So in this last lecture, what I'd like to do is I'd like to
now begin to talk about genetics. And when we talked early on in the
semester I was showing you this way that you can study biological
function. Biochemists, for the most part, study how
proteins work. And what genetics does,
steadying function, it's enable one to discover genes.
And the molecular biology that we're going to be talking about in the
back part of the course has been really totally amazing because it's
allowed one to go back and forth between genes and proteins,
something that used to be very, very hard until recombinant DNA came
into the picture. Now, up until now I've sort of
mentioned genetics as we went along.
But we haven't really talked about it as a discipline and the kind of
power that this experimental approach has. Thank you.
I could have done this without notes but it's easier to have them.
I just have my little help here. So I know some of you have written
in your comments I didn't think there was going to be
so much chemistry. Well, we had a little bit of a bout
with chemistry. And then some of you found that we
were going away from bonds and thinking about 3-dimensionality,
and that was another kind of thinking. And then sort of trying
to work through the genetic code is almost another.
And I think you'll find here, as we start to go through genetics
that you have to stretch your brain in another direction.
And part of one of the really interesting things about biology
today is you cannot just sort of think about it in one kind of very
comfortable way of thinking and really take advantage of everything
that's out there. You need to be able to talk in
multiple languages and multiple disciplines. And so today I want to
just kind of briefly give you an introductory sense of how genetics,
that I hope will give you, let you see the power of it by very,
very simple techniques. And remember what you're doing here is
you're studying variants of the living organism.
So if you see something that's wrong with it you know it's
important, but you know the rest of the job is to figure out what's
wrong. And I've sort of given you and used some examples.
When we talked about the streptococcus with the smooth
colonies, I talked about how people had noticed rough colonies.
Well, those sorts of things had been a change in the DNA and they
weren't making these polysaccharide capsules anymore.
Or when I talked to you about the mutant bacteria that had lost
mismatch repair, they had a high mutation frequency
compared to a wild type. So up until now I've sort of
mentioned them, but we haven't really talked about
how one goes about studying things in a systematic genetic way.
So let me begin with just a few definitions. I realize this is a
little dry but we need to make sure that we're all on the same page in
terms of the language. So a mutant is a variant of a
normal organism.
It has a change in its DNA and the kinds of mutants can vary all over
the map. For example, if we had an E. coli that was,
we might call it penn-resistant, that could mean it was resistant to
penicillin and would grow in the presence of the antibiotics.
Whereas, ordinary ones would die. Or if we had what we call a
his-minus mutant broken in the biosynthesis of histidine
won't grow --
-- unless you add histidine to the medium. Those are a couple of
simple examples. When we start right after lecturing,
when I come back, I'm going to begin with Mendel,
which is the more classic and usual way of teaching genetics.
And he used various traits of peas. Yellow and green seeds and wrinkled
and round. And you can see what he was working with there.
Another favorite organism for genetic study has been the fruit fly
or drosophila. You can even see that they have red
eyes. If you take a close look next time if one lands on your sandwich
or your drink or something in the summer. But you can see,
for example, people were able to get white mutants that have white eyes.
There's something broken in making the pigment that's going to make it
red. Here's an even weirder one. This is a single mutation in
drosophila. It affects a developmental process instead of
something else. And what happens is this is a
drosophila head. And normally there are antennae
that grow out of the top of the head. And you can see what's happened in
this mutant is there's a pair of legs growing out of the top of the
head. It's just a single gene that's been changed,
but it's a gene that plays a role in the developmental program,
the patterning that makes certain cells become specialized to become
certain other things. So it's just to give you an idea.
And I showed you these. We've talked about the xeroderma
pigmentosum, one change. A person with this has got a gene
that's broken in dealing with damage from UV. Or I've given you an
example of what they call Werner syndrome where a change in a single
gene, it's actually a kind of gene whose proteins are involved in
unwinding DNA, of all things, can give you this
premature aging phenotype where the woman looks normal at 16 but older
at the age of 48. So all of these are,
if you will, mutants that are a variant of a wild type.
And then this is something people often get confused between these two
terms. The mutation is the actual change in the DNA.
Now, one other thing that's sort of implicit in this definition is that
we know what a normal organism is. Well, if you look around this room,
what's a normal human? Well, I'm OK but I don't know about the rest of
you. I'm sure we all feel that way, but we have a lot of variation in it.
So, to some extent, it's an operational definition.
And most often it's applied, if you're studying something like
drosophila or E. coli, someone has been propagating a
particular bacterial isolate in the lab for a long time.
And you call that one the wild type, even though, in fact, in the case of
an E. coli, it may have changed a bit so it likes to grow in the
conditions that it finds in the lab. But this sort of normal is an
operational definition. Now, another important term that
geneticists use all the time is the phenotype. The word phenotype.
And that's the ensemble --
-- of observable characteristics --
-- of an organism.
For example, in these resistance to
penicillin would be an example of a phenotype. A mutant that had
acquired the resistance would have the phenotype of being resistant.
Sometimes these phenotypes can be a little subtle.
A conditional phenotype would be a phenotype that you could observe
under one characteristic and not in another.
For example, a temperature sensitive phenotype --
Whatever it might be.
For example, it could be wild type at let's say 30 degrees but mutant
at 37 degrees centigrade. That may sound like a sort of
fiddly little thing. Why am I telling you about a
conditional phenotype right off? Well, suppose you wanted to study a
DNA polymerase. be it E. coli or me,
and it's the one that replicates your DNA? If we get a mutant that
just kills, knocks out the activity of the gene we have no living
organism to study, we cannot do any genetics.
But you can work around that. You can do genetics with essential
functions if you get a mutant where you see the mutant phenotypes,
let's say, at the high temperature but not at a low temperature.
And what that kind of thing usually comes from is a change in the
protein where the protein has one amino acid changed to something else
and it folds up, and at the lower temperature it's
able to fold up and do its thing. But it's not quite as stable as the
original protein. And if you raise the temperature it
unfolds a bit, and once it unfolds it doesn't work
or it gets degraded or something like that. OK.
So that's phenotype. The genotype then refers to the
state of the organism's genetic material with respect to whether its
wild type differs from it. So let me just put that down.
So this refers to the state --
-- of the organism's
genetic material --
-- with respect to whether it's wild type or it's mutant.
There's a key distinction, even though they sort of sound the
same. This is what you can see if you look at it but this is what's
actually changed. The genotype is what's actually
changed in the DNA. And there's a caution.
If it's something like a bacterium it's fine because it's only got one
copy of every gene. If I knock out a gene for making
histidine it cannot make histidine. The genotype and the phenotype are
the same. But if you have a diploid organism, which is the kind of
organism that we are and peas are and fruit flies are,
there are two copies of most genes, one from mom and one from dad.
And the only exceptions are the ones involved with the sex chromosomes.
Then you can get to something else, a more complicated situation.
Because let's say we have a usual thing where both copies of the gene
are plus, then the phenotype is wild type, but if we were to break one of
those copies by a mutation this one is still wild type.
The phenotype is still its wild type. You cannot tell from looking at it
that this one is different than that one. And one of the really
brilliant insights that Mendel had when he was looking at peas was he
would take things that were wrinkled and round and crossed them and he'd
see mixtures of things. And he realized some of those things
in there weren't the same as either the parents but they resembled one
of the parents. And I'll take you through that in
the next thing. So it's just a caution at the
moment that you have to be careful that phenotype and genotype are not
always the same. And then I've used the word gene.
That's the discrete unit --
-- of genetic information. We talked the other day about the
lacZ gene that encodes beta-galactosidase.
OK. So I think what I'd like to do, if I tell you,
for example, we made a lot of mutants of E. coli that were broken
by the biosynthesis of histidine and gave them to you,
if you were a good biochemist you might be able to work out how they
differed by studying them biochemically.
And let me just sort of give you a sense of how that would work so you
can see histidine or any of these amino acids. They're sort of
complicated and they have to be built up by a sequence of
biochemical steps with one enzyme catalyzing each step in the pathway.
And when people started out trying to study that kind of thing they
didn't know how it was made. All they knew was what the end
product was. And furthermore it was more of a
biosynthetic challenge even then trying to work out the steps of
glycolysis because actually quite a reasonable proportion of the protein
in any cell is devoted towards making energy.
So, relatively speaking, there's a fair amount of the protein.
Each of those proteins that are enzymes that we learned about,
for example, in glycolysis in a cell, if you crack a cell open they're
made in larger quantities. However, all the biosynthetic
enzymes, the things for making amino acids, for making purines,
pyrimidines, nucleotides or vitamins, which are only needed tiny amounts,
there are only little tiny bits of those enzymes.
So trying to work out the biosynthetic pathways for how those
things were made was much more difficult. And it was helped by
genetics in the following way. I'm not going to go into any great
detail, but if you imagine that there's a pathway for making
histidine. We don't know what it is.
But we know that the end product is histidine. We could get mutants.
His-minus mutants, which I've said up there, have the property of
growing only if you add histidine. So if we had just a minimal glucose
plate, just some salts with glucose and we were to streak a wild type
bacterium on it, it would grow just fine.
But if we had a his-minus mutant on a minimal glucose plate and we
streaked it out, it couldn't grow because it couldn't
make histidine. If it couldn't make histidine it
couldn't make proteins. But if we take the same plate,
minimal glucose plus some histidine, now this same mutant will grow
fine. And that's how we could tell that it
was specifically broken in making histidine. So if you were to go
into a undergrad lab, and I won't talk for the moment on
how you would isolate those his-minus bacteria,
it's not hard, you can do it in an undergrad lab,
you can make a whole lot of mutants that were broken in making histidine.
So one of the sort of things biochemists could do was they didn't
know what the intermediates were, but let's just say there's
intermediate-1, intermediate-2, intermediate-3,
intermediate-4 and intermediate-5. And finally it goes to histidine.
Well, if we break the gene that makes that, what will happen in that
pathway is the cell will make this intermediate, this intermediate,
and then this one will kind of build up. And, furthermore,
if I'm able to figure out what intermediate-4 is,
if I add intermediate-4 to this mutant it will grow because the
defect was earlier in the pathway. And if I added intermediate-1 it
won't grow. And so by sort of using very fine features of the phenotype,
I mean getting in there, breaking it open and discovering when
intermediate was up, or I could add an intermediate back
and forth, sort of playing with the phenotype you can learn a lot about
the mutants that you've isolated and so on. But genetics as --
And we'll sort of go into this just a little bit more.
But genetics as a science is able to figure out whether mutations are
in the same genes and work out their order without having to do any of
these sort of specialized knowledge of a phenotype.
It's a very general, very powerful way of doing business.
And I want to show you that. I want to use a system where we can
see this very clearly. And I want to introduce you to a
bacterial virus. The idea of a bacterial virus,
which are called bacteriophage, but it's just a bacterial virus.
And what's a bacteriophage? Well, it's got a protein coat of
some kind. They don't all look the same, but just some of them look
like this. So this is protein and this is DNA. That's it genetic
material. And it's basically a syringe. It's got a coat and it's
got stuff that will let it find a bacterial host.
And it's able to squirt its DNA from the bacterium into the host.
So if we take, for example, an E.
coli cell and this phage, which I'm drawing not to scale,
it would be smaller than this relative to the bacterium.
If it were to infect, it would inject its DNA into the E.
coli cell. And what it's sort of done is it's put a bunch of new
genetic information into a cell that's all capable of making
RNA and proteins. And so it kind of reprograms the
cell in the way I'm going to show you in a minute.
So when this new DNA comes in, this is the E. coli DNA. And the
virus kind of takes over the cell. And what it does is it makes it
into a machine or a factor for making baby virus,
if you will. So first it makes phage DNA.
And then it also makes the proteins that self-assemble to give [its code?
. So it's kind of reprogrammed the cell. And some of the viruses that
infect our cells are essentially doing the same thing.
They stick their genetic material into our cells and it takes over.
So unlike the retrovirus that we were talking about,
this thing is not inserting its DNA into the genome of the host.
It's just using the cell as a factory for making more of its own.
So then these assemble so that the host has now got phage inside it
like this. And the cells then lice, which means that they burst open.
The phage, once it's done all of this, makes a special enzyme that
degrades the bacterial cell wall. And it makes the cell pop open.
And it releases these free phage. And if you start with one of them
you might get, for example, 150 coming out of the
cell when it bursts. And then each one of these is able
to grab hold of another uninfected E. coli and start the cycle again.
And the cycle takes usually something like 20 to 30 minutes for
a bacteriophage. So it's pretty quick.
One phage absorbing to a bacterium, injecting its DNA can make that 150
copies of itself in about 20 minutes, and then each of those can infect.
So how would you detect something like this? Well,
the trick that's done is pretty simple. You take something like ten
to the eighth bacteria. Let's say you have some bacteria in
a test tube and then maybe let's say ten to the two phage,
and then you spread it on just a Petri plate that the bacteria
can grow on. So there are many,
many bacteria. So they're just going to sort of grow up and form
kind of a wand that will cover the whole plate. And if you were to
hold it up to the light you'd see it's sort of opaque now because the
bacteria have grown up. But anywhere there was a phage to
start out with, a single phage it would infect its
original cell, the cell would burst open,
it would release 150 phage, they'd infect the nearest 150
bacteria, they'd break open. And so what happens is the bacteria
trying to grow and cover the plate, the phage are growing and eating all
the bacteria. Basically at least using up all the bacteria in that
area. So what you get from this are little holes in the ìlawnî,
and they're called a plaque. That's the technical term. Here.
And so it's actually very easy to see how many phage you have because
you just put them out on a plate. And I realize this might sound
slightly fanciful. There is a textbook picture of a
bacteriophage with the DNAs all packaged up in the head.
It's got a sheath. It's got little things that will let it recognize a
particular host. And it really does look like a
syringe. And it's got stuff that squirts, basically the mechanics to
squirt the DNA in. There's an electron micrograph.
So that's a real one. This is not just a textbook cartoon.
It's a pretty accurate depiction. This was a little thing. This is
cycling, so don't get it mixed up. This only happens once. But this
is basically depicting the idea that the DNA starts out in the phage and
then it gets injected into the cell. And once it's in the cell the empty
coat, it doesn't have anything else to do in this story,
but the DNA takes over. And then you get, after a little
while, when you've made these progeny phage the cell breaks open.
And if you assay them, this is just a picture one of my
post-docs made for me. I think you can see here's a lawn.
You can sort of see how it's opaque and you can see those little holes.
There were probably a thousand or so phage that were put on this plate.
There are several hundred anyway. And you can just count the number
of holes and then you know how many phage you've got.
OK? So that's this system. Now, what I'd like to now consider
is how we could use genetics to try and study the essential functions of
that bacteriophage. How does it replicate?
How does it make its coat? I want to study the things that are
needed for it to be a phage, not something that's dispensable.
I want to know essential functions. So that means I would have to use
conditional mutants of some type so that I could study it because
otherwise if I broke something that was critical for the phage's life
cycle I'd never get any phage and I couldn't do any genetics.
So what I would do is I would look for temperature sensitive mutants.
The phage. So they'll form plaques,
let's say plaques at 30 degrees.
No plaques at 37 degrees. And you go through, and you could
be laborious or cleaver depending on how you set this up.
But we could make a bunch of mutants. And let's call T1,
T2, just give them names like that as I isolate them.
Now, what I want to show you are two absolutely standard and critical
genetic ways of analyzing these mutants.
They all look the same. Their phenotype is they form
plaques at 30 degrees. They don't form plaques at 37
degrees. They could be affecting one gene. We could have mutants in
50 genes. I don't know starting out. All I know is I've got mutants that
are temperature sensitive. So genetics gives you a couple of
ways of going at that that will tell you not only are they in the same
gene or in the different gene. But it also will tell you something
about their physical relationship along the DNA.
And this is without knowing anything about what they do.
So let me show you how that works. So the first genetic operation is
called a complementation test.
And the thing that I hope will strike you about particularly these
bacteriophage things is these are so simple. I've already told you
basically all the techniques we're going to be using.
We're going to be taking phage, we're going to be mixing it with
bacteria, we're going to be putting them on a plate and we're going to
be counting plaques. But we're not going to do anything
else and we're going to learn stuff about whether mutations are in the
same gene or different genes, between different mutants and
something about the order of the genes on the chromosome.
And that's the point I'm trying to drive home right now.
So here's the first idea. Let's add the T1 mutant plus the T2
mutant to some bacteria. So we'll put them both into the
same test tube. And what we want is enough phage --
So every bacterium gets both.
So we want to take, if we take T1 by itself it will grow plagues at 30
degrees, not at 37. T2 plaques at 30 degrees,
no plaques at 37. Now we're going to take some bacteria and put enough
that both of them will get into the same thing.
Now, of course, those bacteria are doomed because if
anything happens, because they've got things inside
them. So what we do now is then we add a whole bunch of what we would
call indicator bacteria. These are ones that haven't been.
And we'll put lots of those in, and we'll put many fewer of these and
we'll mix these together. And then we'll plate them out under
two different conditions. Let's try it at 30 degrees.
Well, in that case, I think we can figure out what would happen.
Both T1 and T2 can form plaque, so you'd expect to see plaques. And
you would indeed see that if you did this experiment.
Now, the other thing, though, this is where it gets
interesting, is what would happen if we plated them at 37 degrees?
Well, on their own neither of them can form a plaque.
But we've engineered it so that there are two within each bacterium.
So there are two possible outcomes, and let's think what they could be.
We could either have mutations in the same gene that some particular
gene, let's say a gene required for making the major protein in the coat,
that mutant one is affected in that gene and mutant two is affected in
the same protein. So both of them got a broken coat
protein. And so inside this bacterium, when the phage are trying
to grow, what you've got is this one gene. And this is the T1 mutant and
this is the T2 mutant. And maybe this one has got a
mutation somewhere and the other one has got it somewhere else in the
gene, but this gene is not functional.
So we wouldn't get any plaques. But what if they were in different
genes?
Let's say one of the mutants was altered in the gene for a coat
protein and the other one was altered in a gene that was necessary
for replicating the phage DNA. So it's a situation like this.
And let's say this is gene A and that's gene B.
What do you think could happen now? Get plaques? Wouldn't get plaques?
Yeah? I see a lot of nodding. We'd get plaques because this one
has a good gene A, so it would make let's say the coat
protein. This one has a good gene B so it could make the DNA polymerase
for copying the phage DNA. And things would be fine.
And so by this very, very simple test, we could take a whole lot of
TS mutants and we could go through in a pare-wise fashion,
and we could say oh, I see, number one, number seven and number
54 apparently affect all mutations affecting one gene,
and we could put them into categories by doing this.
And we haven't done anything other than mix phage and bacteria and look
to see whether they're plaques or not. I mean this is very different
than what a biochemist does. It's a different kind of thinking.
And yet it's enormously powerful. So this procedure,
which is one of the workhorses of a geneticist, is known as a
complementation test. And depending on the organism it
takes a whole bunch of different sort of technical forms.
But that's the principle of the thing, that if you have one good
copy of the gene and a broken one then you can survive in most cases
because usually the one will be enough to get you through here.
So that's one of the things that geneticists do.
And see how powerful it is for something that's a very
simple manipulation. But let me now tell you the other
kind of test that geneticists do. It's a slightly different principle
but just as powerful and gives you a different kind of information.
This is known as a recombination test. So what we're going to do in
this case now is we're going to allow two mutants to grow together
in the same cell. Let's say two mutants.
And we'll use T1 and T2 again to grow together in the same cell.
Now, for example, remember up here we mixed both of them in this so
they both were inside this bacteria and then when we plated it up,
up here at 30 degrees we got plaques? We would have gotten plaques from
every single infected bacteria. Well, those plaques probably have
ten to the ninth phage in them. And those were phage that grew
together under permissive conditions. OK? So let's take those,
re-suspend them --
-- and bring them over here. Now, we'll add them to some
bacteria. So bacteria in here. But we're going to do it under
different conditions now. We don't want complementation
taking place, so we'll make sure that we have less than one phage --
-- per bacterium.
So we cannot do this complementation thing anymore.
We just got rid of it by using a different ratio of phage to the
bacteria. So now what I want to do, I'm going to plate this out at 37
degrees. We could add an indicator if we wanted again.
Well, that may seem like a stupid
experiment in the sense that T1 wouldn't grow by itself and T2
wouldn't grow by itself at 37 degrees. And all I've done is let
them grow together. So if all we had in that population
was what we started with there wouldn't be any plaques.
But if you do that what you will find is you'll find
some rare plaques.
And these are what are known as recombinants. And let me now just
give you a sense of how these recombinants arise.
So let's imagine that this is the mutation and here's
our T1 bacterium. Here's its DNA.
And let's say there's a function here that it's wild type for and
it's got a mutation down here. The other one, T2 has got the
mutation here but it's wild type for there. That's the kind of thing we
were talking about, a gene A and a gene B,
although it's more general than that. But what happens when these things
are growing together is under rare circumstances this interesting thing
happens. Since this is the two strands of DNA and since these
phages are almost identical and this piece of DNA is the same as that
piece of DNA. And if a break every happened in one of these strands,
what can happen is it can invade the other strand and displace it.
And this strand can do a little switcheroo and come over here like
this. So now we've got the plus and the plus and the minus and the minus.
So this is an intermediate but these things happen.
You get little breaks in DNA from DNA damage and other things.
And the other piece of DNA can go off and pioneer and find another
molecule. And then there are enzymes that resolve this.
And if we cut it right here, we'd just go back to what we had
before. But if you cut this strand here, and you may have to sit down
and draw this out because this, for me, was not intuitive when I was
learning this thing. You'll see what happens now.
The end of this strand will go over and join to there.
The end of this strand will join and go here.
And what you will get out of that is one phage that's got both of the
pluses and one of the phage that's got both of the minuses.
And I'll call this sort of T1, T2 to indicate that it has got both
of the mutations. So this would be what we could
detect over there. That would be one of the rare wild
types. And I'll assert to you that this guy
here has two mutations in it instead of one.
What's the phenotype of the one that
has both mutations? It cannot grow. It can make
plaques at 30 degrees. It cannot make plaques at 37.
If I got up and said I'm sure this phage has two mutations.
It has both T1 and T2 mutations in it.
And I say prove it to me. Anybody see how you could do it
given what I've already told you?
Exactly. If I tried it in a complementation test with T1 it
wouldn't compliment because both would be broken in T1.
If I tried to complement T2 it wouldn't work because it's broken in
T2. And just by using these tiny little simple manipulations that
I've told you, I can even see that something that
has got a double mutant we could sort it out at the bench.
You could walk in and tell me the next morning what the result was.
In fact, phage grows so fast you might even be able to do it in the
morning and tell me before you went home at night.
So this is, as I say, called a recombination test.
And it's giving you a different kind of information,
but it's an extraordinarily powerful technique for another reason,
is that the recombination frequency can be measured.
We'll call RF.
And this is the recombinants over the total. So,
in our case, this would be the number of wild type,
plus the number of these double mutants over the total of T1 plus
the total of T2, which would be the dominant members
of this population. Because this is a relatively rare
event, plus the wild type, plus the T1, T2. And the thing that
is so useful is the probability of, geneticists call this a crossover,
this kind of crossover happening is proportional to the distance between
these things. If they're a very long distance
apart there's a lot of DNA, and the chances of it happening are
much higher than if the two mutations are very close together.
It makes sense just from First Principles. So the recombination
frequency varies as the distance --
-- between the mutations. So let's imagine that I do a cross
like this. We'd grow T1 plus T2 and we measure
the recombination frequency, and I find that it's 4%. 4% of the
plaques are mutants out of everything that's in there.
And let me try another one. I'll take T2 and I'll cross it with
the next mutant phage of isolated T3. And let's say,
in this case, the recombination frequency is 5%.
Because I know they're different distances, but if you think about it
you'll realize there are two kinds of maps we can draw.
These data are compatible with the gene order being one,
two, with this being a distance that corresponds to a 4% recombination
frequency, and three with this being the distance that corresponds
to the 5%. But it's also compatible,
isn't it, with this where we have one, two and three here.
There's the 4%. And from there to there is the 5%.
Yeah, that's right. Two to three. One to two is 4% and
two to three is 5% in both of these.
One to two is 4%. What did I do wrong?
Two. I guess I've got to do it this way, two,
one. Is that going to do it? What did I do with my example here?
Yeah. Hang on a second. OK.
Let's go back to where I was and see if I can reconstruct this.
OK. There's one, and two is 4%, and we want two to three 5%. OK,
right. So it's going to be here. Here we go. Two to three. Excuse
me. It's got to be farther over here. There's three.
There's the 5%.
OK. Now we've got it, once I change these numbers.
The 4%, the 5%, the 4%, the 5%. OK.
I thought I was over this cold. I guess I'm not quite over this
cold. OK. Could you devise an experiment that would distinguish
between those maps? Yeah? Yeah. You've got it.
Take T1 and T3. One of those you'll get a 9%.
One of them you'll get a 1%. Isn't that amazing? I mean it's so simple,
but I think you can perhaps see some of the power of genetics here.
All we've done is we've got things that we know can form plaques at 30
and not at 37. We haven't done anything other than
mix them with bacteria and then count plaques.
And we've been able to make inferences in a living organism
about mutations in genes that are absolutely essential for that
organism to grow. So what phage geneticists were able
to do over the years then was they would make a map of all of these
different genes down to the phage genome and then the biochemist would
go in and work it out. And people studying mice would make
maps of genes along mice. And it's only been in the last
handful of years we've been able to go in and sequence the DNA and find
out where all of these things are. So I will see you guys after. I
hope you have a wonderful spring break. And I think you'll really
enjoy hearing Penny. And we'll start in on diploid
genetics and Mendel and stuff as soon as we get back.
OK? So see you in a little bit.