I just got the feedback from the one minute things just a few minutes
before class, so I think I may defer commenting on the couple of them
until the beginning of next lecture. But there are a couple of things
that I think I can say. One is, several people were
wondering, how does the cell decide whether to do mitosis or meiosis?
But the mitosis, which is ordinary cell division is what happens
everywhere in your body, in your intestine, on your skin,
in your eye, anywhere except, since that I you make all the different
cells you have. The meiosis, which creates the sex
sells, or gametes, happens in a very specific place,
either in the testes if you are male or the ovary if you are a female.
So, there's a dedicated place where meiosis takes place,
and just your knowledge of human anatomy and physiology can make a
pretty good guess as to where that is. Everywhere else, it's mitosis.
There's a very special place where that happens. A couple of you still
got confused when I was talking about meiosis and I were showing you
a progression through, and I put a double headed arrow,
meaning that's was with that period was called. The process is
unidirectional. It only goes in one way.
It's not a reversible process. There were some questions about the
chiasmata or the chiasma: why is there a crossover in chiasma in
meiosis but not mitosis? I will tell you about that today
very specifically. Why was there a tall and a short
pair of chromosomes? That was arbitrary. I made up a
simple cell for us to consider these properties in,
one with a long, and what with a short,
nothing else. I wasn't trying to represent any particular organism.
And I'll pick up on a couple of other things. I just want to
quickly mention something. Since I've seen you, I flew out to
San Diego, gave a talk yesterday morning at a major meeting,
hopped on a plane, got back at midnight, and here and again.
As part of being a scientist, come teacher, at a place like MIT,
you guys tend not to see, but my research life goes on
while I'm teaching. And I just want to briefly mentioned
one thing I talked about yesterday, because just in my own life it
captures a couple of things that I've been trying to tell you,
that the textbook is not the ultimate authority.
That's just what we think up until today. A new finding to change the
way you think about things, and what I'm telling you, and some
of your frustrated at, that I'm not just parroting back the
textbook is because this is the way it is. If you guys are going to be
leaders in whatever field you're in, you're going to be dealing with this
process of shifting sands as we gain new knowledge.
So, in fact what I was talking about has some relationship to the cell
cycle that I talked about. Lee Hartwell particularly helped us
understand that there is what's called a G1 phase,
which you could think of as a preparation for DNA synthesis for
what's known as the S-phase where DNA synthesis actually occurs.
And now, you're at 4N. You've doubled the DNA content,
and there's G2 where it cleans up from S-phase, gets ready for mitosis,
and mitosis is what you, then, separate the daughter
chromatids, go back to 2N, and then ultimately the cell divides.
And we are back to 2N. And what we were talking about DNA
replication, I told you how replicative DNA polymerases test for
Watson-Crick shape, and remember that little movie I
showed you where they flipped the base pair into a very narrow slot in
the protein, and they check that it's there. And they said at that
time, that's why polymerases have a problem when they hit a lesion such
as a thymine dimer that we get we go out into the sun.
And then one of the recent pieces of excitement in the DNA repair field
that I work in, was the discovery of a whole class
of translesion DNA polymerases that are very flexible,
active sites and we are able to copy over a lesion.
Right at this point, you will find in the literature all
sorts of reviews about polymerase switching, where people are
envisioning the replicate of polymerase coming along.
It hits a lesion, gets stuck. It recruits one of these translesion
polymerases that comes in, copies of the lesion; it switches
back to the replica of polymerase, [and then it goes?]. And there are
reviews like that coming out in the literature. So,
one of the genes that's needed for this sort of error prone kind of
translesion synthesis in yeast and in humans is a gene called [rev-1?
. You don't have to notice for the exam, this bit.
But if you knock out the function of that gene, the yeast aren't mutated
by UV or chemicals anymore. So, you know it has an essential
function somehow in this process of translesion synthesis.
So, one of our big surprises was I was trying it.
We were trying to actually fish out partners that might interact with it
cause we thought it would be regulated. And we were surprised.
The experiments revealed something we hadn't expected.
We found out that this protein that was critical for mutagenesis was
extremely strongly cell cycle regulated.
Well, given the reviews I've told you, or if somebody you're writing a
textbook today, this is what they would tell you:
polymerase switching during S-phase. So you might have thought it would
be high and S-phase, but it isn't. We can barely detect
it during S-phase. But instead, the rev-1 levels are
at least 50 times in the G2M phase. Actually, it goes right through
this part of the cell cycle, 50 times what they are during
S-phase. And so, there's a couple of
possibilities right now. Either these very tiny amounts that
are doing S-phase are what everybody thinks and current models would
predict: you're getting polymerase switching. And it makes 50 fold
more during this phase for something else. If so, I don't know what that
is. The other possibility is that we have to rethink our model,
and that it isn't polymerase switching during replication.
Actually, the replication for it just keeps moving,
and it leaves behind little masses. And when the cell is busy starting
to line up as chromosomes, and even while it's pulling them
apart, that's when this translesion synthesis stuff comes in,
and it cleans up the damage. Now, I don't know what the right
answer is. That was one of the things I was talking about yesterday
morning. But it's an example of how something that you guys can now
hopefully at least understand in principle is being debated
right now. And the finding from my lab changed
the way I'd been thinking about it at least. I can now see another
very real possibility. So, just to move on, so we are
going back to Mendel now, who did an awful lot more than I
told you. A few of you thought it was pretty frustrating and it had
all that. But Mendel was doing other things. You already know what
he could do. He knew how to do crosses. He knew how to count.
And he could think, which was really important.
And he's our ratios instead of just numbers. So it was another class of
experiment that he could do, and that was he could do a cross
where he looked at more than one trait at once.
And he didn't have all that many options for things he could do,
but he did what are known as dihybrid crosses,
where he followed two traits at once. And I showed you some of the traits
that he studied. In fact, that picture I showed you
is actually a cross that we can think of right now.
He's got smooth, and yellow, wrinkled, and green, and yellow,
and you'll see them in all four combinations. So,
an example of the kind of crust that Mendel carried out,
then, was he took smooth yellow, which actually is the dominant
allele, and [both? , which he learned from his other
crosses. And he crossed it with wrinkled
green, which I'll represent as a little s, little s,
little y, little y, where he previously known the little s and
little y alleles, the wrinkled and green were the
recessive alleles. And then, the F1 generation,
wouldn't be surprising to you at this point, I think,
that they were all smooth, yellow. And, they all were ss yy.
And if you think about the possible gametes you get out of this,
you could only get a big S, big Y out of this one,
and little s, little y out of that one.
So if they came together, it would have to be that. So then,
what he did the self crossed the F1, and what he got out of that was the
kind of mixture of things that he saw there.
He saw smooth yellow, smooth green, wrinkled yellow,
and wrinkled green. In doing the same kind of experiments that we
talked about before, he counted them, he looked to see if
he saw characteristic ratios. He did.
The ratios he saw were 9:3:3:1. So, I think we know how his head
worked at this point. He was try to figure out if he
could explain these results by the kind of model that he was developing
where hereditary information came in, in particles. And he could.
But he had to make a critical assumption.
And if you've just seen the next square going to draw,
without realizing the assumption underlies it, then you've missed a
great deal of his thinking. And that was that the two genes of
sort, or the two traits anyway, because he didn't know they were
genes yet independently. And the way we could see that would
be to think about what were the kind of gametes that you could make from
those F1s. So, we could get a big S and a big Y
from here, or a big S and a little y, or a little s and a big Y,
or a little s and a little y. And, since this is [selfing?
, it's the same thing. So I won't fill this whole thing in,
but we get two S's, two big Y's here. Down here we'd have little s,
little y like that. I'll fill in a couple up here where we've got big S,
big S, big Y, and a little Y. Here we have big S,
big S, but two little Y's. Here we'd have big S, little s,
big Y little y. And over here we'd have big S, little S,
two little y's. So, if you were to make out [then?
a table or a chart like this that showed the phenotypes,
you'll find that all of these wild type, we can see it here.
However, this one would be smooth. But it's got the two alleles. So
it would be green. This one would be smooth and yellow.
And this, again, would be smooth but green.
And down on the corner it is the wrinkled green.
And if you follow that out, draw out the rest of that, you'll
discover there the 9:3:3:1 ratios. That was what Mendel observed in
all of his experiments. But he was particularly bothered by
it because he'd shown particular information. The fact [they sorted?
randomly wasn't an issue. However, that was before people knew about
the chromosomes, which we spent quite a bit of time
talking about the other day. As I said, when people saw those
chromosomes that gave rise to what's known as the chromosomal
theory of inheritance. And what was interesting about
chromosomal theory of inheritance was that it predicted a different
outcome depending on whether the traits you were studying were
encoded by genes on the same chromosome or by genes on different
chromosomes. Now, as it happened, what I think Mendel
did was he found traits that were well behaved and he could study.
And those all happened to be on separate chromosomes.
So, his results didn't disclose this issue that was raised by the
discovery of chromosomes. The chromosomal theory of
inheritance gives, as I said, predicts different
outcomes depending whether things are on the same or different
chromosomes. So let's consider that by taking the
F1. So, say they are on separate chromosomes. And let's take the F1
from the previous cross over here. So, big S., little s, big Y, little
y, and then we'll cross it with the homozygous recessive parent.
That was a cross that I mentioned the first lecture was very important.
It's important enough that it's given a special name.
It's called a test across. Well, here we are using it here.
Well what are the possible outcomes that could come from this sort of
thing? Well, I think the way you could think about it most easily is,
what kind of gametes or sex cells could we get out of this?
Well, from here we could get a big S and a big Y. Or,
we could get a big S. and the little y, a little S and a
big Y, or a little S and a little y. So, we could get four different
types of sex cells. The gametes we can get out of this
sign, there's only one type. So, if we start combining those,
I think you can see what the outcome would be.
It's so simple. We don't even need to draw out the
square. If we had big S, big Y over, they're all going to be
over. Well actually, I'll draw up this way because I
think it's a little easier to see. So, there would be four possible
things that would come out of this test cross.
This would be the smooth and yellow. Here would be, what have I done
wrong here? No, this is right. This should be
smooth and green. This would be wrinkled and yellow.
And this would be wrinkled and green. And, do you see what the
ratio would be? It would be 1:1:1:1 because we have
an equal probability of making any of those.
And, I'm going to rearrange these because the way that it'll help us
think about it, this is one of the types that we've
found in the original cross. That's a parental phenotype,
smooth and yellow. It was one of the parents up there.
This is the other one that looks like one of the original parents.
So, I can divide these into parental or nonparental phenotypes.
These are 1:1, and then these others were ones
where the progeny differed from the parent. And they're all 1:1:1:1.
Now, that's what the chromosomal theory of inheritance would predict
if they were on separate chromosomes. That's what Mendel saw when he was
doing his crosses. What if they were on the same
chromosome? So, we are going to have to go back to
the original cross now to think this one through. So,
what Mendel started with was a smooth, yellow parent.
So that was SYSY. But because these are on the same
chromosome, I'm going to depict them this way so we can see they're going
to travel as a unit. So that was then crossed with the
wrinkled green, which would be a little s,
little y. In each case, [UNINTELLIGIBLE] should be F1 in
this case will be all smooth and yellow.
The recessive traits disappear, but this time they're only, what the
progeny will have, they will have gotten one of the
possible alleles from this one, which would be the SY on the same
chromosome, and one from the other parent, the little s,
little y again on the same chromosome and one from the other
parent, the little s and y, again, on the same chromosome.
So now if you start to ask, what will happen if I do a test cross,
you're going to get a different outcome. So here's the test
cross in this case. So, we've got this F1.
It's smooth and yellow, but it's actually at the chromosomal
level now. It's like this, and we're crossing it with the
homozygous recessive parent that's now going to look like that.
So if you think through, what kind of gametes could we get out of this?
Well, there's only two possibilities.
We could get this one or this one.
And over here, the kind of gametes we could get,
there's only one type. So, what are we going to get out of this cross?
What we'll end up getting is big SY, over the little sy,
or little sy over the little sy like that. That's smooth and yellow,
wrinkled and green, the ratio of these 1:1.
But you see the difference from what we saw before?
These are the parental phenotypes.
The chromosomal theory of
inheritance doesn't predict that you will get, or it predicts that you
will not get the nonparental phenotypes. So,
if you wanted to distinguish between these two hypotheses,
and figure out where your genes were, you'd do the experiment.
And what happened when this was done, again, what often happens in
science, you think you've got it straightened out.
You got hypothesis A and hypothesis B, and you do experiment planning to
do the scientific method and show it. And you get a result that isn't
what you expected with either model. And that's in fact what happened in
this case. And it led to the discovery of
genetic recombination. And to show you actually the
experiments where that was discovered, I'm going to switch to
another widely used genetic model, which is the Drosophila melanogaster,
or the fruit fly, which you see in the summer around
rotting fruit. Or if you're in the biology
building, one is apt to land on your sandwich because there's just a few
stragglers that get out of the Drosophila genetics labs.
But the one thing you can see from this is the eyes,
pretty cool. It's got red. The wild type is a red eye,
and the body's brown. And, you can see the red eyes.
If you look at a fruit fly carefully, you'll be able to see,
the summer if you take a look, you'll see that they have red eyes.
So, they've been a very useful model organism for genetics partly
because they grow pretty fast and they are easy to handle in a lab.
And so, I'll introduce you to a couple of features.
So, the wild type you find in nature is a brown body.
We'll call it a plus, and it has normal wings, and which I'll refer
to as plus. And some mutant phenotypes that geneticists have
been able to find is a black body which I'll refer to as little b.
And vestigial wings, which I'll refer to as VG.
So, these are fairly easy to score. They look like little tiny wings.
It's fairly easy if you're crossing Drosophila, and that looking at
progeny to go through and score, what color are their eyes? And do
they have ordinary wings or little wings?
So, this is the kind of cross that was carried out.
We are going to switch now to an organism that has male and female.
Up until now, plants are both. They make pollen,
and they have the eggs that are going to develop into the seeds once
they're fertilized. But, Drosophila are more like us.
They come in males and females. So, we're going to have to specify which
is which. And I think most of you are probably familiar with
this terminology. This is the symbol geneticists use
for female. And this is the one that is used for male.
So, in this case, let's set up exactly the same kind of thing that
we start here. We're going to cross a homozygous
parent versus a homozygous recessive parent. That's just exactly the
kind of thing we have up here. But I'm going to do at this time
using Drosophila genetics speak. And so, we'll be taking female whose
wild type for both traits, we're going to cross with a male
that's homozygous recessive for both traits. This is the way Drosophila
geneticists tend to represent this kind of thing.
So it's exactly the same kind of cross we got before.
And at this point, what we get out of the F1, it shouldn't
be news for you. You can see genetically what it's
going to be. They'll have to get one allele from here,
one allele from there. So, by definition, the only
possibility that you can get out of this, the F1s,
will all have one allele dominant, and one recessive allele just like
up there. And this will be, since the wild type is the dominant
allele, this will be brown and normal, and normal wings.
And then, at this point they then will set up a test cross,
exactly the same idea. We're going to take the F1.
And in this case, we'll take a female whose got this,
and we'll cross her with a male who is homozygous recessive.
So that will be black over black, and vestigial over vestigial. And
out of this, there are four possibilities.
We can get parental phenotypes. So, there will be, from that, black
over, if you look to the various combinations of how these things
could go together, you'll find we can get vestigial
plus. Or, we can get black over black,
and vestigial over vestigial. For example, this one,
coming from those two getting together, and this one coming from
this one and this one getting together. So this is just exactly
the same kind of thing we've done but done using Drosophila traits.
And then, nonparental, so now we get, for example,
black over black, and vestigial over plus, black but normal wings,
or we could have black over plus, vestigial over vestigial, which
would be a brown body, but with vestigial wings.
So, if we were trying to do this kind of cross,
we are doing this kind of cross, and we are trying to see what the
outcome would be, Mendel, every trait [assorts?
independently would predict the 1:1:1:1. And the chromosomal theory
of inheritance would predict we'd get 1:1 here, and we wouldn't see
those at all. Instead, what happened when this experiment
was done where numbers that didn't really fit.
This part works pretty well. These are numbers from an
experiment of this type. So these are pretty close to 1:1.
That's OK. That fits with both of the models. The surprise is over
here where there is [2/6 to 185? . So, these are in the ballpark of
1:1. But what you can see is the result is not what was predicted
by the model. This is the kind of thing I've sort
of been trying to tell you through the course. It keeps happening in
biology. It's not a QED sort of thing where you can work it out by
logic. Very often, you do an experiment,
you get a result that doesn't fit within your current framework.
And then you have to go back and redo your thinking.
So what was going on here, as it turned out, and it all got
sorted out, was scientists had just discovered genetic recombination.
And here is where, what was going on. So when we
talked about Meiosis I, and we had duplicated the DNA,
so we now had to chromatids, and I showed you the chiasma when it was
drying, it looked sort of like this.
And, I said that you always sought these physical attachments that once
the homologous pairs were duplicated, they would always be in contact.
And I said there was actually a physical interaction going on there.
Well what was going on in there was an exchange, a recombination event
at the DNA level that's just exactly equivalent to what was happening
when I showed you the phage cross.
Remember, we had a phage cross, and if we got a recombination in
between the two genes, then we could get progeny that were
a mixture of the two traits. So, if we were plus plus, for
example, these are on the same chromosome. And the other one is
like this, black, vestigial, black, and vestigial.
If we get a genetic recombination going on here where these two
intersect and recombine in between these two genes,
what you get out of that, then, is this chromatid is still the
same. It's got both wild type alleles. But in this case,
now, the black allele has moved from here to the tip of this one,
pairing it with that. And the other chromatid over here,
the other homologous pair, now has the plus together with the vestigial
here and then here. So, if you, then, draw out the
possible gametes one will look like one parent. One will look like the
other parent. This one can give rise to a nonparental phenotype in a
test cross. And that one can give rise to a nonparental phenotype
and a test cross. And that's what's going on in this
experiment I've described. But the nice thing about this since
this sort of thing is happening is one can calculate,
then, a recombination frequency in just the same way that we calculated
it when we were doing phage cross. And in this case,
it was the recombinants, which in this context I'm referring
to the nonparentals, the recombinants over the total of
the parental types and the nonparental.
So in this case, this would be 206 plus 185 over 965
plus 944 plus 206 plus 185. And if I haven't blown the
arithmetic, that would be a recombination frequency of 17%.
Now, we were back talking about that phage cross.
Remember, we did a pair of crosses between gene one and two,
and between two and three, and then we were trying to figure
out if they were in the linear order, how we could explain it.
And we finally worked out the order by crossing allele one and three.
And we made a little genetic map that could show the order of gene 1,
2, and 3, based on nothing more than the recombination frequency.
So, that's exactly what people were able to do by this kind
of measurement. And that, then,
led to the generation of chromosome maps. This is a publication from
Science in 1994. This is before the human genome was
done. And they were mapping a kind of genetic marker that we'll talk
about [when?] we do restriction enzymes. But they were able to
associate it with [banning? patterns they had seen on the
chromosome. This is the sort of thing that
cytologists saw, and as scientists were working this
out, then they were able to associate these genetic maps of loci,
and begin to associate them with the physical maps of banning patterns
[in?] chromosomes. Now we have the sort of ultimate
genetic map, which is the sequence of the human chromosomes.
So now we know exactly, to the base pair, how far different genes are.
Part of the way that the human genome was assembled from all these
little tiny fragments of DNA that were sequenced were taking advantage
of these kind of maps that told the scientists assembling all these
little fragments of DNA sequence what order they had to be in,
what part of the chromosome they were on, and that kind of thing.
There is, this, then, leads us, though, to other issues since I've
now started to talk about chromosomes. And one more thing,
let me just say before I leave this. So, from this kind of thing,
if the recombination frequency is much less than 50%,
then they're on the same chromosome. And the word geneticists use to
describe this is they say genes are linked. If the recombination
frequency is 50%, then they are on different
chromosomes. At this point,
it's just random assortment. [You go?] one way or the other [as
you get?] a number of 50% if you do this kind of calculation.
And these are referred to as unlinked. And those of you who are
thinking about it can probably imagine that there might be a
problem, that if you had a very long chromosome, so the two genes you are
studying were very far apart, you might get so many recombination
events in between that it would begin to look,
the recombination frequency might come close to 50%.
And you would perhaps have a difficult time in that genetic cross
telling whether the genes are really unlinked. They were on separate
chromosomes, or they were linked but very far apart.
So this kind of thing could be a little hard to resolve that kind of
situation. But there are other things you can do to look at that.
So, the chromosomes we've been talking about are what are
known as autosomes. These are identical pairs.
But there's an exception. And those are the genes that are
involved in sex determination. It's the chromosomes that are
involved in sex determination. These are known as heterozomes.
And, they're on this picture that I showed you where they used this
technique of chromosome painting to show it.
You can see how all these autosomes are in identical pairs.
But this is a male, obviously, because there's the Y-chromosome,
and there is an X. If you're a female, you'd have two copies of the
X, something I think most of you know. So, if we think about how
this works in humans, females have two X's, and males have
an X and a Y. In Drosophila,
the fruit fly, it's the same thing. Males have two X. Females have two
X's, and males have an XY. But there isn't anything magic in
nature about females having two of the same, and males having one of
each because in birds where it's different enough they use
different notation. The females have one of each.
And let me make sure I got my notation right.
I think it's ZZ, excuse me. And the females have one
of each. So, nature tends to use these differences as far
as sex determination. And this, then,
poses a new kind of problem. And that is, what would happen if
you were doing a cross, and the allele that you are studying
happened to be a sex chromosome instead of one of these?
You might guess that since females have two of one and males have one
of each that I would not give the results that are predicted by what
we've talked about so far. And so, this led to the discovery
of what's known as sex linkage. And that's important.
And in fact, as you'll see in a minute, affects stuff that we are
familiar with in our lives. I want to just quickly introduce
you to this, and show you how it was discovered. It was done by Thomas
Morgan in 1910 actually, this discovery. What he was doing
was he took a white eyed male, crossed it with a red eyed female
wild type, and yet the expected result that the F1s
were all red eye. But then when he took the F1 female,
which was red, and crossed it with a red eyed male,
you got something that was very puzzling at the time.
The females were all red. The males, half of them had red
eyes, and half of them had white eyes. If you followed the logic up
until now, where you try to work this out, you would find that you
couldn't generate this pattern by the stuff that we've talked about
now. So once again, this led to the need to create a new
model, something that expanded our thinking.
So, the way the thinking went was, well, there must be something to do
with the sex of the fruit fly in this. And so,
here was the hypothesis, and that was that the white eyed
male had this genotype. They had an allele that caused the
white eyeness. But it was located on the X
chromosome so that the male would have had a Y chromosome
paired with that. And, the red eyed female used in the
first cross would have a wild type allele on both X chromosomes.
And so, if that were the model, what's going to happen to them when
we do this cross that we've described here?
Well, let's think it through. So, we've got female whose X plus.
We're crossing with the male who's
got the X with the white allele over the Y. So, the females can either
be, they'll get an X plus XW, and the males, yeah, right.
The males are going to get, they will get this allele for Y.
So now, if he takes us red eyed female, that was the F1 from the
cross up here, which will be this,
and crossed with a red eyed male. Now, that means the male has to
have the good allele. What are we going to get?
Well, for the females in this cross, we've got a couple of possibilities.
This one, we could get just the wild type female back,
or we could get this one pairing with this one,
which will give us this. So, these are all red that fit.
But, the males, then, if you see what happens,
they have to have, each have to have a Y, and then they can either get
this allele or that allele. If they get this allele, they're
red. If this allele, they're white. If you stand back
and look at that, you will see that is the outcome
that was observed. Females were all red.
The males are half red, half white.
Well, this is a characteristic of, this would be an X-linked trait.
And I want to just point out one thing. This female,
excuse me, wrong female. This female here is what's referred
to as a carrier. She's got this allele that causes a
white guy, but she's not expressing it herself.
But she's able to transmit it to her sons. And when she has progeny,
on average, half of her sons will have the trait.
And now, X-linked traits, there are a number of them that we
know about. Some of you may know hemophilia. Queen Victoria was a
carrier of this gene causing hemophilia, where there is a problem
with the clotting mechanism. And if you get a cut, then you can
bleed a lot. So, some of her sons had this.
A more common one, which has to apply to some people in this room,
is red-green color blindness. If you're a male,
you have a much higher probability of being colorblind because it's an
X-linked trait. And I want to just close by showing
you how human geneticists think about the sort of thing.
And we have to think about things differently if we are doing human
genetics because as most of you know, I think all of us would be very
uncooperative subjects in a kind of genetic cross that a fruit fly
geneticist [or most? geneticists would like to have us
do, in which we'd be put in a cage with a member of the other
sex and say, mate. That was your choice in life.
Well, that would be a different kind of existence for us all.
So, human geneticists don't have that luxury of having pure breeding
strains and doing controlled crosses.
We all have very strong feelings about the kind of crosses that we
want to engage in. And so, what they have to do,
they have to make use with what they find. And they use a couple of
symbols here that I'll just show you. They look at pedigrees,
and then they look for patterns. And, they use a little shorthand
for doing this. Males are squares,
which I don't know if there's any symbolism to that or not,
but if they are affected they show it as a shaded square,
and unaffected as an open symbol. So, affected males are solid squares.
Affected females are solid circles. So, let's take a look at the sort
of pedigree that human geneticists might see. And let's consider
something. Let's consider red-green color blindness,
which is an X-linked trait. So, let's take a male, which there
is probably one in this room at least, maybe more, who have this.
So, since the colorblindness trait is on the X chromosome since he's a
male, the other pair will be Y. That means if you're a male and
you've got it, you're going to display the
phenotypes. So this is, George, let's say, who is colorblind.
They leave a lot of the romance out of these things,
as you'll see, who had progeny with Mary. Let's say,
they got married after they graduated from MIT.
It was very happy. They had a, let's see,
son. He had to get the Y from dad. So, he had to get a good allele
from his mother. But they also had a daughter,
and she had to get the color blindness allele on an X chromosome
because the dad only had one of them, and then a good one from her mom.
So at this point, everybody's normal.
But you'll notice, this daughter has this trait of being a carrier
because even though she doesn't display the trait herself,
she's got it in her genome. So, let's say, [UNINTELLIGIBLE
PHRASE], a woman who doesn't have any colorblindness allele.
So, if we have, let's say, a daughter,
and a son, a daughter, and a son, this is not much happening over on
the part of the pedigree. Everybody would be normal.
Yeah, did I miss something? Pardon? Oh, it's over Y. Excuse
me, yep, I'm going too fast here. Over Y, here we go. I don't need
to introduce any genetic abnormalities on top of what we're
already trying to do here. This is complicated enough.
OK, so what happens, let's say then that the daughter
that married a guy, and they had four children.
I'm going to help us with the genetics of it,
from the geneticist, that sort of a perfect family in
this case would be four kids representing all four possibilities.
And so, first off let's think what would happen with the daughters.
Well, the daughters could either have the colorblindness allele
paired with this one. Or, they could get a wild type
allele with this one. So actually, I'd better put this in.
So this is a daughter. So this would be [CB?] over plus,
or it could be plus over plus. This one would,
again, be a carrier. Now, with the sons, they're both
going to get the Y since they're male. But there's a possibility of
either getting the good allele, which means he'll be unaffected.
But, if you get the other one, he'll be affected.
Now, this would be sort of a typical pedigree. And you realize,
depending on the number of kids, you might or might not see this.
But this, you're going to get to do some more of these and to do some
other traits. But let me just sort of point out, if you're a human
geneticist, what you would recognize here, the trait's more frequent in
males. The frequency of color blindness is about 8% on the X
chromosome. So, if you're a female,
you've got to have two of them. So that means, you've got 0.64%
because you've got to get two together. It's a much smaller
probability. The trait skips a generation, [you'd often say?].
You see it here. You see here. But you don't see it
in between, and that's because you have this carrier.
The affected males don't transmit to their sons because what they give
to their sons is the Y. So, they [kept giving?] the
colorblindness thing. And then, the heterozygous females
who are carriers will transmit the trait to their sons about half the
time. And that's a pattern that a human geneticist would look for.
And they'd say, ah-ha, it must be an X-linked trait.
And you'll see in your problem sets and [recitation?
sections are the patterns. OK, I'll see you on Friday.