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So where we left off on Friday was we had chromosomes and we
had started to talk about genes and chromosomes, and
where we'd used examples from humans and went through just a
couple of definitions of things.
We have homologous pairs, so humans are diploid.
They have two copies of each chromosome.
So two homologous chromosomes.
Chromosomes that look like each other.
We'll come to kind of an exception today.
But then also remember that you've got sister chromatids,
and those are the two identical strands connected
together with the centromere.
We also talked about things being heterozygous and
homozygous.
And remember, when you talk about those in terms of
alleles, we said big A, big A. That would be
homozygous for something.
But you can start to attach those to chromosomes.
So if you think about these two homologous chromosomes,
you could have one allele on one of these chromosomes, big
A. You could have a second one on the other chromosome--
big A if it was homozygous, little a if it was
heterozygous.
And then walking these through two types of divisions--
mitosis, which is conservative, which you want
to keep all of the information from cell to cell.
So that's what's happening every time your cells are
dividing in your somatic body.
So what's really important there is you don't lose any
information.
When you make the germline, though, you have to get rid of
half the chromosomes.
You're only passing down one chromosome of each pair to
your offspring.
And so we talked about how that happens in meiosis
through this two stage process.
And the really key thing there in thinking about genes is
that even though we started, in this case, with something
that was heterozygous for a particular allele-- a big C
and a little c--
by the time you get down to something that's going to make
either *** or egg, a choice was made.
Either you get the big C or the little c,
and that can be random.
And that's how you get that random segregation.
All right, so a couple of things that just seem to make
sense, seem obvious.
We see that genes are inherited in very predictable
patterns, how they go from parents to offspring.
Chromosome number is very constant for each individual.
All of your cells have 46 chromosomes.
Your germline has half of that.
And it's constant for a species, and chromosomes are
segregated during cell division.
So given that, it seems pretty obvious that genes and
chromosomes correlate really well.
And so it's very attractive to imagine that these
chromosomes, these bodies that you can see in cells, are the
things that contain the genetic information.
But just because something seems obvious doesn't mean
that it's true.
For a long time, we thought that the sun
revolved around the Earth.
That turns out to not be true, as I think pretty much most
you know this by now.
And other, smaller things.
We used to think that disease was caused by bad air.
Well, OK, you can feel miserable with bad air, but
that's not the cause of disease.
So even though something seems obvious, we actually have to
go through experiments to show whether or not those
hypotheses are true.
So we'll go through some of these hypotheses that
chromosomes and genes are connected to one another.
And again, you might think, you know, why don't we just
look at them?
Why don't we just look at a gene and look at a chromosome
and see if it's on there?
But we don't have a microscope that lets you look at a gene.
So everything here we're connecting an inheritance
pattern or something we can only infer to
something that's physical.
And so this is something that comes up over and over again.
We're dealing with things that we can't actually see, and so
we have to imagine their existence through some other
experiments.
And that's what genetics is all about.
All right, so we're going to try to figure out whether
genes are connected to chromosomes.
And there's something that was very key to this, and that was
thinking about what kind of chromosomes we have.
OK, so everyone in this room, you've got some autosomes.
I'll go through the definitions of those.
But some people in this room have a slightly different
chromosome set than other people in this room.
And the major difference is that between males and females
in mammals, we have X and Y chromosomes.
So these are chromosomes from a manatee, just because I got
bored of humans.
And what you can see there is that there's nice pairs of
everything.
This is from a female and from a male.
But when you look at one of these chromosomes, the X
chromosome, you have two nice large X
chromosomes in the female.
And in the male, you have this little piddly Y chromosome.
I'm going to just go back and forth through here.
So you can see that a little bit clearer.
X chromosomes look very similar to one another, and
this Y chromosome is much smaller.
So we're going to end up talking a
lot about fruit flies.
Fruit flies also have chromosomes.
I've actually shown you a couple pictures, and I'll show
you them again.
Fruit flies have fewer chromosomes, so it's actually
a lot easier to see their sex chromosomes.
So we're going to talk a lot about experiments that were
done by Thomas Hunt Morgan and his group of students, and how
they used chromosomes from the fruit fly to figure out sex
linkage and also some other important things.
So what you can see if you look at the male or female
chromosomes-- just sort of diagrammed here--
remember, these only have four pairs of chromosomes.
But if you look at the sex chromosomes in the female, you
see a pair of chromosomes that look similar to one another.
So the X and the X. Frustratingly, the X
chromosomes don't actually look like Xs.
They look like Vs.
But if you look at the male, he's got one of these.
But he also has another chromosome that kind of is an
X shape, but is actually the Y chromosome.
So that's what we're going to be spending our time on.
I'm going to give you a couple of definitions to follow these
types of chromosomes.
And they're pretty straightforward, particularly
if you're a fan of classic languages.
But heteromorphic chromosomes.
So, "hetero," different. "morphic," shape.
This is like the X and the Y. They're different shaped
chromosomes, but we call them homologs.
So last time I said homologous chromosomes are the ones that
look like each other, and they pair up during meiosis.
So the first part of that statement isn't exactly true.
The second part, that the two chromosomes pair up--
they pair up during prophase, and they stay on the metaphase
plate in meiosis together--
that's the really key thing.
These homologous pairs of chromosomes are the ones that
will interact physically with one another through meiosis,
and I'll walk you through how that happens.
Sex chromosomes are associated with male and female.
Not all organisms have them.
Mendel's pea plants, for example.
Peas don't have X and Y chromosomes.
They don't have sex chromosomes.
So they do sex differently.
They're also both male and female, so you can imagine
they would have to do it differently.
But sex chromosomes is sort of the shorthand that we're going
to be doing to talk about X and Y. In mammals, anyway, we
have X chromosomes and Y chromosomes, and the
males are the XY.
In chickens, they also have heteromorphic chromosomes.
They're different shapes, but the females have the two that
are different, and the males have the ones
that are the same.
So it doesn't always correlate.
We're going to stick mostly with mammals
and with fruit flies.
So if there's a name for these special sex chromosomes,
there's a name for all the other
chromosomes, and that's autosomes.
So that's just everything else that's not a sex chromosome.
So in fruit flies, like us, females are XX
and males are XY.
You'll find out a couple different things between them
and us, other than the fact that they're
flies and not people.
But in general, those are the important
things for the moment.
So I said that these are homologous chromosomes.
And so if we watch them through meiosis, they'll have
a very particular behavior.
So if we look in meiosis I, and we look at metaphase,
these guys will line up.
So if you have autosomes--
so let's look at a male, for example.
We're going to use these to be the autosomes--
a pair of two--
and then those will be the sex chromosomes.
So in meiosis I and metaphase, the homologous
chromosomes line up.
So those two autosomes will be next to each other, and the
sex chromosomes will also be right next to each other.
And so when those separate in anaphase I, what you get are
each cell has an autosome, but any cell has a sex chromosome.
But they have different sex chromosomes.
So you have this chromosome going to one daughter, this
one going to the other.
And so when you talk about having female and male ***,
in a way, that's because already at this division,
we're having something that's going to only give this type
of sex chromosome, and one that's going to give this type
of sex chromosome.
All right, so if we then follow one of these--
so we're just going to follow this guy now
through meiosis II.
And metaphase is going to do exactly the same thing as all
the other chromosomes.
The autosomes will be in the middle, the sex chromosome
will be in the middle, and then when you separate those,
you'll get the two halves.
So in this case, coming from this one, it's going to make
two of the same ***, basically.
And from this one, it's going to be making two of
the other sex ***.
Questions so far on sex chromosomes?
All right.
OK, so because these are sex chromosomes, and being female
or female seems to be correlated with them, you can
start to make some predictions.
And this is true of inheritance where you can say,
you know, if I think about a male and a female, and males
are XY and females are XX, then you could trace where any
individual has to get their X or their Y chromosome from.
So females, for example, their X chromosome--
they have two.
One comes from mom, one comes from dad.
Males have an X chromosome.
They also have a Y chromosome.
The Y chromosome they got from dad.
So their X chromosome they have to get from their mom.
And Y chromosomes go from father to son, because that's
the way that we can tell something is male.
It has a Y chromosome.
And so you can start to--
we'll just take the X chromosomes.
Let's do a cross of the male by female.
And if we call these X chromosomes maternal and this
one paternal, just to keep track of who they came from,
then whenever we have someone who's XX, because the
chromosomes and genes sort independently, you get a
maternal and a paternal.
And anytime you have an X and a Y, you get a maternal.
So this would be the prediction, and so this is
what we're actually going to follow through to see how
certain things behaved, and to nail down that genes actually
were associated with chromosomes.
Again, when you have 46 chromosomes of a human, and
you want to say that genes are connected to those,
it's kind of hard.
But if you say the sex chromosome
does something different.
It behaves different genetically, and I can follow
that one physically, then it's a little bit easier to make
that correlation.
And when you've got fruit flies where you can smash the
cells and look at the chromosomes, it
makes it even easier.
So we'll talk about some fruit flies now.
So Thomas Hunt Morgan was a fruit fly geneticist in New
York City, and he decided to use fruit flies, probably
because in New York City, it was a lot easier to find fruit
flies and other flies than it was to find pea plants.
They're similar to pea plants.
They have lots of different traits.
They reproduce rapidly.
They don't self themselves.
You have to cross them to one another.
But they certainly do it quickly.
And there were a few other things that made these nicer
to work with than pea plants.
So what are those things?
One, they're very small.
You could easily study thousands of them in the lab.
And the other thing is that male and female were separate,
and they had sex chromosomes.
Pea plants didn't have either one of those things, so to
follow anything having to do with sex or sex chromosomes
was a lot harder to do.
In fact, impossible to do in a pea plant.
All right, so we're going to need to start off with what do
you know about fruit flies?
So fruit flies, these beautiful little specimens
here, turn out to actually be really fundamental to a lot of
biology that we do now.
And there's a lot of people at Stanford that use fruit flies
in their lab to do certain aspects of their studies, and
mice or humans for other parts.
So we test out a lot of things in fruit flies.
But you can see a couple of things pretty obviously.
One thing is their eye, which is huge.
It's a big compound eye.
And normal flies, the ones that you find floating around
in your bananas, have red eyes.
But Morgan discovered one day something that was white eyed.
And this was a little bit like that yellow mouse I told you
about at the beginning of class, where it literally was
he was looking around at his normal fruit flies and
something pops up spontaneously.
He sees this white eyed fly.
So of course, he ran around trying to catch it and see
what he could do with it.
It was a male, and so he immediately tried to mate it
to some females to see if he could then keep this white
trait in the progeny.
So there are a couple of terms that we need to
go through for this.
And first just has to do with wild type and mutant.
So wild type really is what you find in the wild.
It's the most common thing that we see out there.
It's the predominant allele.
It's the predominant trait.
And a mutant is something different.
Mutant doesn't mean bad.
It doesn't mean it doesn't work.
It just means different.
So that's the really strict definition of it.
Wild type is what you see when you go outside and
see most of the time.
Mutant is something that varies from that.
And a couple things to note about this.
The wild type allele, although it's predominant, it's the
most common, genetically, it's not always dominant.
And one example that you already saw was that yellow
mouse-- that agouti with a Y. That was a dominant mutation
that made the mouse yellow, but the wild
type mouse was brown.
So the most typical one was brown.
And as we get more into things like human genetics, we talk
about this less and less.
We don't talk so much about wild type and mutant, because
we recognize that if you look around, we have so many
different variants of anything.
Of hair color, eye color, height, that it doesn't really
make sense to talk about the dominant wild type allele and
this other mutant allele.
It will come up when we talk about a couple of diseases,
and I'll bring that up then.
But in fruit flies, we definitely talk about mutants
and wild types.
The other thing is to say that a phenotype also depends on
the population that you look at.
So if you were to go outside and look in the springtime,
all those California poppies that are all orange--
so that's a wild type for a California poppy.
Occasionally, you see a white one.
That's actually a mutant.
If you were in Iceland and you looked at Icelandic poppies,
those big red poppies, those are dark red.
And occasionally, you'll get a mutant that turns it orange.
So orange isn't necessarily wild type or mutant.
It's in relationship to the rest of the population.
All right, so we're going to go through a
couple of gene symbols.
These white eyed flies--
we're going to call them w for white or w minus.
So the mutant is often referred to with a minus, and
the wild type has got a plus sign.
Or sometimes, if we're pretty lazy, which you'll see me
getting pretty soon, we'll just put a plus there.
And the formal way that we designate all these alleles is
that the mutant is always named for the phenotype--
what it looks like.
So white refers to the mutant phenotype.
It's not that the gene makes white.
It's when you don't have the gene, you end
up with being white.
So that's going to come up a little bit later of how we
name these things.
But I just wanted to give you an idea of the different kinds
of mutants that are out there, giving you some introduction
to some of the different types of model organisms that we use
to figure out genetics.
So in fruit flies, you've got their heads with those big
eyes again, and their antennas,
and their mouth parts.
And different mutants that have been found over the years
can be pretty dramatic.
So this one is something called antennapedia.
Again, you guys know classic languages, you
can figure that out.
But so those are antennas.
Those are legs.
So antennapedia mutants, instead of having nice little
antenna, produce giant legs in front of their head.
So that's pretty dramatic.
There are actually people that study that.
But that's one of the examples of a mutant.
So normally, they don't have legs growing
out of their faces.
But they do in the mutant case.
So another example of something
that's used really commonly--
and for example, Professor Kang Shen, who's in the
biology department, studies neurobiology.
And he does this in a really simple
system called C. elegans.
It's a little worm.
And these little worms go along happily.
You can see there are little trails that they make.
And if my movie runs--
let's see if it does.
Of course it doesn't.
Yeah, I never practice things beforehand.
You can go look this up.
So if you could see the movie, you'd see this nice--
I'll have to interpretive dance.
So if you see the movie, it nicely goes like this, little
sinusoidal wave.
I can't believe I'm doing this.
So anyway, worms move nicely like this.
Uncoordinated worms--
this is going to be incredibly embarrassing
and caught on tape.
Maybe the movie works.
No.
Oh, it does!
I'm saved!
Uncoordinated worms don't really do that.
So they try, but they twitch and they don't
do this nice wave.
And you can actually learn a lot about that, because if you
imagine if you're interested in neurobiology, you want to
know how the nerves control muscles.
And so you look for these uncoordinated mutants and try
to figure out what's the gene that's responsible for this.
So those are some examples from the animal world.
In the plant world, this is actually
something that we study.
If you look at a plant, on the surface of it, it has these
little pores.
These pores can open and close, and that takes carbon
dioxide from the atmosphere into the plant and
then water comes out.
So plants can breathe in carbon dioxide.
That's great for us.
They spit out oxygen.
Also great for us.
And they're driving the global climate.
But these guys are called stomata.
And that's Greek for mouth.
So that's just the term.
And one of the unfortunate things about geneticists who
don't have much of a social life is that they start to
kind of come up with cutesy names for things related to
different phenotypes.
So even though this has to do with mouths, all of a sudden,
people started naming things too many mouths.
Or I'll show you an example.
This is a mutant that one of the TAs from BIO41 works on.
And it doesn't make any of those.
And that one's called Speechless.
There's one called Mute, which also has the same problem.
And then sometimes we have names that we kind of regret
afterwards.
So this is another former BIO41 student and TA, and she
was working on something, and she said, oh, it looks just
like challah.
And now we have to convince people why we have a plant
gene named challah.
So they're based on what the mutant phenotype is.
It's a cool gene, actually.
Maybe I'll tell you more about what it actually does later.
It does not make challah.
OK, so now you have some idea about how we name things and
the fact that the mutant phenotype doesn't tell you
anything about what the gene does.
It just describes what the mutant looks like.
So we're going to go back to what Morgan did with this very
precious white eyed male fly and see what happened when you
started to cross it.
So he crosses it to the wild type females that are in the
lab, and he looks at the F1s, and they're all red.
Red eyed, but red, because I don't feel like writing eye.
So is the white mutant dominant or recessive?
Yeah, it's recessive, because we see the red
from the wild type.
So now he crosses red females to red males from the F1s, and
gets an F2, and he gets a 3 to 1 ratio of red to white.
That all sounds good.
You've heard that before.
Dominant alleles, you're going to see a 3 to 1 phenotypic
relationship.
The one weird thing was that all the white
eyed flies were male.
So that ratio seemed to work out, but if you actually
looked at who was female and who was male, the females were
all red, and the males were all white.
So he had to think about that for a little bit.
Ah.
Yeah.
Does that say that you're crossing a male to a male?
It says that I'm crossing a female to a female, which is
equally wrong.
Thank you for catching that.
Any other things that I've said wrong?
So if you look at this and you say, nah, something is going
kind of strange here.
So he was concluding a couple things.
One is that eye color correlates with sex.
In this cross that he did.
It doesn't always correlate with sex, but in this
particular cross.
And so he had an idea that perhaps the white gene was
connected to a chromosome that's also connected to sex.
So either the X chromosome or the Y chromosome.
So he decides to do some more crosses and figure out whether
or not this is correct.
So we're going to start off looking at what he did.
So I'm going to show you how we're
going to do these alleles.
So to make sure that you remember that something is on
the X chromosome or on the Y chromosome, you write out X's
and Y's and then superscript the gene.
So first, we have to figure out if he thinks that this
white allele is connected to a sex chromosome, we have to
figure out whether it's on the X or the Y. So think about
that for a moment.
Any experiment that he's done that's let you know whether
it's on an X or a Y?
Anyone want to volunteer?
[INAUDIBLE].
So keywords there.
He knows it's recessive, and he showed that through what
experiment?
[INAUDIBLE].
Right.
So very good point.
So if something's on the Y chromosome, how could it ever
be recessive?
It doesn't have another chromosome with it.
But if it's on the X chromosome, then that first
cross that he did, we'd hide it essentially under the other
X. So perfect.
So he's going to say that there's a white that's going
to be on the X, and so when we have our wild fly, we're going
to call those w flies for female.
So then just a little Punnett square here, and looking at
what the male and the female are going to produce in terms
of their gametes.
This is just what you've done before, so from here, we have
from the father, the white allele, from the mother, the
white plus, or the red allele.
So we get something that looks like this.
And so when we look at what kind of alleles we have--
so we have the red allele all the time, and
red allele's dominant.
And so the results are 100% red.
And that's whether they're male or female.
Everyone was red.
So he's now going to say, I'm going to look at this again.
That will be coming down towards me.
[SIDE CONVERSATION]
It's on the top.
[INAUDIBLE].
Oh, all right.
Yeah, it does.
We're gonna continue on the other one.
OK, so what we have is that he's done his cross.
He's got him some progeny, and he's going to start to cross
the progeny to one another.
So he's going to take a male, and he doesn't really have any
choice, because all the male are the same phenotype and all
the female are the same phenotype.
So he's going to cross one of these by one
of the other ones.
OK, try that one again.
You got me?
OK.
It's weird, the spotlight and the camera.
I'm also trying to talk more like this rather than having
my back to you all the time, because I looked at those
images, and it's not so good.
OK, vanity.
All right, so we're going to do these crosses.
So these are basically the F1s from that last slide.
The heterozygous female by the male.
Now, I'm going to bring this up again, but we can talk
about something being heterozygous when they have
the two different alleles--
one on each chromosome.
But when we have a male like this, it's not really
heterozygous or homozygous, right?
Because he's got this other chromosome.
So we call it hemizygous.
I'll bring that up again.
All right.
So he's going to do these crosses, and follow the same
thing that we saw before.
OK, do you get any white flies?
Male or female?
Male.
Yeah.
So these guys.
So the only ones.
So it's basically that first cross that
I walked you through.
So he's gotten these.
So again, he's got white eyed males.
So he started off with a white eyed male.
He did some crosses.
He got some red eyed males again.
He's got another white eyed male, or lots of them from
this cross.
At this point, he might be worried.
Is it possible to get a white eyed female?
Every time so far, he's been getting white eyed males.
So what should he do if he wants to figure out if he can
get a white-eyed female?
Yes.
So which ones?
The bottom ones.
These two.
OK, perfect.
So let's see whether or not he gets anything white eyed out
of this, because essentially, we've got this recessive male,
and we're going to be crossing it to something that we hope
is this one.
So how do we know, actually, that we're crossing it to this
and not to this?
They're all just red eyed.
How do we know?
You cross it a lot.
Excellent.
Yeah, you cross it a lot of times.
So you cross a lot of white males to a lot of red females,
and you keep each one of them separately.
So nice little fly house over here segregated from the nice
little fly house over here.
And then you follow them.
Some of the times, you will have crossed it to this one,
where we expect everything to be red.
But if this works the way we think it does, then some of
them should be producing some white eyed females.
So let's just follow that through.
So we're going to cross something that is heterozygous
female and this white eyed male, and then ask whether or
not we should get-- what we are hoping to get is
essentially--
I'm only going to fill out one of these.
What we're hoping for is that we end up getting this one.
And in fact, that's exactly what he got.
So it's good.
So you can get a white female.
OK, so then remember there was this idea about who passes
genes down to which, from mothers to sons
and fathers to daughters.
So now we're going to do another cross to see whether
or not that's happening.
So if the idea is that the male always has an X from its
mother, then the males from this cross--
what color should their eyes be?
White.
They should all be white if that's true.
And what about the females?
They'd be the same.
They'd all be red.
Yeah.
Yeah.
So the females should be all red like their father, because
no matter what they get from their mother, they have to get
an X from their father.
So if this works--
so if we understand heredity correctly, then the prediction
is that all the males are going to be white, and all the
females are going to be red.
So does that experiment, and you can probably guess the
answer, since I'm telling it to you in class.
And that's exactly what he got.
So it all kind of works that way.
OK, so I just want to give you one other cross.
It's actually the cross that we did already that was
suggested by the front row here that in order to try to
figure out if we could get a white eyed fly, we cross the
one that was heterozygous for white to the one that was
homozygous for white.
And I just want you to look at this and realize that this is
actually a test cross.
We talked about those test crosses before where we have
something that's showing the dominant phenotype, red eye,
and we want to know what alleles it has.
So we cross it to something that's homozygous recessive or
hemizygous recessive.
So you can walk through that again, if you wanted to.
But we already covered that cross.
So a major conclusion was there's a nice, nice, nice
correlation between the chromosome and the behavior,
looking specifically at the sex chromosomes, and a
particular allele, that white allele.
So that's nice.
Seems to fit.
But Morgan was a little concerned.
There's only eight chromosomes and flies, and if you do the
statistics, it's possible that by chance you could get the
results that he got.
A very small chance, but still.
So he said, what I really want to do is find some situation
in which an incredibly rare event correlates with how a
gene behaves.
And if I have a prediction and that incredibly rare event
always works out to explain what my gene is doing, then I
feel like I'm on pretty solid ground.
So what he's going to do is look at some flies that did
something weird.
They actually screwed up somewhere in meiosis.
And so this is actually using something that, in some ways,
ends up being a terrible birth defect, and turning it into a
way of understanding genetics.
So before we get into this, any questions so far on sex
linkage in the normal way?
OK.
So when he has these red eyed males and white eyed females,
the cross that we just did where we say the sons are all
going to look like the mother, the daughters are all going to
look like the father.
Once in a while-- like 1 in 1,000 times--
that was not true.
So 1 in 1,000 times, the males were red or the
females were white.
Really, really, really infrequently.
So I showed you this picture before.
These are the chromosomes of fruit flies.
And they're big enough and a normal enough shape that you
could smash those cells and look at them.
And one of his students said, you know, once in a while--
like 1 in 1,000 times--
I see something weird in these slides.
I see that the number doesn't really add up.
And he said, OK, well, we have this 1 in 1,000 time that I
get the wrong color, and a 1 in 1,000 time that I get the
wrong chromosome.
Maybe this is the thing we're looking for.
The very rare event that we can correlate
with how a gene behaves.
So this is the hypothesis for what's going on.
So how do you get those flies that have the
wrong colored eyes?
And this comes back to meiosis.
Remember, meiosis is really important to get all those
chromosomes to line up in the center and then come apart
where one homologue goes to one daughter and the other
homolog goes to the other daughter cell.
But what if that doesn't happen normally?
So if we're in meiosis 1, so we draw a little metaphase
spindle, what we should have is that chromosomes
are all lined up.
And in a normal situation, we should end up, if you look at
those daughter cells, that each one of those gets one of
the homologs.
So that's the normal situation.
But what if you have something abnormal?
So they get one of their autosomes OK, but this one
gets two chromosomes and the other one gets none?
So what if that happens?
And just to draw that a little bit nicer, this is exactly
what I just showed you before, but someone complained,
reasonably so, a few years ago that they couldn't see my
writing very well.
So I color coded it.
So essentially, this is saying, look.
In meiosis I, if you look at all of the chromosomes in a
fruit fly, you have these that are autosomes, and this is the
X chromosome.
So this is going to be a female here.
So normally, they're all going to line up.
But once in a while, they don't go correctly to the
daughter cell.
So two of them go to one and none go to the other.
And one thing that's important to notice here-- so this is
called nondisjunction.
So disjunction--
remember, when they're together, they're joined, so
it's a junction.
Disjunction is coming apart.
So nondisjunction is like a double negative.
Nondisjunction is failure to come apart.
And what's important here is that this happened to one
chromosome, but it doesn't mean it's happening to all of
the chromosomes.
I mean, it is possible that all the chromosomes have a
problem, but more often, just one of them has this problem.
OK, so he's noticing this, and he says, here's my prediction.
Those really rare flies--
I'm going to be able to tell you what those alleles look
like by following what the chromosomes are doing.
So normally--
so this is not the disjoined fly.
This is the normal one.
So if I cross this white eyed female to the red eyed male,
what I should get are all the red females, because they all
get an X from their father.
So these ones.
And then all the males with their Y chromosome, they got
their X from their mother, so they should be all white.
But what if that X chromosome doesn't go equally to both
daughter cells, and just goes to one?
So our male here is going to be normal.
It's going to either contribute the X or the Y
chromosome.
But the female is not.
She's either going to give both of h er X
chromosomes or nothing.
So this is going to look a little bit weird.
So this is what we predict would happen.
So you've got two flies that have some extra X chromosomes,
one that just has one X chromosome, one that just has
one Y chromosome.
So the question is, does this solve this problem?
So again, w plus is going to be dominant.
So what we'd expect here is this is going to be red.
This one doesn't have any plus alleles, so this one's going
to be white.
This one's also going to be red.
And this one, we have no idea what it's going to be, because
there's no gene on there.
So one idea is that maybe those wrong things--
those white eyed females--
could be something like this, and those red eyed males could
be something like this.
But we don't know what this is.
So because you could smash those chromosomes and look at
them, it became pretty clear that this never happened.
You'd never see it.
So without an X chromosome, a fly can't live.
Turns out it can live perfectly fine without a Y
chromosome, which is obvious, because there's females
around, right?
They've never had a Y chromosome.
But not having an X chromosome is not so good for life.
So now he's got these other chromosomes, and he has to
figure out which one's which.
So it turns out--
do you think that one's female or male?
Female.
Yeah.
So this is actually female.
Even though it has a Y chromosome, it has two Xs.
And in flies, it turns out that having two X chromosomes
makes you female, even if you have a Y chromosome.
So again--
I think you put the man sign up.
Sorry?
You have the man sign up.
Sorry.
I'm not very good with this today.
No, I erased you.
Away.
OK, so then the male is going to be--
and I did correctly do that symbol.
So learned a couple of things.
One, those really exceptional events correlated with
chromosomes and alleles.
And then we also learned that sex determination is a little
bit different in flies.
So what he concluded is that these chromosomes, because
this super rare event was correlated with the behavior
of alleles, these chromosomes are very
likely to contain genes.
And then in fruit flies, whether or not you have a Y
chromosome doesn't seem to be the main determining factor.
In humans, it is.
So humans that don't have a Y chromosome are not male.
So an X human is a female, not a male.
So different organisms do sex differently, as you would
probably guess.
So those are his two main conclusions.
The first one is the really important one for genetics.
The second one is something that he [INAUDIBLE].
So what I wanted to introduce you to is a way of doing
crosses and how you do crosses to figure things out, and also
to bring up this idea of [INAUDIBLE].
So white is not the only thing that's on the X chromosome.
There are a whole bunch of other things that are on the X
chromosome, both in flies and in humans, and that actually
correlates a lot with a lot of the diseases
that we know about.
In fact, one of the first human diseases that we knew
about connected to this chromosome was color
blindness, and that was based on how it was passed down from
mothers to sons.
And people worked that out.
OK, so we talked about a lot of different genetic
behaviors--
lots of ways that different genes could interact with
other, different alleles.
And so we talked about all of these sorts of things last
week and how did this one-- that genes could be inherited
sex-specifically.
And I'm going to start today and then continue a bit more
tomorrow on the very last thing that we're going to be
talking about in terms of how genes can behave.
And this is a failure to assort independently.
So if you understand these 10 things, you basically can
solve any of the problems that they're going to give you in
BIO41 and [INAUDIBLE].
So remember I said in the beginning you try to simplify
things the most simple way that you can.
And you try to work on that.
And then you find out that yeah, in your one simple case,
this is how it works.
But in the real world, things are a little bit more complex.
And this is exactly what happens with an independent
assortment.
So with Mendel looking at pea plants and looking at those
seven traits, he found that every one was completely
independent of the other ones.
So the probability of a particular allele of round or
wrinkled had nothing to do with the yellow or the green.
They were completely independent.
So that was the case for the things that Mendel
happened to work on.
But Morgan is finding that genes are on chromosomes, and
Morgan is also finding lots and lots of different mutants,
lots of different traits.
But only four chromosomes in fruit flies.
And yet Morgan is finding 15 different traits.
So, you have to think about how could those, if they're on
chromosomes, how can they be independent of one another?
And so he brought us into this dilemma, and you can
imagine this here.
So if he's finding that he has all these genes, if there are
more genes than there are chromosomes, then in cases,
you have to have multiple genes on the same chromosome.
So either things don't always assort independently, because
we've already seen how these chromosomes behave, that one
chromosome goes to one daughter, and
one goes to the other.
So either we're going to get a case where if you have-- so if
you look at this chromosome, you have the big X, big Y, and
big Z. So either if you get a big X, you're also going to
get a big Y. It's not going to be independent.
You're not going to get 50% big X and little y.
You're going to get 100% of that.
So either that's going to happen, or somehow, these
chromosomes that he's followed so beautifully
through cell division--
somehow, these chromosomes have to exchange parts of
themselves.
So if you get something that's a big X and a little y and a
little Z, then you have to imagine at some point part of
the information from this chromosome switched over to
this chromosome.
The other possibility is both of these things are true.
And so we're going to walk through some of the
experiments first to look at this, and then down in here to
think about how [INAUDIBLE].
OK so Morgan really likes these traits.
He's looking at eye colors, he's looking at wing shapes,
he's looking at legs, he's looking at whatever you can
look at in a fruit fly.
I don't know how many things there are to look at.
And he's got a couple of things here to follow.
So he's going to look, in this example, at two different
traits, one for the eye and one for the wing.
And he already knows that these are non-sex-linked.
So he did these processes to see how they were inherited,
and finds that they're not on the X chromosome and not on
the Y chromosome.
So if I were to get anyone's [INAUDIBLE].
So he's going to do something, a pretty standard kind of
cross that we see over and over.
So he has two pure breeding strains, so we know that
they're homozygous everywhere.
And these are the designations that are going to be used here
either as pluses versus minuses.
So in the F1s, we're going to get from this pretty easy.
Each parent can only give one type of allele.
So we're going to have something that is pr plus, pr,
vg plus, vg.
So what we expect is that they're going to have the wild
type-- well, actually, we don't know yet what we're
going to-- we need to go and figure out which one's
dominant and which one's recessive.
So he does this cross.
You get something that is--
and when he looks at these, all of them have all of the
[INAUDIBLE].
So that means that they've got red eyes and long wings.
So he's going to do a cross, like you've seen before--
you're probably tired of these crosses by now--
and say, OK, fine, I'm going to look at how these behave
independently of one another by crossing them to another.
To a sibling.
A lot of *** in fly genetics here.
And you'll get some progeny out.
He's going to get a lot of progeny out.
That's the great thing about fruit flies is that you can
produce thousands and thousands of [INAUDIBLE].
And he's going to see what happens.
Am I going to be able to get red eyes with long wings, red
eyes with vestigial wings?
How do they mix them?
And so if we look at what we'd expect in terms of what these
are going to be for genotypes, wild type we're going to have
so that the red and long ones, those are those plus alleles.
Actually, I'm going to take this back.
We're going to do something a little bit different.
This is the one that it got back after.
If you cross them to each other, you can make the slide
little bit easier by crossing it with this one.
So let's go back here.
So from this first one, we have this guy.
We're now just going to carry this one over to the next
[INAUDIBLE] with that female, and then just cross it to
something that's homozygous recessive.
The reason you do that is it simplifies things.
The male is always going to produce the same thing, and so
you really just have to do it with the females.
So the nice thing in here, if we fill out, what the male's
always going to do is going to be very boring because they
always do the same things.
And then we can figure out, based on what we knew from
dominant and recessiveness, that what the alleles are for
the females.
So the wild type are going to be both of those plus alleles.
If it's purple, it's going to have the recessive alleles for
the eye color.
So two prs and the vg plus.
The vestigial, so it's got both of them.
They're probably for both of them.
If it's red eyed and vestigial, it's got the Y type
allele for the eye.
And if it's purple with a normal wing, then it has the
recessive allele for the eye and then the normal
eyes, the normal vg.
And so based on what we knew from typical test crosses,
what we'd expect, if they're sorted independently, that
every time--
so there's an equal probability of having this
mutant allele with this mutant allele or this mutant allele
with this wild type allele, this wild type allele with
this mutant allele.
All of those things should be equal, in an equal quantity.
And so if he has this many progeny, then he's going to
expect that you get those equal numbers.
So you'd expect 710
approximately for each of those.
So that would be evidence that he's got these two genes, and
they're assorted independently.
The problem is, he did not get that answer.
So what he got was this.
So he got a lot of these.
A lot of wild types, and a lot of purple vestigial ones.
Not so many of the red-eyed vestigials, and not so many of
the purple normal wing.
So this is just--
I just color coded these guys so you can see who came from
mom and who came from dad.
So the pink ones-- sorry, it's very stereotyped.
Pink ones for mom, blue ones for dad.
But if you look at what he got, remember, the numbers
here were--
you could sum that up pretty well in saying he got lots of
these and not so many of these.
So do you recognize anything else about the ones he got
lots of versus the ones he didn't get very much of?
[INAUDIBLE].
Yeah.
So if you go back and you remember what the parents were
that went into that cross, so one that had-- because it had
wild type alleles in both of these, so with red eyed and
long wing, and one that was purple and vestigial, you got
a lot of things that looked just like the parents and not
so many things that looked different.
So on Wednesday, we're going to try to figure out why it is
that these four classes of progeny weren't found in equal
numbers, and then what those numbers mean in trying to use
that [INAUDIBLE].