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Good morning. Good morning. Yes.
So I want to pick up where we

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were last time. We talked
last time about Mendel's

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elegant experimental design.
And not just elegant but very

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careful, too, in having
organisms that bred true.

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And a lot of work went into that.
We talked about his observations

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and his really great choice to count.
We talked about his ability to look

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at numbers that were approximate and
somehow intuit what was interesting

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about them. Namely, he had
to take rough numbers and say,

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hmm, I think this is a 3:1 ratio,
although that was an abstraction,

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but a very good on his part. And
it's hard to know when to make

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those leaps and when you're kidding
yourself, but Mendel got a lot of

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data. I didn't mention that
he worked on not just round and

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wrinkled, but he worked on seven
different traits across pea plants.

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All seven showed these
very consistent properties.

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There was a recessive and a
dominant phenotype and then a

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first-generation. The
dominant phenotype by

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definition was
evident in full force.

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And in the second-generation
we saw 3:1 segregation.

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He felt pretty good about that.
He made other predictions based on

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this. And he was able to put
together a very coherent story.

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And, as I also explained last time,
it sunk like a stone because it was

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an utterly abstract story,
the idea that there were these

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particles of inheritance,
factors of inheritance. You

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couldn't put your finger on them,
and people hate stuff you cannot put

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your finger on. They
say it's just a model.

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Well, as I mentioned last time,
the discovery of chromosomes in

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cells really laid the foundation
for the beginning of a rebirth of

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interest in Mendelism,
in Mendel's ideas. And the

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interesting part of that
characterization of chromosomes was

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the choreography that we
talked about last time.

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That normally in cells undergoing
mitosis, normal mitotic division to

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make more and more cells,
when you stained the cells and

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looked at them before they went
into mitosis you saw these X-like

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structures. However many there were,
they lined up along the midline of

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the cell. They appeared then to
sometimes you could even see them

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kind of attached to
something pulling them back.

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And they would pull back to
make two cells each of which

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had half of the X.
Somebody asked last time,

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I drew four chromosomes, was that
because cells have four chromosomes?

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And the answer was no. It's
because I had room to draw four

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chromosomes in that cell.
And so this time I drew six

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chromosomes to indicate that
you can have different numbers of

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chromosomes. They are usually,
but I should note not always, an

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even number of chromosomes in
higher organisms. But anyway.

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So I drew six this time. And
what's interesting was this

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meiosis. The generation of
sperm and eggs, for example,

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in animals, they are the
chromosomes lined up with a different

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choreography. They lined up in
pairs. And where you could see

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differences in the shapes of
chromosomes, like maybe the little

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crossing point was lowered down
or the chromosomes were shorter in

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length, there would appear
to find their own partner,

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the one that had the same basic
shape. And they would line up in

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pairs. And then they would
undergo a series of two divisions,

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a meiotic one division, meiosis one
and a second division, meiosis two.

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And in meiosis one you would
get one copy of each pair.

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Then it would undergo a second
round of division that looked very

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much like mitosis where these X
structures would be split into two

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pieces. The notion then that pairs
would go to singletons and then upon

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fertilization singletons would
come together to reconstitute a pair

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really did fit Mendel. And
thus was born the Chromosomal

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Theory of Inheritance. So,
whoops, the Chromosomal Theory

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of Inheritance. Are
you overwhelmed by the

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Chromosomal Theory of Inheritance?
Have I given you overwhelming

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evidence to believe
it? No. How come?

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It seems natural
to you now.

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But, I mean, you know, the only
evidence is that there's something

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else that has got pairs in cells,
right? What's to say that some

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other thing that pairs up in cells
actually is the carrier of genes?

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The Chromosomal Theory of
Inheritance is that Mendel's

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abstract factors, genes
live on these chromosomes,

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are these chromosomes, or
something like that. They're carried

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by these chromosomes. And
simply the fact that the

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choreography of the
chromosomes is not the same, oh,

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sorry, is the same as the
choreography of Mendel's genes,

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that's correlation. In fact,
it's ex post facto correlation.

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I didn't have any prediction that
these chromosomes would do it.

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I just saw that the
chromosomes did it and I said,

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OK, you know, that could explain
Mendel's observations about genes.

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And there's a world of difference
between that could explain,

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that is consistent with the data,
and that presents a compelling case

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that this is true. So
there were some people who

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immediately bought into the
idea of the Chromosomal Theory of

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Inheritance, and there were other
people who remained great skeptics

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about this, that these chromosomes
were themselves quite irrelevant to

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inheritance. And indeed many
people who, at this point,

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the early 20th century, felt
that the whole business of

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genes was still not such
an overwhelming idea anyway.

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And trying to unit these
two was going a bit far out.

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So now I have to bring you back
to some of the things that we left

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unresolved last time, which
is Mendel's Second Law of

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Inheritance. Because if we're
really going to start building a

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case that chromosomes really do
carry genes then we better get some

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serious consistency with much more
complex aspects of the theory or we

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better look for some contradictions.
So you recall, and I mentioned,

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that Mendel studies
seven different traits.

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Two of them, roundness and greenness,
both dominant phenotypes underlain

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by these hypothetical genes, big
R, big R, big G, big G, and the

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recessive traits associated
with these same genes,

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wrinkled and yellow, little
R, little R, little G,

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little G. When you make a
first-generation cross what

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do you get? Sorry?
You get round and green

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phenotypically. And
genotypically what are they?

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Big R, little R, big G, little G,
right? That would be the genotype.

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These organisms would
be heterozygotes.

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In fact, they would be
double heterozygotes.

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They'd be a heterozygote for the
gene that controls shape and they'd

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be heterozygous for the gene
that controls seed color.

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OK? Now, suppose we do a cross
back to RRGG, the parent that has

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the recessive phenotype
for both of these traits.

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We're practicing our words here,
right? What will this parent, the

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second parent contribute in its
gametes? What will the gametes from

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that parent be?
Little R, little G.

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They have to be little R, little
G because that's all it's got

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to offer. So
little R, little G.

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OK? What will this parent
contribute? It could give a big R,

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big G. Could give a little
R, little G. Could give,

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in principle, a little R,
big G or a big R, little G.

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In theory any of those are
possible. And what's the ratio

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that Mendel reports?
1:1:1:1:1, so equal.

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That's right. 1:1:1:1. That's
the independent assortment

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of traits. That's what he calls
this. Independent assortment

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of traits.

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That is to say the inheritance of
round and the inheritance of green

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are uncorrelated to
each other, right?

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Knowing which one you got for
roundness, which one you got for

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greenness, they don't convey
any information about each other.

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So how could we explain this in
terms of Chromosomal Theory of

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Inheritance? Well, we could
explain this in terms of

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the Chromosomal Theory
of Inheritance by saying,

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for example, that in this
heterozygous parent here big R and

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little R were carried on chromosomes
that paired up with each other,

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homologous chromosomes. And
big G, little G were carried on

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a different pair of homologous
chromosomes in my meiosis picture

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there. OK? So if that was the
case then when these chromosomes

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segregated in the first meiosis step,
meiosis one, it might be that big R

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and big G were on the left side.
It might be big R and little G were

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on the left side. It might
be that little R and big G

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were on one side, etc.
Because these are different

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chromosomes. They could have
chosen to line up in different ways.

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That's all cool. So Mendel's
Law of Independent Assortment is

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consistent with the Chromosomal
Theory, except we pointed out last

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time, except if big R and big
G were on the same chromosome.

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Then we'd have some explaining to
do. So maybe Mendel was just lucky and

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big R and big G happened to
be on different chromosomes.

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But what if he takes a third
trait? Well, maybe the reason he got

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1:1:1:1 for those traits was it
was also on a different chromosome,

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a fourth trait. And I said
he studied how many traits?

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Seven traits. If they all gave
1:1:1:1 assortment they'd all have

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to be on different chromosomes.
How many chromosomes do peas have?

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How many pairs of chromosomes
do peas have? Seven.

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Very interesting. He might
have just gotten lucky.

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In fact, he did. We know that.
They are on different chromosomes.

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Though, it makes you wonder whether
maybe he had an eighth trait that

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did something funny and decided
not to put it in this paper.

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I don't know. It's interesting.
Like I say, there's choice involved

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in what you want to report at what
point here. So suppose we instead

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had big R and big G, little
R and little G happen to have

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been on the same chromosome. Then
they would have been inherited

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from the common parent here,
say from here into the F1. The F1

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would look like this.
If they were on different

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chromosomes it would look like this.
If it were from the same chromosome

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it would look like this.
And now let's make a little

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scorecard of what's going to get
passed onto the next generation.

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We've got the possibility that it
will pass on. This one could pass

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on. Oh, let's keep score. Big
R, big G could get passed on.

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Little R, little G could get passed
on. Big R, little G could be passed

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on. And little R, big
G could be passed on.

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And if they are on different
chromosomes we expect a quarter,

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a quarter, a quarter and a
quarter. But if they're on the same

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chromosome what do we expect?
What will come out of this? Either

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you're going to get this, in
which case you get both big R and

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big G, or you're going to get this
one, in which case you get little R

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and little G, a half,
a half, zero, zero. Ooh,

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that's very different. What
is Mendel's Law of Independent

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Assortment say?
It favors this.

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But Mendel's Law of Independent
Assortment cannot possibly be right

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if we see this. So Mendel
didn't observe this.

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But if we really believe this
Chromosomal Theory we would expect

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to see it eventually. So
who's going to be right,

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Mendel or Chromosomal
Theory? You vote for both.

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How many vote for Mendel?
How many vote for Chromosomal

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Theory? How many vote for both?
How can you have both? The data

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would be contradictory.
How many vote for neither?

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Hmm. OK. Fine. So we have
a very different prediction.

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Notice that these are the
parental types of chromosomes.

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They're the ones that went into
the cross in the first place,

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big R and big G. These are the
non-parental types of chromosomes.

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They're the ones, they're the
combinations, a big R and a big G

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that didn't match either of the two
parents. That's a new combination.

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Well, it took a while
before folks sorted this out.

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And it was eventually
sorted out in fruit flies.

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And it is, of course, the
case that neither Mendel nor

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this strict prediction from the
Chromosomal Theory turns out to be

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correct. Mendel's Law of
Independent Assortment does not hold

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for all traits, but this
very rigid model of two

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alternatives does not hold either.
So let's take a look at some real

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data. The data comes from Thomas
Hunt Morgan, a developmental

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biologist who eventually became
one of the great geneticists of the

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century at Columbia. He
was at Columbia University

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studying fruit flies. And
he studies fruit flies rather

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than peas. Can you think of any
good reasons why it would make sense

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to study fruit flies rather
than peas? Sorry? It has four

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chromosomes instead of
seven. No, four, seven.

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Anybody been to Columbia University?
I mean where are you going to plant

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peas, right? [LAUGHTER]
I mean it's in Manhattan.

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Also, what else is
wrong with studying peas?

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They take too long. How
many generations of peas are

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you going to get a year in
Manhattan? Not so many. Fruit flies,

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how long do they take? A couple
weeks. You get a generation every

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couple weeks. If you actually
want to write some papers.

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I mean if you have a day job as a
monk, you can do these pea things

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that take a long time. But,
for example, if you were

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trying to get tenure at Columbia,
you might want to actually do

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something that you could get a
couple generations every month or

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something like that. So the
fruit fly was much better.

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They also, you know, they
don't take fields and things.

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You grow them in little vials
with some food at the bottom,

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some yeast medium at the bottom and
a little cotton stopper at the top.

219
00:16:57,000 --> 00:17:01,000
And, you know, it's very convenient.
You can grow zillions and zillions

220
00:17:01,000 --> 00:17:05,000
of fruit flies. So that's
why the fruit fly was

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00:17:05,000 --> 00:17:10,000
chosen, easy, short generation time,
etc. And there are a lot of natural

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00:17:10,000 --> 00:17:14,000
variations out there.
Geneticists love to choose

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00:17:14,000 --> 00:17:18,000
organisms that are just easy to work
with so you can do a lot of work.

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00:17:18,000 --> 00:17:23,000
And fruit flies do have four
chromosomes. So N equals four.

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00:17:23,000 --> 00:17:27,000
That is four pairs of chromosomes.
So he set up a cross. The F0 cross

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00:17:27,000 --> 00:17:32,000
was between a normal fly.
And the way we say normal in

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00:17:32,000 --> 00:17:36,000
genetics in wild type. OK?
Wild type. That is the type

228
00:17:36,000 --> 00:17:40,000
in the wild. It actually doesn't
mean that it is the type in the wild.

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00:17:40,000 --> 00:17:44,000
It means it's whatever type the
geneticist has chosen as his or her

230
00:17:44,000 --> 00:17:48,000
reference strain, but
it's called wild type.

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00:17:48,000 --> 00:17:52,000
And he set up a cross
between a wild type fly,

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00:17:52,000 --> 00:17:56,000
by a fly that had two interesting
properties. Its body was black and

233
00:17:56,000 --> 00:18:00,000
its wings were in bad shape,
and they were called vestigial.

234
00:18:00,000 --> 00:18:04,000
You know, these funny little
wingy things that didn't' work,

235
00:18:04,000 --> 00:18:07,000
hadn't grown out right, etc. So
instead of the normal fly body

236
00:18:07,000 --> 00:18:11,000
color, which is kind of a tan around
its middle, it was black all around

237
00:18:11,000 --> 00:18:15,000
its middle and its wings were very
short. The hypothesis is that there

238
00:18:15,000 --> 00:18:18,000
were genes controlling. And,
in fact, by demonstrating

239
00:18:18,000 --> 00:18:22,000
Mendelian Inheritance black was
a single Mendelian trait which was

240
00:18:22,000 --> 00:18:26,000
recessive to the normal body color,
vestigial was a single Mendelian

241
00:18:26,000 --> 00:18:30,000
trait which was recessive
to the normal body shape.

242
00:18:30,000 --> 00:18:34,000
And the genotype of wild
type was homozygous normal,

243
00:18:34,000 --> 00:18:38,000
which I'll write as plus over plus
now. Geneticists actually prefer

244
00:18:38,000 --> 00:18:42,000
these plus terms rather
than big Rs and little Rs.

245
00:18:42,000 --> 00:18:47,000
Plus over plus. And we'll
take a female and we'll

246
00:18:47,000 --> 00:18:51,000
cross her to a male who is
homozygous for the gene that

247
00:18:51,000 --> 00:18:55,000
controls the body color there and
this gene that controls wing shape,

248
00:18:55,000 --> 00:19:00,000
and we'll look at the
offspring. So makes F1.

249
00:19:00,000 --> 00:19:05,000
The F1 have what genotype?
They're plus over black, plus over

250
00:19:05,000 --> 00:19:10,000
vestigial F1. OK? So then
what he does is he takes,

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00:19:10,000 --> 00:19:16,000
say these males, and he crosses them
back to these flies here that have

252
00:19:16,000 --> 00:19:21,000
the doubly recessive phenotype
doing what we call a test cross.

253
00:19:21,000 --> 00:19:27,000
That's now the name. We're
beginning to introduce

254
00:19:27,000 --> 00:19:32,000
more of these names. A test
cross, when you cross back to

255
00:19:32,000 --> 00:19:36,000
the homozygote for the recessive
phenotype. And what he gets out,

256
00:19:36,000 --> 00:19:41,000
the same exact picture I drew
before, but we're just getting used to

257
00:19:41,000 --> 00:19:46,000
nomenclature and getting used to
slightly different nomenclatures

258
00:19:46,000 --> 00:19:50,000
here. He could either get, he
always got black, vestigial,

259
00:19:50,000 --> 00:19:55,000
black, vestigial, black, vestigial
from the parent on the right.

260
00:19:55,000 --> 00:20:00,000
And here he could get plus, plus,
he could get black, vestigial, he

261
00:20:00,000 --> 00:20:04,000
could get black, plus
or he could get plus,

262
00:20:04,000 --> 00:20:09,000
vestigial. And, as
we said over there,

263
00:20:09,000 --> 00:20:14,000
the predictions would be that if
these were on different chromosomes

264
00:20:14,000 --> 00:20:19,000
he would get 25%, 25%, 25%,
25%. If they were on the

265
00:20:19,000 --> 00:20:24,000
same chromosome under a very simple
interpretation of the Chromosomal

266
00:20:24,000 --> 00:20:30,000
Theory of Inheritance, he
would get 50%, 50%, zero, zero.

267
00:20:30,000 --> 00:20:38,000
And, in fact, what did he get?
965, 944, 206 and 185. What do you

268
00:20:38,000 --> 00:20:46,000
make of it? Which theory
is confirmed? Neither?

269
00:20:46,000 --> 00:20:54,000
Well, maybe this is just
a statistical fluctuation

270
00:20:54,000 --> 00:21:04,000
around the
first line.

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00:21:04,000 --> 00:21:08,000
You don't think so?
How come? Way too wild.

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00:21:08,000 --> 00:21:12,000
But, I mean, these are wild type
so maybe. [LAUGHTER] So do you think

273
00:21:12,000 --> 00:21:16,000
those numbers are too far off,
a quarter, quarter, quarter to be

274
00:21:16,000 --> 00:21:20,000
believable? Ooh. Not
only are they way off 25%,

275
00:21:20,000 --> 00:21:24,000
25%, 25%, 25%, but something is
fishy. The two parental types are

276
00:21:24,000 --> 00:21:28,000
much higher than the
two non-parental types.

277
00:21:28,000 --> 00:21:32,000
That's saying something
to you. Oh, interesting.

278
00:21:32,000 --> 00:21:35,000
What about this other one, 50%,
50%, zero, zero? Could this be

279
00:21:35,000 --> 00:21:38,000
a fluctuation around zero? No.
This one is really pretty easy

280
00:21:38,000 --> 00:21:41,000
to reject because zero, this
is not like close to zero.

281
00:21:41,000 --> 00:21:44,000
This should be zero. You
shouldn't see any of those,

282
00:21:44,000 --> 00:21:47,000
right? Because they didn't go in
if they were on the same chromosome.

283
00:21:47,000 --> 00:21:50,000
So what are we going to do?
We're acting like Mendel,

284
00:21:50,000 --> 00:21:53,000
good. We're seeing something
funny in the data here.

285
00:21:53,000 --> 00:21:56,000
You even saw something that is
beyond just, it's a little weird,

286
00:21:56,000 --> 00:21:59,000
but it's actually a little weird
in some interesting direction.

287
00:21:59,000 --> 00:22:02,000
How many of them are
of the parental type?

288
00:22:02,000 --> 00:22:06,000
Well, it's 965 plus 944. How
many are the non-parental type?

289
00:22:06,000 --> 00:22:11,000
It's 206 plus 185. So let's
figure out what's the proportion,

290
00:22:11,000 --> 00:22:23,000
the frequency of
non-parental types.

291
00:22:23,000 --> 00:22:37,000
Well, it's 206 plus 185 over
206 plus 185 plus 965 plus

292
00:22:37,000 --> 00:22:46,000
944, which is 17%.
OK, so it's 17%.

293
00:22:46,000 --> 00:22:52,000
We now know what the answer is.
When you take two traits and you

294
00:22:52,000 --> 00:22:57,000
cross them in this fashion, two
recessive traits and do a test

295
00:22:57,000 --> 00:23:03,000
cross, the ratio will neither be 25%,
25%, 25%, 25% or it's not going to

296
00:23:03,000 --> 00:23:09,000
be 50%, 50%, zero, zero. In
fact, it will always be 17%.

297
00:23:09,000 --> 00:23:16,000
Why not? But Mendel looks
at his data, and he said 3:1.

298
00:23:16,000 --> 00:23:23,000
It's trying to say 3:1.
Isn't this trying to say 17%?

299
00:23:23,000 --> 00:23:30,000
Yeah. Well, see, that's the thing,
is what to make of this number.

300
00:23:30,000 --> 00:23:33,000
What does this 17% mean? Now,
of course, you all know that

301
00:23:33,000 --> 00:23:36,000
this is genetic recombination,
right? You know that these

302
00:23:36,000 --> 00:23:39,000
chromosomes are exchanging material.
I cannot kid you about that. But

303
00:23:39,000 --> 00:23:42,000
put yourself in the days of Thomas
Hunt Morgan looking at these data

304
00:23:42,000 --> 00:23:45,000
and trying to figure out what
is this 17% trying to tell him.

305
00:23:45,000 --> 00:23:48,000
There were people around Columbia
and elsewhere who were saying,

306
00:23:48,000 --> 00:23:51,000
oh, this 17% number says a lot about
physiology. It's a statement about

307
00:23:51,000 --> 00:23:54,000
the developmental relationship of
genes. And they were trying to read

308
00:23:54,000 --> 00:23:58,000
all sorts of things
into these numbers.

309
00:23:58,000 --> 00:24:02,000
The first thing is let's test
some more pairs of traits.

310
00:24:02,000 --> 00:24:07,000
How about another pair? If
you do that, do you get 17%?

311
00:24:07,000 --> 00:24:11,000
No. It turns out maybe you get 8%.
You do it with another pair, maybe

312
00:24:11,000 --> 00:24:16,000
you get 9%. So it's not a constant.
We can reject the idea that 17% is

313
00:24:16,000 --> 00:24:20,000
some constant like e or one
over pi or something like that.

314
00:24:20,000 --> 00:24:25,000
But we look at these numbers,
and a lot of folks wanted to

315
00:24:25,000 --> 00:24:29,000
interpret these as physiological
numbers. Something about the

316
00:24:29,000 --> 00:24:38,000
biology of these
traits. So --

317
00:24:38,000 --> 00:24:42,000
-- we can give this thing a name,
the frequency of non-parental types.

318
00:24:42,000 --> 00:24:47,000
We can call this the Recombination
Rate. Because we've got new

319
00:24:47,000 --> 00:24:51,000
combinations, right? This
recombination rate might mean,

320
00:24:51,000 --> 00:24:56,000
and you know already that you're
thinking what it really means is --

321
00:24:56,000 --> 00:25:12,000
-- somehow
we have black,

322
00:25:12,000 --> 00:25:19,000
black, plus, plus. And in
the F1 we have vestigial,

323
00:25:19,000 --> 00:25:26,000
vestigial, plus, plus.
And that somehow these two

324
00:25:26,000 --> 00:25:33,000
chromosomes have exchanged genetic
material so that the new chromosome

325
00:25:33,000 --> 00:25:39,000
you get is like this. And
you get a recombinant type.

326
00:25:39,000 --> 00:25:45,000
You get recombination between
these chromosomes. And there's a

327
00:25:45,000 --> 00:25:51,000
recombination rate. And the
recombination rate is how

328
00:25:51,000 --> 00:25:57,000
often this kind of an exchange
occurs. And what does the

329
00:25:57,000 --> 00:26:02,000
recombination rate depend on? The
distance between those two genes.

330
00:26:02,000 --> 00:26:06,000
You know this because you've
been told this since kindergarten,

331
00:26:06,000 --> 00:26:10,000
right? It's in all the high
school textbooks and things like or

332
00:26:10,000 --> 00:26:15,000
whatever. They teach genetics
earlier and earlier these days and

333
00:26:15,000 --> 00:26:19,000
it's on TV and stuff. But
that's a nice idea that the

334
00:26:19,000 --> 00:26:24,000
recombination rate depends on
the distance. And this rate,

335
00:26:24,000 --> 00:26:28,000
which might be 17% or it might be 1%
or it might be 8% or it might be who

336
00:26:28,000 --> 00:26:33,000
knows, depends on the distances,
reflection of the distance.

337
00:26:33,000 --> 00:26:36,000
But, golly, what's the evidence
for that? Aren't we just making up a

338
00:26:36,000 --> 00:26:40,000
theory to explain the data here?
We don't have a theory to, we're

339
00:26:40,000 --> 00:26:44,000
just trying to fix the Chromosomal
Theory. The Chromosomal Theory

340
00:26:44,000 --> 00:26:47,000
wouldn't predict these recombinant
types. It would have predicted we

341
00:26:47,000 --> 00:26:51,000
only get parental types out. So
because we do get non-parental

342
00:26:51,000 --> 00:26:55,000
types out we say, well,
chromosomes are promiscuous

343
00:26:55,000 --> 00:26:59,000
and they'll exchange parts.
Because we don't always get the same

344
00:26:59,000 --> 00:27:03,000
ratio, we have to make up the fact
that somehow the ratio is different

345
00:27:03,000 --> 00:27:07,000
because of something,
distance. We cannot observe

346
00:27:07,000 --> 00:27:12,000
distance. No way that Morgan was
able to look at the chromosome and

347
00:27:12,000 --> 00:27:16,000
see where the genes were. So
basically any number you want to

348
00:27:16,000 --> 00:27:21,000
give him, he'll just say it's the
distance. This is not overwhelming.

349
00:27:21,000 --> 00:27:25,000
Now, what's even the evidence
that chromosomes exchange material?

350
00:27:25,000 --> 00:27:30,000
Why do we think stuff
like that even happens?

351
00:27:30,000 --> 00:27:34,000
Ah, it turns out you can take fruit
fly gametes, and other gametes,

352
00:27:34,000 --> 00:27:38,000
and look at them in the microscope.
What you do is to look at them

353
00:27:38,000 --> 00:27:43,000
closely, the chromosomes during
meiosis. You put a cover slip on

354
00:27:43,000 --> 00:27:47,000
them, you squish them down,
add a little dye and you look.

355
00:27:47,000 --> 00:27:52,000
And it turns out that really truly,
when you look in the microscope, you

356
00:27:52,000 --> 00:27:56,000
can see stuff like that, of
chromosomes lying on top of each

357
00:27:56,000 --> 00:28:01,000
other like that. These
are called chiasmata,

358
00:28:01,000 --> 00:28:05,000
crosses. Chiasma or the plural
chiasmata. You can see it in the

359
00:28:05,000 --> 00:28:09,000
microscope. So does that
convincingly demonstrate that

360
00:28:09,000 --> 00:28:13,000
recombination occurs? Are
you overwhelmed? Why not?

361
00:28:13,000 --> 00:28:18,000
Yeah. You put a bunch
of chromosomes down,

362
00:28:18,000 --> 00:28:22,000
you put a glass cover slip and
squish them. The fact that two

363
00:28:22,000 --> 00:28:26,000
things lie on top of each other,
I mean this is what it takes to do

364
00:28:26,000 --> 00:28:30,000
science. Is you actually
have to be pretty

365
00:28:30,000 --> 00:28:33,000
hardnosed about not being willing
to take evidence that supports your

366
00:28:33,000 --> 00:28:36,000
theory just because it supports
your theory. Skepticism is pretty

367
00:28:36,000 --> 00:28:40,000
important here. So you
squish down the cover slip

368
00:28:40,000 --> 00:28:43,000
and sometimes, not
always, sometimes some

369
00:28:43,000 --> 00:28:46,000
chromosome lands on top
of some other chromosome.

370
00:28:46,000 --> 00:28:49,000
Big deal. So how are we going
to actually get any convincing

371
00:28:49,000 --> 00:28:52,000
predictions? That's what it
took with Mendel. What convincing

372
00:28:52,000 --> 00:28:55,000
predictions can we make that
this recombination phenomenon has

373
00:28:55,000 --> 00:28:59,000
something to do with the disposition
of genes along chromosomes?

374
00:28:59,000 --> 00:29:04,000
And, if so, might provide some
support for the Chromosomal Theory

375
00:29:04,000 --> 00:29:09,000
of Inheritance? Well,
when you're in a quandary,

376
00:29:09,000 --> 00:29:14,000
you've got some new area, you've got
messy data, you need new thinking.

377
00:29:14,000 --> 00:29:19,000
Where do you get new thinking from?
You get new thinking from students

378
00:29:19,000 --> 00:29:24,000
because old folks are thinking,
you know, in whatever way they were

379
00:29:24,000 --> 00:29:29,000
thinking. So what you really need
are young students to come along

380
00:29:29,000 --> 00:29:34,000
into the field and look at
the data in some fresh way.

381
00:29:34,000 --> 00:29:39,000
So, in this case, the
hero was a UROP student at

382
00:29:39,000 --> 00:29:44,000
Columbia. They didn't call it UROP,
but it was the same thing. He was a

383
00:29:44,000 --> 00:29:49,000
sophomore working in the lab of
Thomas Hunt Morgan who came along

384
00:29:49,000 --> 00:29:54,000
and solved this problem very nicely.
You know, I think in part because

385
00:29:54,000 --> 00:30:00,000
sophomores had not been polluted
by all sorts of prior thinking.

386
00:30:00,000 --> 00:30:05,000
So the idea of genetic maps
arises through the work of one

387
00:30:05,000 --> 00:30:10,000
Alfred Sturtevant.
Sturtevant was a sophomore at

388
00:30:10,000 --> 00:30:14,000
Columbia in 1911. And while
an undergraduate working

389
00:30:14,000 --> 00:30:18,000
in the lab of Thomas Hunt Morgan,
he went home, you know, he was

390
00:30:18,000 --> 00:30:22,000
working in the lab, and he
took home a pile of data.

391
00:30:22,000 --> 00:30:26,000
And he said I've got to make
sense out of all this data.

392
00:30:26,000 --> 00:30:30,000
I don't understand
exactly what's going on.

393
00:30:30,000 --> 00:30:34,000
Here's some of the data he took
home. Morgan's lab had set up crosses,

394
00:30:34,000 --> 00:30:39,000
not just involving two traits
but three traits simultaneously.

395
00:30:39,000 --> 00:30:43,000
They actually set up crosses
involving three traits,

396
00:30:43,000 --> 00:30:48,000
black, what's called cinnabar
which is an eye color,

397
00:30:48,000 --> 00:30:52,000
and vestigial. And they looked at
the F1 when crossing back to the

398
00:30:52,000 --> 00:30:57,000
triply homozygous fly here,
and they counted the number of

399
00:30:57,000 --> 00:31:02,000
recombinant types
of different sorts.

400
00:31:02,000 --> 00:31:05,000
You could look at recombinant
types between black and vestigial.

401
00:31:05,000 --> 00:31:08,000
We've already got that data. You
could look at recombinant types

402
00:31:08,000 --> 00:31:11,000
between black and cinnabar. You
could look at recombinant types

403
00:31:11,000 --> 00:31:14,000
between cinnabar and vestigial.
Now, I've drawn this as if these

404
00:31:14,000 --> 00:31:17,000
live on a chromosome and I know
their order. You've got to remember,

405
00:31:17,000 --> 00:31:20,000
we don't know that they live
on a chromosome. And Sturtevant

406
00:31:20,000 --> 00:31:23,000
certainly didn't know their order.
OK? But I have to draw it for you,

407
00:31:23,000 --> 00:31:26,000
so I'm drawing it for you because
the notation he would have used was

408
00:31:26,000 --> 00:31:30,000
much too messy and there's
no point in learning it.

409
00:31:30,000 --> 00:31:36,000
So he begins to look at the data
from these different crosses.

410
00:31:36,000 --> 00:31:42,000
What he finds is when he looks
only at black and vestigial,

411
00:31:42,000 --> 00:31:49,000
so he ignores what happened with
cinnabar, what's the recombination

412
00:31:49,000 --> 00:31:55,000
rate, the frequency with
which he observes new types,

413
00:31:55,000 --> 00:32:01,000
non-parental types? Well,
they had already done the

414
00:32:01,000 --> 00:32:05,000
experiment in the lab.
And what's the answer?

415
00:32:05,000 --> 00:32:09,000
17%. Now, he then looks at
black to cinnabar. So he just,

416
00:32:09,000 --> 00:32:13,000
you know, covers up the genotype
of vestigial. There are four

417
00:32:13,000 --> 00:32:18,000
possibilities,
black, cinnabar,

418
00:32:18,000 --> 00:32:22,000
black, plus, plus,
cinnabar, black, cinnabar.

419
00:32:22,000 --> 00:32:26,000
He looks at the parental types,
black, cinnabar or plus, plus. He

420
00:32:26,000 --> 00:32:30,000
looks at the non-parental types,
the recombinant types, plus,

421
00:32:30,000 --> 00:32:34,000
cinnabar or black, plus.
He counts up the number of

422
00:32:34,000 --> 00:32:36,000
non-parental types to the total
number of flies and he gets a

423
00:32:36,000 --> 00:32:39,000
recombination rate of 9%. OK?
So I'm just going to draw you

424
00:32:39,000 --> 00:32:41,000
this. He took out a piece of
paper and he drew himself black,

425
00:32:41,000 --> 00:32:44,000
cinnabar, vestigial. He said I
believe this has something to do

426
00:32:44,000 --> 00:32:47,000
with distance. This was
17%. The probability of a

427
00:32:47,000 --> 00:32:49,000
crossover occurring, of a
recombination occurring between

428
00:32:49,000 --> 00:32:52,000
black and vestigial 17%. And
the probability of a crossover

429
00:32:52,000 --> 00:32:54,000
occurring, the frequency of a
crossover occurring between black

430
00:32:54,000 --> 00:32:57,000
and cinnabar was 9%. Got
any prediction? Cinnabar,

431
00:32:57,000 --> 00:33:00,000
vestigial should be
about 8%, give or take.

432
00:33:00,000 --> 00:33:09,000
But what if his picture is wrong.
What's another picture that might

433
00:33:09,000 --> 00:33:19,000
be were cinnabar is? Oh,
yeah. There's an alternative

434
00:33:19,000 --> 00:33:29,000
picture, isn't there? The
alternative picture is black,

435
00:33:29,000 --> 00:33:39,000
vestigial, cinnabar over here at
9%, 17%. In which case, what's the

436
00:33:39,000 --> 00:33:49,000
prediction for cinnabar,
vestigial? 26%, give or take,

437
00:33:49,000 --> 00:33:59,000
right? We've got to be a
little rough about these things.

438
00:33:59,000 --> 00:34:04,000
Well, that's not a single prediction,
but it's down to two alternatives.

439
00:34:04,000 --> 00:34:09,000
He's either expecting about
8% or he's expecting about 26%.

440
00:34:09,000 --> 00:34:25,000
So two alternative predictions.

441
00:34:25,000 --> 00:34:32,000
Cinnabar, vestigial combination
rate 8%. Mm, that's good.

442
00:34:32,000 --> 00:34:39,000
That's very good. The first
time anybody's made a prediction,

443
00:34:39,000 --> 00:34:46,000
and a quantitative prediction
that's just gotten verified by data.

444
00:34:46,000 --> 00:34:53,000
Sturtevant also does one
other interesting thing.

445
00:34:53,000 --> 00:35:00,000
He looks at a fourth thing,
which is a little bit interesting.

446
00:35:00,000 --> 00:35:04,000
When I look at the types of
gametes that can come out of her,

447
00:35:04,000 --> 00:35:08,000
right? If this idea of genetic
recombination is correct,

448
00:35:08,000 --> 00:35:13,000
that sometimes in this F1 parent
a crossover has occurred here,

449
00:35:13,000 --> 00:35:17,000
sometimes a crossover has occurred
here, and the crossover here would

450
00:35:17,000 --> 00:35:22,000
give rise to black, plus,
plus or plus, cinnabar,

451
00:35:22,000 --> 00:35:26,000
vestigial. Here it would
give rise to black, cinnabar,

452
00:35:26,000 --> 00:35:31,000
plus or plus, plus, vestigial
if it went the other way.

453
00:35:31,000 --> 00:35:37,000
Is it possible that occasionally,
under this model, you might get two

454
00:35:37,000 --> 00:35:43,000
crossovers? Might it be the case,
if we believe in this stuff, that a

455
00:35:43,000 --> 00:35:50,000
crossover might occur between black
and cinnabar and a crossover might

456
00:35:50,000 --> 00:35:56,000
occur between vestigial and cinnabar?
Could be. How often do you think

457
00:35:56,000 --> 00:36:02,000
that would happen?
Sorry? Rarely.

458
00:36:02,000 --> 00:36:06,000
How rarely? What's the
chance of a crossover here?

459
00:36:06,000 --> 00:36:10,000
About 9%, right?
A crossover here?

460
00:36:10,000 --> 00:36:14,000
About 8%. Let's say 9%, 8% or
about 10% just for roundness.

461
00:36:14,000 --> 00:36:19,000
There's about a 10% chance of a
crossover in the first interval.

462
00:36:19,000 --> 00:36:23,000
It's about a 10% chance of a
crossover in the second interval.

463
00:36:23,000 --> 00:36:27,000
It's about 1% of the time.
Much lower than the others.

464
00:36:27,000 --> 00:36:31,000
But about 1% of the time you
might see what kind of chromosomes

465
00:36:31,000 --> 00:36:37,000
emerging? Black
plus, vestigial.

466
00:36:37,000 --> 00:36:43,000
So black plus, vestigial or
plus, cinnabar, vestigial. These

467
00:36:43,000 --> 00:36:49,000
chromosomes, oops, plus.
Thank you. These would be

468
00:36:49,000 --> 00:36:55,000
doubly recombinant chromosomes.
They would need two recombination

469
00:36:55,000 --> 00:37:01,000
events to explain them. And
you even have a prediction that

470
00:37:01,000 --> 00:37:05,000
you might see them at
about 1%. And, sure enough,

471
00:37:05,000 --> 00:37:09,000
Sturtevant sees them. It's
actually somewhat less than 1%.

472
00:37:09,000 --> 00:37:12,000
It turns out that double is
a little less likely than the

473
00:37:12,000 --> 00:37:15,000
independent. There's a little
bit of what's called interference,

474
00:37:15,000 --> 00:37:19,000
but don't worry about it.
That's a second order effect.

475
00:37:19,000 --> 00:37:22,000
At a frequency of about 1%
he sees double recombinants.

476
00:37:22,000 --> 00:37:26,000
That tells him who is in the middle.
If cinnabar is the one that has

477
00:37:26,000 --> 00:37:29,000
this property, because
if he asked how often does

478
00:37:29,000 --> 00:37:33,000
cinnabar get inherited together
with plus, plus that's very rare.

479
00:37:33,000 --> 00:37:38,000
But vestigial gets inherited
with plus, plus 9% of the time,

480
00:37:38,000 --> 00:37:44,000
black gets inherited with plus,
plus, sorry, 8% or 9% of the time,

481
00:37:44,000 --> 00:37:50,000
but cinnabar is pretty rare. So all
this together says that this model

482
00:37:50,000 --> 00:37:56,000
here of a linear chromosome is now
making some pretty good quantitative

483
00:37:56,000 --> 00:38:01,000
predictions about what's going on.
But of course this is just three

484
00:38:01,000 --> 00:38:05,000
different genes, black,
cinnabar and vestigial.

485
00:38:05,000 --> 00:38:09,000
What would you like?
More of them at least. Me,

486
00:38:09,000 --> 00:38:13,000
personally, I go for all.
I'm with you. But he's an

487
00:38:13,000 --> 00:38:17,000
undergraduate and he's
got what he can. So more.

488
00:38:17,000 --> 00:38:21,000
Well, it turns out that of course
Morgan's lab was busily making

489
00:38:21,000 --> 00:38:25,000
crosses and all this kind of stuff
and there was more data available.

490
00:38:25,000 --> 00:38:29,000
So when he saw this happening
he said, all right, let's look

491
00:38:29,000 --> 00:38:34,000
at some more things. And he
began, because there was so

492
00:38:34,000 --> 00:38:38,000
much data from the lab, going
around and taking all this

493
00:38:38,000 --> 00:38:43,000
stuff, lobe and curved wing
and other kinds of funny traits,

494
00:38:43,000 --> 00:38:47,000
and he began looking at frequencies.
And he found this was about 9%.

495
00:38:47,000 --> 00:38:52,000
And this was about 8%. And
he found this was about 5%.

496
00:38:52,000 --> 00:38:56,000
And he found that this was about
5%. And if these two were 5%

497
00:38:56,000 --> 00:39:01,000
his prediction was 10%. And his
prediction here would be 13%,

498
00:39:01,000 --> 00:39:06,000
etc. And it all pretty closely
checked out. This was highly

499
00:39:06,000 --> 00:39:11,000
constrained, the idea that the
recombination rates would fit a

500
00:39:11,000 --> 00:39:17,000
simple linear model. It's
not perfect, of course,

501
00:39:17,000 --> 00:39:22,000
because imagine what
happens. Suppose I have 10%,

502
00:39:22,000 --> 00:39:27,000
10%, 10%, 10%, 10% and I have
ten loci, you know, I have

503
00:39:27,000 --> 00:39:31,000
ten such intervals. What will
the recombination rate be?

504
00:39:31,000 --> 00:39:35,000
100%. And then if have five
more? 150%. What does that mean?

505
00:39:35,000 --> 00:39:38,000
So clearly something is wrong
about just using percents.

506
00:39:38,000 --> 00:39:42,000
You have to kind of, I
mean for the aficionados,

507
00:39:42,000 --> 00:39:45,000
really the percent reflects
the number of crossovers.

508
00:39:45,000 --> 00:39:49,000
But obviously you have to do a
little bit of correction because you

509
00:39:49,000 --> 00:39:52,000
cannot have, you know, if I
keep piling on the intervals

510
00:39:52,000 --> 00:39:56,000
double crossovers will happen which
won't produce recombinant types.

511
00:39:56,000 --> 00:40:00,000
But don't worry about it. We can
just add percentages for today.

512
00:40:00,000 --> 00:40:04,000
And when you do all this it works.
Sturtevant did this all in one

513
00:40:04,000 --> 00:40:08,000
evening. In his autobiography that
he wrote about 50 years later he

514
00:40:08,000 --> 00:40:12,000
says I went home one evening,
blew off all of my homework, and

515
00:40:12,000 --> 00:40:17,000
stayed up all night and was able
to make sense out of all this data.

516
00:40:17,000 --> 00:40:21,000
So I think this is an example
of a productive all-nighter.

517
00:40:21,000 --> 00:40:25,000
[LAUGHTER] And also this is an
example of when it's the right

518
00:40:25,000 --> 00:40:29,000
choice to blow off your homework.
If anyone wishes to do things like

519
00:40:29,000 --> 00:40:33,000
this and be as productive,
you're certainly entitled to blow

520
00:40:33,000 --> 00:40:36,000
off the homework here, too.
But do bring in good data like

521
00:40:36,000 --> 00:40:40,000
this when you're done. Anyway,
this notion is a genetic

522
00:40:40,000 --> 00:40:44,000
map. A genetic map was a
totally abstract concept,

523
00:40:44,000 --> 00:40:47,000
much like Mendel's abstract
concept that there were even genes.

524
00:40:47,000 --> 00:40:51,000
Now we're going further and
we're saying whatever genes are,

525
00:40:51,000 --> 00:40:54,000
we still don't know that they're DNA,
etc. Whatever they are they live on

526
00:40:54,000 --> 00:40:58,000
a line, and they behave
as if they live on a line,

527
00:40:58,000 --> 00:41:02,000
and they undergo
recombinations, etc.

528
00:41:02,000 --> 00:41:05,000
And when I see a recombination
rate, a recombination frequency, a

529
00:41:05,000 --> 00:41:09,000
recombination rate that's zero,
it must mean the genes are very

530
00:41:09,000 --> 00:41:13,000
close together. If I see
a recombination rate very,

531
00:41:13,000 --> 00:41:17,000
very close, never recombine,
recombination rates,

532
00:41:17,000 --> 00:41:21,000
oh, I don't know, maybe
10% or something, well,

533
00:41:21,000 --> 00:41:25,000
there's some distance between them.
And if they're further and further

534
00:41:25,000 --> 00:41:29,000
and further away, or on
totally different chromosomes,

535
00:41:29,000 --> 00:41:33,000
what would be the recombination rate
here for two different chromosomes?

536
00:41:33,000 --> 00:41:37,000
A half. Half of these
are non-parental types.

537
00:41:37,000 --> 00:41:42,000
So when I get up to a recombination
rate of 50% then it means that they

538
00:41:42,000 --> 00:41:46,000
live on, that they are
so-called unlinked to each other.

539
00:41:46,000 --> 00:41:51,000
Either they are on different
chromosomes entirely or I suppose

540
00:41:51,000 --> 00:41:56,000
it's possible, and in
fact it is possible that

541
00:41:56,000 --> 00:42:00,000
they're so far away on the same
chromosome that the probability of

542
00:42:00,000 --> 00:42:05,000
crossovers occurring is so high
that they are de-correlated from each

543
00:42:05,000 --> 00:42:10,000
other and I cannot observe any
recombination rate less than 50%,

544
00:42:10,000 --> 00:42:13,000
It turns out many chromosomes
are sufficiently big that lots of

545
00:42:13,000 --> 00:42:16,000
crossovers can occur and you cannot
actually detect linkage at the two

546
00:42:16,000 --> 00:42:19,000
ends of the chromosome. But
if you string together some

547
00:42:19,000 --> 00:42:23,000
genes in between you can see that
this is linked to this is linked to

548
00:42:23,000 --> 00:42:26,000
this is linked to this is
linked to this is linked to this.

549
00:42:26,000 --> 00:42:30,000
OK? All right. Good. So
Sturtevant is another one of my

550
00:42:30,000 --> 00:42:35,000
heroes because he comes up with
this utterly abstract model here of

551
00:42:35,000 --> 00:42:40,000
chromosomes, of genetic maps.
All right. I meant to get that

552
00:42:40,000 --> 00:42:45,000
board. Does someone have a call?
OK. So last of all let me take

553
00:42:45,000 --> 00:42:50,000
Section 4 here. This
begins to provide fairly

554
00:42:50,000 --> 00:42:55,000
convincing evidence for the
Chromosomal Theory because it made a

555
00:42:55,000 --> 00:43:00,000
whole lot of pretty
whacky predictions.

556
00:43:00,000 --> 00:43:05,000
And they pretty much hold up.
Here's another thing that provided

557
00:43:05,000 --> 00:43:10,000
a lot of good evidence for
it, and that was sex linkage.

558
00:43:10,000 --> 00:43:16,000
Also in
Morgan's lab,

559
00:43:16,000 --> 00:43:21,000
which was a very productive place,
I must say, folks were wondering

560
00:43:21,000 --> 00:43:27,000
about the fact that chromosomes,
although they almost always occurred

561
00:43:27,000 --> 00:43:32,000
in pairs that lined up
with each other perfectly,

562
00:43:32,000 --> 00:43:38,000
in many species there
was one odd couple.

563
00:43:38,000 --> 00:43:44,000
A pair of chromosomes that always
paired up with each other but they

564
00:43:44,000 --> 00:43:50,000
didn't look the same.
This one looks like an X.

565
00:43:50,000 --> 00:43:56,000
This one kind of had the shape of a
Y. And hence they got the names the

566
00:43:56,000 --> 00:44:02,000
X and the Y chromosomes.
Now here was something very

567
00:44:02,000 --> 00:44:06,000
interesting. In fruit flies it was
always the males that had an XY pair.

568
00:44:06,000 --> 00:44:11,000
In females it was always an XX pair.
What does that tell us about these

569
00:44:11,000 --> 00:44:15,000
chromosomes and what they do?
Sorry? Determines gender. Wait a

570
00:44:15,000 --> 00:44:19,000
minute. Why do you believe
it determines gender?

571
00:44:19,000 --> 00:44:24,000
It just correlated with gender.
Females have these two funny

572
00:44:24,000 --> 00:44:28,000
chromosomes. Males have, I'm
sorry. Females have these two

573
00:44:28,000 --> 00:44:32,000
Xs. Males have
an X and Y.

574
00:44:32,000 --> 00:44:36,000
Does it have to mean that
they determine gender?

575
00:44:36,000 --> 00:44:40,000
Maybe gender determines them.
Maybe what happens is that in

576
00:44:40,000 --> 00:44:43,000
female cells you get both
chromosomes, but in male cells some

577
00:44:43,000 --> 00:44:47,000
enzyme comes along and chews
off the end of the chromosome.

578
00:44:47,000 --> 00:44:50,000
No, no, really. Maybe this is
some physiological state of the

579
00:44:50,000 --> 00:44:54,000
chromosomes. Why are you so ready
to leap to the conclusion that the

580
00:44:54,000 --> 00:44:58,000
chromosomes determine sex,
rather the gender, than the gender

581
00:44:58,000 --> 00:45:02,000
determines the chromosomes?
It's because you know the answer,

582
00:45:02,000 --> 00:45:06,000
you've been told all this, etc. But
I, again, invite you to take apart

583
00:45:06,000 --> 00:45:10,000
what support you have for that
and ask how would you know,

584
00:45:10,000 --> 00:45:14,000
right? All of these things you
get told, but how would you know?

585
00:45:14,000 --> 00:45:18,000
And there was great argument
about was this really the case?

586
00:45:18,000 --> 00:45:22,000
So how could you convince
people that this was true?

587
00:45:22,000 --> 00:45:27,000
It's not obvious to know
which way it would go.

588
00:45:27,000 --> 00:45:32,000
The most convincing evidence, not
the only evidence, but the most

589
00:45:32,000 --> 00:45:37,000
convincing evidence came from a
single fly that had been isolated in

590
00:45:37,000 --> 00:45:43,000
Morgan's lab. And F0 fly that had
the very interesting property that

591
00:45:43,000 --> 00:45:48,000
instead of the normal red drosophila
eyes this fly had white eyes.

592
00:45:48,000 --> 00:45:54,000
Whereas, this was the normal
fly with red eyes. And we'll

593
00:45:54,000 --> 00:45:58,000
use a female here. When
you cross together the white

594
00:45:58,000 --> 00:46:01,000
eyed fly and the red eyed fly,
what you find is that in the F1

595
00:46:01,000 --> 00:46:05,000
generation all the flies, males
and females, are normal red

596
00:46:05,000 --> 00:46:12,000
eyes.

597
00:46:12,000 --> 00:46:20,000
When I take, however, a normal
female and I cross her back,

598
00:46:20,000 --> 00:46:28,000
sorry. A normal female emerging
from this F1 generation,

599
00:46:28,000 --> 00:46:36,000
and now I cross her to a normal
male, here's what happens.

600
00:46:36,000 --> 00:46:50,000
All of her daughters are normal,
but her sons, half are normal and

601
00:46:50,000 --> 00:47:07,000
half are
white-eyed again.

602
00:47:07,000 --> 00:47:13,000
That's weird. For the first
time we have a genetic trait,

603
00:47:13,000 --> 00:47:19,000
eye color, that is showing
correlation in its inheritance with

604
00:47:19,000 --> 00:47:25,000
sex. So that says for the first
time we're beginning to see

605
00:47:25,000 --> 00:47:31,000
something that looks like linkage,
like genetic correlation, genetic

606
00:47:31,000 --> 00:47:38,000
nearness, like genetic mapping
that would relate eye color to sex.

607
00:47:38,000 --> 00:47:42,000
What's the model? Well,
of course the model here is

608
00:47:42,000 --> 00:47:47,000
that this fly, we
know the answer,

609
00:47:47,000 --> 00:47:52,000
is X over Y, it's a male. And
the X chromosome here has a

610
00:47:52,000 --> 00:47:57,000
mutation that makes it white-eyed.
What's this normal fly over here?

611
00:47:57,000 --> 00:48:02,000
X over X. And its X
chromosomes are normal.

612
00:48:02,000 --> 00:48:07,000
When we go to the next generation,
what kind of offspring are there?

613
00:48:07,000 --> 00:48:13,000
The daughters of this cross,
what's their genotype? What did

614
00:48:13,000 --> 00:48:18,000
they get from dad? They
always get a normal X

615
00:48:18,000 --> 00:48:23,000
chromosome from dad. I'm
sorry, from mom I mean.

616
00:48:23,000 --> 00:48:29,000
What did they get from dad, these
daughters? They always got the X

617
00:48:29,000 --> 00:48:34,000
with the white eye. Why
didn't they get the Y?

618
00:48:34,000 --> 00:48:40,000
Because they're daughters,
right? If they got the Y they'd be

619
00:48:40,000 --> 00:48:45,000
sons. But they're daughters. So
the daughters always are getting

620
00:48:45,000 --> 00:48:50,000
this chromosome. Now, when
you mate these back to a

621
00:48:50,000 --> 00:48:56,000
normal male, X over Y, the
daughters are of what type?

622
00:48:56,000 --> 00:49:01,000
What did they get from
their dad? Always an X plus.

623
00:49:01,000 --> 00:49:06,000
And what did they get from their
mom? Either an X with a mutation or

624
00:49:06,000 --> 00:49:11,000
an X plus. Either way they're
normal, because we're assuming that

625
00:49:11,000 --> 00:49:16,000
this white-eyed mutation is
recessive. What did the sons get?

626
00:49:16,000 --> 00:49:21,000
What did they get from their
dad? Y. Why don't they get the X?

627
00:49:21,000 --> 00:49:27,000
Because they're sons. What
did they get from their mom?

628
00:49:27,000 --> 00:49:31,000
Half of them get the X plus,
half of them get the X mutant,

629
00:49:31,000 --> 00:49:35,000
and that explains cleanly
what's going on. Now,

630
00:49:35,000 --> 00:49:39,000
the Y chromosome, being
a short stubby little

631
00:49:39,000 --> 00:49:43,000
chromosome, doesn't have a copy
of this gene for eye color at all.

632
00:49:43,000 --> 00:49:47,000
So you might as well regard
it as being, you know,

633
00:49:47,000 --> 00:49:51,000
recessive, as carrying the
allele for the recessive trait.

634
00:49:51,000 --> 00:49:55,000
It doesn't have any functional
copy. So for a male he only

635
00:49:55,000 --> 00:50:00,000
gets a copy from mom. And
what he got from mom completely

636
00:50:00,000 --> 00:50:05,000
determines his phenotype. Thus,
the transmission of eye color,

637
00:50:05,000 --> 00:50:09,000
a trait controlled by a gene on
the X chromosome correlated so

638
00:50:09,000 --> 00:50:14,000
beautifully with the
transmission of the trait sex.

639
00:50:14,000 --> 00:50:19,000
That provided a convincing
argument that it was the chromosomes

640
00:50:19,000 --> 00:50:24,000
controlling sex rather than
the sex controlling chromosomes.

641
00:50:24,000 --> 00:50:29,000
All right. So you know all this
stuff. You've all heard of Mendel.

642
00:50:29,000 --> 00:50:32,000
You've all heard of recombination.
You've heard of, I suppose, genetic

643
00:50:32,000 --> 00:50:36,000
maps. You know about X and Y
chromosomes and things like that.

644
00:50:36,000 --> 00:50:40,000
What I want you to take away from
all of this is that in order to

645
00:50:40,000 --> 00:50:44,000
really know things you have
to struggle against models.

646
00:50:44,000 --> 00:50:48,000
You have to understand whether
the model is just being made up to

647
00:50:48,000 --> 00:50:52,000
explain the data or whether the
model has been proved by testing it

648
00:50:52,000 --> 00:50:56,000
in any serious kinds of ways.
All this stuff took 30 or 40 years

649
00:50:56,000 --> 00:51:00,000
of serious battle before the last
people caved in and said this is all

650
00:51:00,000 --> 00:51:05,000
proven. Of course, going
forward we'll assume it's all

651
00:51:05,000 --> 00:51:10,000
proven and you know what to do
with it. And onward to next time.