So I built the male. I'm going to buy that. And I'm going to check
out. And they already arrived in the mail. So I'm going to throw this cross in the incubator.
Remember it's going to hold on to those ones that I ordered, and I'll come back to that
in just a second. So I'm going to throw it in the incubator. And so two weeks later we're
going to have that next generation. Alright. So now I'm going to pull those out and we're
going to . . . let's try that again. I'm going to pull those out. And we're going to up it
underneath the microscope so we can see what came from that. So throw that under the microscope.
I'm going to sort it, normally you apply like ether to the flies and then you can separate
them with a paintbrush so you don't kill them. They're just asleep because you're going to
use them again. So what I've got is two piles of flies. And so let me look at the female
right here. So the female right here is wild for color and wild for wings. And so we know
that those two mutations are recessive. Now what I'm going to do right now is add this
and use it in a new mating. So I'm going to add that. And we'll come back to that in just
a second. Let's make sure the males, so the males over here. Those are all the same thing.
So they're going to be wild as well. And so it looks like those two different traits were
recessive traits. So let's kind of go back to the keynote for a second. And so what did
we get for a fruit fly? We got wild type of those two. Okay. So that made sense to Thomas
Hunt Morgan. This was just Mendelian genetics. And so if he would have stopped there he wouldn't
have learned anything. So what I'm going to do is take this, the daughter in this trait
and let's cross that with a homozygous mutant for both types. Okay? So now we have a hybrid
over here. It's essentially a daughter from that cross and we're going to cross it with
the dad in that first cross. I know that's gross but that's basically what we're going
to do. Okay. So what could we get for gametes? Well this one again can only give the bl or
the black mutation and then the vestigial wings. But this one over here can actually
produce four different types of gametes. Because we could have the wild with vestigial. We
could have the wild with, wild with wild. We could have the wild with vestigial. We
could have the black with wild. And we could have the black with vestigial. So there are
essentially four different gametes that we could get for that. So let me lay those out
here. So we've got that. And if we were to do our punnett square these would be the four
types that we could get. And so in this cross, what would they look like? Well this right
here would be, it's going to be wild, wild. This one right here is going to be wild vestigial
wings. This one right here would be black wild. And this one would be black vestigial
wings. So this is what the fruit flies would look like. And so according to Mendelian genetics,
we would have a 4 by 1 punnett square. And so we would expect if we bred these that we
would have 25% of each of these four types. Now the reason I've shaded these ones in yellow
right here is that those are parental types. In other words they look like the parents.
So this one looks like the mom. This one over here would look like the dad. But this one
is going to be a combination of the two. This one is going to have that normal coloration
but vestigial wings. This one would be the black. So this is what they predicted would
happen in the cross. But what they found was way different than that. And it led to the
discovery of the linked genes. So let's go back to the lab again. So what I'm going to
cross now is, I'd already taken that female. So that heterozygous female from this cross.
So now what I'm going to do, I added her to this mating right here, but I'm going to add
the dad to that as well. So I'm going to add the dad to that mating. Yes. And I'm going
to let them mate. And so two weeks later we're going to take a look at the offspring that
come from that. Alright. Let me pull that out. Put those under the microscope. And so
you should be thinking, you know hypothesis testing, what should I find under here? Well,
we'll always assort them according to gender. And so we should get eight piles of flies
and they should be equal in size. So let me sort the flies and see if that's what we get.
And so this is weird. The results you get should freak you out a little bit. And they
freaked out Thomas Hunt Morgan as well. So let's click at what this is. Well this is
a normal wild. So let's zoom out again. So that was one parental type. This would be
the other parental type. So it looks like there's actually more of the parental type
then there are of the recombinant. So if I look at the recombinant, this would black
with normal wings. Or if I were to look down here and this is probably going to be normal
coloration but vestigial wings. And so if you look at the data, let's actually send
the data to the computer. And look at the results. And so I'm going to click this button
up here to ignore sex. Because there's no difference in the genders. In other words
if we look right here, there's a wild type male 264. Wild type female 273. There's no
difference between those. Doesn't look like it's sex linked. So I'm going to ignore the
sex. And so what do we find? Well we find that roughly we are getting 42% of the wild
type. We're getting 42% of the vestigial parental type. But we're only getting like 7.8% of
the 2 or about 8 percent of each of these two. And so when they got these results it
kind of freaked them out. In other words what they found is that they normally ended up
getting around 83% of the parental type, these two. And then they only got around 16-17%
of these other two. And so they thought there was a mistake. So they crossed it again and
again and again and again and again and they found the same thing. It just kept happening
over and over and over again. So let's go back to our flies. And so what we're getting
instead of the 1 to 1 to 1 to 1 ratio, we're getting this weird ratio where we have basically
of these two parental type, we're having like 83% of the parental type. And of these two
we're getting like 17%. And so they crossed it again and again and again. And they just
kept getting the same thing, over and over and over. If I remember right, they started
to think maybe there's something about 17%. Maybe they discovered the new pi, this new
irrational number. And they couldn't figure it out. Basically I love this story because
one of the students of Thomas Hunt Morgan, his name is Sturtevant, his last name is Sturtevant.
I think Reginald, I can't remember. Alfred, I'll have to look it up. But basically Dr.
Sturtevant, we'll call him, was up one night. He was a student. So 19 years old, something
like that. And he was trying to solve, what is it about this 15%, just thinking about
it. One night he just blew off his homework and worked on it all night. And then came
up with this solution. And the solution is that those genes are linked. What that means
is that they're on the same chromosome. Now they had discovered the work of Mendel. They'd
seen these things called chromosomes. They could see them under the microscope. But what
Sturtevant and Morgan did was they brought together these two concepts. The concepts
of Mendelian genetics and chromosomes and you came up with chromosomal genetics. And
so what does that mean? These two genes are on the same exact chromosome. And so that
means that they tend to go together through time, genetic time. Example in humans, freckles
and red hair are on the same chromosome. So they're going to tend to travel together.
Now this is the point where people tend to get it, "Oh, I get it now." And then they
leave it. And they don't really go deeper in linked genes and try to figure out, well
how does that all work out? And so when I was thinking about how to present this, the
best way to do it is to show you the chromosome. So we're going to go through the same exact
process that I had. But instead of just putting the terms down here, I'm going to actually
show you the chromosomes. Okay. And so how does this work? Well, this is that first cross.
This is going to be through the wild type and the double mutation black vestigial wings.
And so this is what the chromosome would look like. Now they are actually going to produce
four chromosomes, but since these are the only genes they have, you can only create
one type of chromosome. No matter how you organize it, you can only create one type
of chromosome. And remember in meiosis, let me bring up a color that I can actually draw
it in. Let's try black. There you go. So again, in meiosis you're going to produce a sister
chromatid to this. So it's going to look like that. We're going to have the two genes on
it. Remember there's going to be another homologous chromosome down here. This is an awful drawing.
So this is going to have the same exact genes. And there's going to be cross over between
these two. But since these are the only genes that you have, as you go through meiosis the
only gametes that you can produce are going to be gametes that look like that. That's
the only thing that we can produce. And so let me show you how that works on the punnett
square. Well these are the two chromosomes now that have the genes on it that are going
to come together. And those are going to create a new fly. And so that fly is going to be
a hybrid of the two types. So this should make sense. And it made sense also when they
did the crosses. But let's get now to the F1 cross. Okay. So if we look at this parent
right here, this parent right here is going to have gotten the wild genes. So that wild
chromosome, we could back up again. So it's getting this chromosome. This is the daughter
remember. It's getting that one and then it's getting this one. So if we look on the next
slide, so this would be the two chromosomes that we have. This one right here, no matter
how much mixing and crossing over and independent assortment we have, you just got these two
genes. So you can mix them up as much as you want, but you can really only produce this
one chromosome down here. But this one up here, it can produce, it can just hand this
chromosome off. And this would be one parent. It could hand this chromosome off. And it
would create another parental cross. So it could produce these two parental crosses.
But how could we ever create these recombinants? How could we ever do that? Well basically
the only way we could do that is if as it makes a copy of itself, and puts the chromosomes
overs here. So it would be a bl+ and a vg+. And this one is going to do the same down
here, like that. And again they're going to do crossing over. And this is the bl on this
side and the vg+. The only way we could create one of these new chromosomes is if it were
to crossover and we were to cut between, right here, between these two genes. And this one
were to swap down here and this one were to swap back over here. Or this one were to swap
here and this one was to swap back. In other words, if you look at a chromosome like this,
during that crossing over event, if you have two genes that are really far apart, crossing
over is fairly random. And so sometimes it might cut here. Sometimes it might cut here.
Sometimes it might cut here, cut here, cut here. It's just going to make all of these
cuts. But the closer the two genes are, the less likely that it's going to cut between
those two and create recombinant chromosomes. And so basically to build these recombinants
you have to have a crossing over that cuts the two in half. And so what does that mean?
Well the frequency of recombination right here was again 17%. And that 17% means that
the genes are relatively close together. What would it mean if our frequency of recombination
is 50%? Well 50% means that they're on different chromosomes. And so there's going to be what
Mendel produced, what Mendel thought. That you would have 50% parental and 50% recombinant.
And so if we ever get a frequency of recombination or frequency of these new recombinant fruit
flies that is less than 50%, that means that the genes are linked. And the less that number
is, that frequency of recombination, the lower it is, the closer those genes are going to
be. And so let's say it's 48% percent frequency of recombination. That means that the gene
is going to be right here and the gene is going to be way out here. But if the frequency
of recombination is really low, let's say it's like 2%. It's really really rare. That
means that the genes are really really close to each other. Now that frequency of recombination
doesn't tell us where the genes are, but you could do a number of crosses between other
genes that are linked, and that's what Sturtevant and Morgan did. And you can create what's
called a gene map. And that's kind of fun to figure out where the genes are located
on it using a bunch of different frequencies of recombination. And if you're a total nerd
you could go to the fruit fly lab, find linked genes and start doing that. Build a gene map
of your own. And so that's linked genes. I know that took awhile, but I think it's important
that you have a really good conceptual understanding of how that works. And so I hope that was
helpful.