Julia just mentioned that a few of you had commented,
when we were talking about the genetic code,
that some of you thought the fact that it
was degenerate, it had some redundancy in it,
like multiple codons or threonine,
that that was kind of cool, and some of you
thought it was sort of a waste and would have maybe designed
the thing differently.
That's, you know, part of when you study biology
you don't get to design it from first
You found out what happened during evolution and what got
And once it gets selected for then that gets sort of fixed in
If there were four nucleotides then you could have one,
two and three-letter words.
And it's going to be a three-letter word to have at
least 20 then you've got some degeneracy or redundancy,
but that's not necessarily a bad thing.
And, in fact, if you go into the
evolution of the code more deeply, people are beginning to
suspect it evolved from a simpler one.
And there actually are some relationships between some of
the codons that go back to the similarities,
the chemical similarities between the amino
And it also allows some things for some cells,
for example, if they want proteins to be
present at very low levels they will use a
codon that has just a very low level of the corresponding tRNA.
And if they want to make a lot of the
protein they'll use a tRNA that it
makes in abundance.
And so it's sort of another way of
controlling levels of proteins.
There are a lot of different subtleties in here.
And also in biology redundancy is not
necessarily a bad thing.
It's just like on a space flight, if something
goes wrong and if there's some kind of redundant function then
you've got some backups,
Well, in any case, today is a pretty
interesting first part of the lecture.
I've heard a few people express the view that why can't
I just teach what's in the textbook
and get on with it?
And I think this part, for those of
you who are following, really trying to understand
what I'm trying to do with this course,
I hope this will help you to see this.
Because what I've talked about,
this thing that Crick called the "central dogma"
which was the direction of information flow in biology
which was from DNA to RNA to
And I'll just remind you, although
proteins do many things they are, for example,
enzymes that are biological catalysts.
And it was pretty well-established,
even by the time I was an undergrad that
this was the way information flow went in
biology and this was how it worked.
And there were various statements in
the literature that what was true for E.
coli was true for an elephant.
And it is still true today in a broad sense that,
as I've tried to emphasize throughout the course,
when you get down to a cellular molecule level there's an awful
lot in common and things look much
more alike than different compared to
what we see at a more macroscopic scale.
However, that doesn't mean that all the details are the
And maybe you could begin to get a
glimmering of that when I told you that although the genetic
code is virtually universal.
That almost every organism, with
only a couple very tiny exceptions, uses exactly the
same genetic code to have nucleotides correspond
to three-letter words in the nucleic
acid alphabet correspond to particular amino acids in a
But the other languages that are written in there such as the
sequence to start transcribing a gene, making an RNA copy or
Those are different between different organisms.
Glycolysis enzymes are amazingly
They are very clearly, they arose once,
and they have stayed right through evolution.
You could, in principle, sometimes in
evolution you get something that creates a function and
something that starts out,
and then like what they call convergent evolution you
end up with two things that came from a different
evolutionary origin but have learned to do,
let's say, catalyze the same biochemical
reaction or something.
Glycolysis came once.
But if you were to look inside E.
coli or yeast, let's say E.
coli and look at how those enzymes are
regulated, the thing that says this is the start of
a gene, start making the RNA, it would look totally different
than if you looked in a mouse because
the language, the promoter does not have
the same sequence in an E. coli and in a human or in a
And I'll tell you more about that today.
But there were -- I want to just now tell you
sort of three things that were sort of
exceptions to this general way of thinking.
Every one of them generated a Nobel Prize.
And this is a fun lecture for me to give
because the individuals involved in all of these things
had a very, very close association with MIT.
And when I told you when Crick called
this a central dogma he meant a hypothesis, or at least an idea
for which there was not reasonable
And he learned later it was something a true believer cannot
And once this gets established it does get in the
textbook and it does get in your thinking.
And so information goes down this way.
But there were a few oddities.
I mean there were some viruses that had RNA inside
They didn't have DNA.
So how where these handled?
Well, there turned out to be two
classes of RNA virus.
One that was studied quite heavily called,
it's a plant virus called the tobacco
And it had a coat.
And then it had in it a piece of RNA.
Now, you can see if that virus were to inject RNA in the cell
it could encode proteins.
But that genetic material has to be copied.
And the RNA was copied -- -- by an RNA dependent
And so it's sort of just like the
RNA polymerase before, except instead of using DNA as
its template it can use RNA.
So that sort of somehow would be a little loop in
here about RNA being able to copy itself that hadn't been
And although this is an important virus in the plant
industry, for plants and agriculture,
it's not so important for humans.
But there's another class of RNA viruses that are very
And these are called retroviruses.
And the reason these are so important is that the HIV-1
virus that's associated with AIDS is such
It's a virus that has a coat and it has an RNA that's its
And the person who worked out how
this goes was a person at MIT, Dave Baltimore.
He was a colleague of mine here for many years.
He was the person who founded the White-
head Institute and got that up and going.
And he then finally, to move
up one more administrative challenge, went to Caltech
to be president.
And that's where he is today.
And David was working on this
problem trying to figure out how these
And they're important.
Not only the HIV-1 virus, but there are certain
viruses that are associated with cancer.
In general, what they do is
they've picked up what's called an oncogene
which is sort of often a mutated version of one of your
And if that virus gets inside one of
your cells and brings in this mutated gene it's sort of kind
of the same consequence as
mutating one of your own genes along that
progression of cancer.
So it can kind of, say, bring in a cell that
screws up the control on when cells are supposed to replicate
and stop dividing and so on.
So David started to work on these, and what
he discovered was that these viruses encoded,
they had information encoding proteins.
And one of the proteins encoded in
their RNA is an enzyme he characterized which is given the
name "reverse transcriptase".
And what this can do is take an RNA
template and make the corresponding complimentary DNA
strand in this way.
So that if we took the -- We'll just take this RNA out of the
What this virus encodes then is an enzyme that's able to take
this RNA and make the corresponding DNA copy.
So there's the original RNA that was in the virus.
There is the RNA that it started out.
And so what is happening,
if you will in that case, is the information is
flowing in the other direction.
That was a marvelous discovery.
And it was discovered by someone who
wasn't willing just to take what was in the textbooks but
was trying to figure out what could possibly
be going on here.
Now, the way these viruses work then,
once they've done this it's not so bad because they've
got their information now in the form of DNA.
So this strand of DNA can be made into a double-stranded DNA
by just using the kinds of enzymes that
we've already talked about.
A DNA dependent DNA polymerase will
be able to copy the other thing.
And now you've got a DNA copy of
the information that used to be in the
But what happens to that is that you have a piece
of the host DNA.
And this viral DNA then inserts into
it, so you end up with this situation where you have DNA
from the host, and this is the virus
So this is the DNA that encodes the information needed for the
And if this was our DNA then it would be inserted that way.
And there are just a handful of
health messages I've tried to drive home in
I mentioned smoking the other day.
If you smoke -- If you stop smoking you
basically, well, let me try another way.
The risk of smoking is about equal
to the sum of everything else you can
possibly do in your life that will affect your chances of
getting cancer, leaving aside what you
inherited from mom and dad.
The one single thing to not do if you
want to avoid cancer, or to help loved
ones who smoke avoid cancer, is just don't smoke,
or if you do smoke, stop.
You freeze the risk of whatever increased risk you've got,
and then just live with that, but it doesn't
keep getting worse with time.
The other one is practice safe sex, and
this is why.
HIV-1 is a retrovirus.
If you get infected with it, it
makes a DNA copy of the RNA, it makes the other strand of
the DNA, and it sticks itself in.
So what you've got is your DNA here, your DNA there.
And HIV-1 is a permanent traveling
companion for the rest of your life.
There's no way of getting that out
of there right now.
All the systems for dealing with AIDS are just
managing the infection.
So when someone is HIV-1 positive, they've
got those viral genes now permanently integrated
into their DNA.
So it's extremely important that you
be aware of that, or if you know people who don't
appreciate this because they haven't got so
much of a biology background that you help
them understand that.
So I just wanted to show you, I found one
other picture last night.
And this is you see all these old scientists,
Of course, David didn't look like this when he was doing his
In fact, I think he's fairly cleaned up here.
I found this one in the Cold Spring Harbor
archives last night.
I've seen pictures of him looking considerably more shaggy
and perhaps disreputable and stuff.
But anyway, when David was making all these
discoveries he was still quite a young man.
I believe he got his Nobel Prize when he was still
in his thirties.
And so many of these discoveries are made by people
that are not all that much older than
But, again, it's trying to understand why we know what we
know and then trying to fit other
things into it.
Now, the next thing I want to tell you about that has some of
this same character, I've sort of told
you that you have a piece of DNA.
Let's say there's a gene here and
this is the coding region, and then we make
a mRNA copy, and then we use the genetic
code and we make the protein.
And so if we sequence the DNA and
find the beginning of this protein we can read along using
that genetic code and away it should go.
And that was beautifully worked out,
understood, just like I sort of finished up telling you the
So Phil Sharp who got a Nobel Prize for this work and is a
colleague in the Biology Department.
He's in the Cancer Center just across the street from the
building I'm in.
That was the cancer center that Salvador Luria,
who Jim Watson trained with,
And Phil was studying this process.
It was before we could sequence DNA.
It was in the mid '70s.
And he was working with the tools we had
then trying to map the relationship of an
RNA to a gene that was on a virus.
It was a DNA virus, not an RNA
virus, so don't get yourself mixed up with that.
But what he had was basically a fragment of DNA
that he knew encoded the gene.
So he knew somewhere on this piece of DNA
there was a gene somewhere in here, and he
had isolated the mRNA.
And one way you could map, physically see the
relationship of an RNA and a DNA would be to take,
let's just take away one of these strands.
So we have the complimentary strand
of the DNA to the RNA.
And if we mix them together and let them
slowly cool down they will form hydrogen bonds.
They'll form a DNA-RNA hybrid just the same
way two strands of DNA come on.
And so if the gene was a little shorter
than the piece of DNA then you might have
expected to see something that looked like this.
And the way you'd see this, if you looked in an electron
microscope -- -- perhaps it would look sort
of like this.
You cannot actually see the two strands, but you'd see a
That would be the RNA duplex.
So this would be just DNA.
And the thick part is RNA base paired with a single strand of
You got it?
That's what textbooks said you should have seen.
And so this is more.
This is data from Phil's paper describing this.
And let me focus on this one in
That's what he actually saw.
You guys got any idea what's going on?
Why don't you take a minute, find somebody who's near you
and see if you can come up with any ideas.
Here's the hybrid.
Forget about this little bit at the 3 prime end.
That's not a worry.
Here is the thing.
And this, I think, is a
piece of single stranded DNA sticking out the end.
But it looks a bit more complicated.
Most people put this data in their drawers.
Phil and his colleagues didn't.
What they realized was, I'm going to try and redraw
this just very slightly to help you see what's
What they were seeing was something that looked rather
like what they were expecting.
They were seeing a region of hybrid DNA and they were
seeing a region of single-stranded DNA like this,
but what it looked like was there were little
loops of single-stranded DNA sticking out.
And what Phil had discovered was a phenomenon we now know
as RNA splicing.
And here's what goes on.
In bacteria, with very few exceptions,
you can look at the DNA, you can find the open reading
frame and you can just read off the sequence
of the protein.
You find the ATG, AUG,
methionine codon, and then it keeps going no
stops, and finally you come to a stop codon and you see
there is the protein.
So the coding information is essentially
continuous in almost all bacterial genes.
And there's a few, some genes like
that in eukaryotes, but many eukaryotic genes are
constructed, it's almost as if you took the
gene you'd find in a bacterium and then
you'd cut it in a bunch of places and stuck extra DNA in
between all of the pieces.
So you'd get something like this where there's,
in the DNA there'd be coding information.
And then non-coding information and another block of coding
And then a block of non-coding and say another one of coding
So this is a double-stranded DNA.
And what happens then when the cell
makes RNA is the whole thing gets copied into
what's known now as a pre-messenger RNA.
And so there's a bit of coding stuff here, there's a bit of
coding stuff here, and there's some more
coding stuff there.
But what the cell has is sort of like your unedited
footage from your family summer vacation when you were running
the video camera.
And maybe you don't want to show everybody ever second of
video that you took during the thing.
So what you do, you get in there and you
In the old days you used to have to take the film and splice
And now you can all do it with iMovie or something like that.
But what you do is take the pieces
of information you want, and this is
what the cell is doing.
It takes this part of the RNA.
And this part of the RNA, and joins it together,
and then this part.
And when it's done it has the mRNA that now looks like the
kind of mRNA that you would find in a
bacterium where you can find the start codon.
And then you could read in three-letter words all the way
through to the end of the protein.
So, in essence, what Phil found was
that in many organisms at least there's another step in here
where we get RNA splicing.
And only after that you get down to proteins.
What was quite remarkable about this result and why I'm kind of
hammering on it a little bit is this is
the data that's out of Phil's paper.
You can look it up on the Internet.
Type in Phil Sharp 1977 and you'll
find this original paper with that figure in it.
The moment Phil realized what it was and talked
about it at a meeting, a whole lot
of people suddenly sort of almost simultaneously discovered
RNA splicing because they opened
their drawers and there were all these
uninterpretable electron micrographs they had.
And they were in very short order able to save it in the
The same thing was going on,
but it was just confusing, it didn't fit,
and to some extent most people's
minds were set by this paradigm, this
central dogma as something that a true believer cannot doubt.
And you had to have a flexible enough
mind to be able to see that.
And so this is an important piece of biology that hadn't
And it can be quite remarkable.
I'm just going to give you a couple of extreme
Well, not even extreme examples.
But just show you how much non-coding information there can
Factor 8 is a protein that plays a part in blood clotting.
And the gene is 200 kilobase pairs.
And the pre-mRNA is just a direct
copy, so it's 200 kilobases.
It's just a single strand so it's not a
And the actually spliced mRNA when it's done is 10 kilobases.
So that means that only 5% of the gene is coding information
and 95% of that information gets thrown
away when the RNA gets spliced.
And even a more extreme example is a protein called dystrophin.
This is what's affected in a human
genetic disease known as Duchenne
In this case, the gene is two mega- base
So of course then the pre-mRNA is also two megabases
but the pre-RNA is 16 kilobases.
So in this case less than 1% of the
gene has coding information for making a protein.
There are a lot of interesting reasons as to why it would be
One this, things can evolve more rapidly sometimes because
you have parts of proteins that are sort
of like modules and evolution can probably connect them.
In fact, it also provides ways of regulating because we now
know there are alternative ways of
So you can take one RNA and then splice it in different
ways in different cells and end up
generating different proteins that were all encoded by one
And so it gives cells different kinds of regulatory
strategies they can use.
Now, the third sort of thing that
came out that falls in this same kind of thing of people
having their minds open and not fixed by the
current understanding or bounded by
the current understanding is the discovery that RNA can act
as an enzyme.
And I've already talked to you about that and I've told it was
ribozyme, but it was discovered by Tom Cech.
Tom is currently president of the Howard Hughes
Medical Institute, but he did his
post-doctoral work at MIT with Mary Lou Pardue.
I'd been a post-doc at Berkeley when he was just finishing his
graduate work, and I met him out there.
And then he came to MIT to do his post-doc.
And a year later I got a job so I'd become friends
there and became friends when we started here.
So I had a pretty close link to this particular
Here's a picture of Tom together
That's actually my wife right there who was in this picture.
But Tom actually looks much more like that.
He's very colorful, very fun, a very interesting
But anyway, when Tom left MIT to take a
faculty position at Bolder he was interested
in trying to understand the biochemistry of RNA splicing.
And so he went -- He did what a good scientist will
They'll try and find an experimental system where the
question they want to address is simple enough you can
actually get an answer.
There's a kind of way of doing science where you pick a
system that's too complicated and you never actually get an
It sounds very important because you're working on
something that's important but you cannot,
you don't have the tools you need to get to
So Tom wanted to work on the biochemistry of RNA splicing
because that had just been discovered.
And so he went to a small little tiny organism called
And the reason he looked at that was because it had a
ribosomal RNA, so
it was an RNA that was made in great abundance within the
And it only had one of these
I'll tell you the words for these coding and
To me they're non-intuitive, but I
guess you should know them.
The coding region is called, the
part that codes is called an exon and the non-coding part is
called an intron.
So, anyway, Tom worked on this organism because the pre-mRNA
was basically this.
Or the pre-mRNA before the splicing
looked like this.
This was going to give this like that.
He could get large quantities of this RNA,
so he was all set to make extracts of the
cells of this organism and then start cooking up this RNA
substrate with all sorts of cell
And then his plan was to purify the
enzymes that did the RNA splicing.
And so I first heard about this, Tom
was working on this when he was here.
And he went off to, I guess
it was Denmark to learn how to grow this organism.
Then they were back and he was off at Bolder.
And we used to play squash all the time.
And whenever I got out to Bolder we'd try and get in a
So I was out there at a meeting and we were sitting around in
the locker room.
And I said so how's the splicing biochemistry project
Tom says, well, it's going OK,
There's only one little problem,
The controls are splicing.
Now, what he meant was if you were trying to
add cell extract and get this thing to
go what you would start out with is the RNA in a tube
And that would be your control.
And then you'd start adding stuff to it
and start looking for splicing.
And what Tom was finding was that if you
just took this RNA and let it sit in a test tube that the
splicing happened without him putting
And here he was already to find all the
enzymes, the proteins that did it.
And Tom did an absolutely gorgeous piece of
science to prove that what was happening was the RNA was
catalyzing its own splicing.
And he had to work very, very hard to prove that it
wasn't a contaminating protein.
Remember we had this sort of discussion?
We were talking about is DNA the
genetic material and how would we
know that it wasn't just a little tiny bit of something
else in our DNA perhaps that was doing it.
Tom had to go through pretty much a
similar exercise, but this was one of these key
insights that lead to the proof that RNA could
function as a catalyst, what we now
know as a ribozyme.
And I've shown you now we now sort
of accept that the actual ribosome itself is a ribozyme
and that the formation of the peptide bond,
the thing that's the heart of all
proteins is made by a ribozyme, not catalyzed by ribosomes and
not by a protein.
So the next topic that I want to try on which sort of
we've already set up from this is that if the information is
all in DNA to begin with then if you
make an RNA copy you're only taking a
segment of that information at a time.
And that gives the cells a lot of possibilities for regulating
how they respond to the environment
or just controlling what genes are
And there are basically two kinds of strategies that are
involved in these regulatory decisions.
They can either be -- Can either be reversible
For example, a bacterium and a food source.
If you're a bacterium and you've got enzymes that let you
eat a hundred different kinds of food
and you're in an environment where there's only one of them
there, you're really wasting energy if
you make the proteins to make the other
So you might guess that somehow evolution has selected for
systems that have learned how to turn
on and off the things they need to eat
certain food sources depending on whether the food source
We only carry umbrellas when it rains.
If you had to carry an umbrella and a snowsuit and a
surfboard, everything all the time, it would slow you down in
So the other type, which we've talked about as
well when we talked about starting as a single cell
and going to the 10^14 cells that make
us up, then many of those changes, as those cells go along
and progressively more specialized
need to be irreversible.
And this is particularly important
We don't want a cell in our retina suddenly deciding
it should be part of a heart and start to make a heart in the
middle of your eye or something like
So things in development tend to be
once you're off you're off or once you're on you're on or
And just to give you another little look at that picture I've
shown you before of the nematode.
And at the time, the first time I
showed you this, I was just trying to emphasize
that we could take the gene encoding green fluorescent
protein and put it in anything and
it would go green.
In this case, Barbara Meyer who is at
Berkeley now but used to be my office-mate
at MIT for many years, what she's done is
she's taken that green fluorescent protein,
the gene for that, and
she's put it under the control of a regulatory system,
a gene that is made to be expressed in the
esophagus of the worm.
And so even though that gene is present in all the cells of that
organism, it's under the control of a system that usually
permits the genes to be made that are
needed for making esophagus but not in other
parts of the body.
So you probably didn't pick that part up now but
sort of take another look at that same thing and see
So how do we learn about gene regulation?
The key work, like so many of these things,
started kind of inauspiciously,
if you will.
There were two French scientists, Jacques
Monod, who is a biochemist, Francois Jacob who was a
And they were working on the
metabolism of lactose by E. coli.
Lactose is galactose, beta 1,4 glucose.
And you don't have to know exactly the structure.
You can just remember there were a lot of
different hydroxyls, and that was one particular
And there's an enzyme that cleaves this
into galactose and glucose.
And this can go right into glycolysis and
make energy for the organism.
And the galactose undergoes a couple of different
transformations, and it
can get in there as well.
But in order to get at the energy that's in
those carbohydrates, this linkage has to be broken.
And it was broken by an enzyme called
That's a protein that's able to catalyze
the cleavage of those two sugars.
That's what Jacques Monod and Francois Jacob were studying.
They were helped out in this
I guess part of the reason they got
going on this was people had noticed for many years that if
you grew E. coli in glucose there was no
I'm going to abbreviate this as beta-gal just so I won't have to
keep writing the same thing.
But if they grew E. coli in lactose
beta-gal was present.
And they had to be able to assay for this enzyme.
And they used -- There were standard types of
biochemical assays you could use.
But some chemists that helped design a very cleaver kind of
substrate that helped them,
that could be used in these kinds of studies,
and I'll show you one of them.
What this enzyme really looks at is it looks
at, let's see, galactose.
What it sees is sort of the galactose side of this linkage,
and then it reaches in and catalyzes the
cleavage of what's joined to it.
And it turns out not to be specific
for whether glucose is on the other side.
It can accept substrates that have other things as well.
So some chemists made some variants like
This is a compound that's commonly known as X-gal.
If you talk about it in the lab it's
got a longer chemical name.
But what happens if beta-galactosidase is there,
it's able to cleave this substrate
so you get galactose, which is colorless.
But if you get just X, this is colored,
but up here this original material is also colorless.
So this is very convenient because if you
use a substrate such as this you could put the cells on a
plate with this indicator.
And if they are colored, and the
color is blue, you'd know they were making
And if you don't see a color,
you know they're not.
There are a variety of ways of assaying for this
With that I'm just trying to give
you a little bit of flavor of one of the different ways that
they could assay for it.
Now, one of the issues was it looked as though E.
coli didn't have any beta-galactosidase activity if
lactose was absent when growing in glucose.
And they made it if lactose was present.
Well, that would be kind of what you would expect
evolution would have figured out how to do,
only make the enzyme for metabolizing lactose if the
lactose is present, but they had to
figure out what the molecular basis of this
And one of the possibilities was that the protein was made
that it was all sort of unfolded,
and when the substrate came in then it
folded all around it and then it could cleave it.
Or another possibility, which would be the kind we're
talking about now, is the protein is not made
until the lactose is present, and then it
makes it new.
So they had to figure out, between these two,
which of these two was true.
When you see the lactose present, is it just
beta-galactosidase is already made but it's inactive,
or is it being made de novo when you add the
So what they did was they grew cells in glucose plus
radioactive C14-leucine for a long time.
So all the proteins -- -- were radioactive.
And once they got, that's going for a long
So every protein being made is radioactive.
Then they add excess unlabeled leucine.
So this means that from now on any new proteins that are
made will not be radioactive because you're just going to
swamp out any radioactive stuff with this.
And they added glucose, excuse me, now
they added lactose to the cells.
And then they isolated the beta-gal enzyme.
It was actually pretty easy to do.
It's a huge enzyme and it's a tetramer.
So very large.
Even in those days it was fairly easy
to isolate this enzyme.
And then they looked to see is it
If it's radioactive it was there all
along and it's refolded to become the active enzyme.
Or if it had been only after lactose then it would be made de
novo in response to it.
And what they found was that it was non-radioactive.
Which implied that it was made after
you added the lactose.
So they knew then that they were
studying a system in which a protein was only made after the
cells had experienced a particular growth
And so a lot of work went into figuring out how this
We're a little short on time.
So I'll tell you what I'll do.
I'll tell you, I'll just put out
quickly the mechanics of what they saw, and
we'll start in on the regulation on how this works.
And some of you may be able to figure it out.
What we now know is that the gene that
encodes beta-galactosidase is in a stretch of DNA that's
It's got three genes.
It's the gene lacZ.
This is the gene for beta-galactosidase.
And another gene called lacY and
There's a promoter.
That's a start signal for transcription.
So there's a sequence here that says start
Down here is a terminator.
Another word written in the nucleic acid alphabet that means
stop making mRNA.
And there is one long mRNA, as you can see,
that has the peculiarity of encoding three
So if you have more than one gene in a single
message then that's called an operon.
You've got one mRNA.
But, in any case, so whenever beta-galactosidase
was being made then RNA has to start being made here,
goes to there.
And we won't worry about the
functions of these other two genes.
But, as you might guess from the way evolution has selected
for it, they have related activities to what
And for bacteria it's a very efficient
way to control the expression of a bunch
of genes at once.
Then there was another gene up here known as lacI
that had a promoter and a terminator, and it made
an mRNA as well.
And that mRNA encoded a protein that's known as the lac
And what that lac repressor does,
it's a protein that has the ability to recognize a very,
very specific DNA sequence and bind there.
And I'm just going to kind of blow up
this part of the thing.
So what we have here is the, this is
the promoter here.
And it happens that the binding sequence --
-- for lac repressor overlaps with
So I'll tell you, well, you can think about this
over the weekend, if you haven't run into this
So this gene gets made all the time.
So this protein gets made all the time.
What does that protein do if it's just like
Its job in life is to look for this
sequence and bind to it.
If it binds to it, it covers
up the promoter.
And the beta-galactosidase gene is
not expressed because the cell cannot make mRNA.
So this may seem a little obscure,
but there's something very important here.
Now the conditionality on whether
this gene is expressed or not is controlled by a protein,
It's controlled by this lac repressor.
If it's on there the gene won't be made.
And if it's off the gene now you can make
There's a promoter and the RNA polymerase will see it.
And so you've learned something about
They can bind various things.
And so what lac repressor has, it's got a little binding
site that lactose is able to bind to and
change the confirmation of the lac repressor.
So why don't you take those pieces of information and
see if you can figure out how the circuitry goes.
Did I do something wrong?
We'll walk through that on Monday,
but focus on the fact that if the repressor is
there and lactose isn't, it binds to this sequence.
The repressor is made all the time, but this repressor is
something that can tell you whether lactose is
there or not.
So you can put the circuit together, OK?