- [Instructor] The last
15 minutes or so we have,
I'm just gonna give you
a brief introduction
to chapter 10, or
lecture 10, I should say.
Now, we're at the hump,
meaning we're halfway through, yay.
So we're at the lecture 10
point, they're 19 lectures,
so we're pretty much
right in the middle here.
We've gone through the first
two characteristics of life,
which is how life is organized,
and how life uses energy.
We've talked a little bit
about how life maintains homeostasis
and we'll continue to talk
about how life maintains homeostasis
through these processes,
but what was the fourth step?
What was the fourth characteristic of life
that we learned back in lecture one?
All living things must reproduce, good.
Reproduce, grow, repair, and
the like, so on and so forth.
Okay, so in fact, the next six
lectures are purely on that.
I mean, when you think biology,
you usually think reproduction.
Because we devote most
of our time and energy to that process.
I'm not just talking about sex,
I'm talking about other factors.
All right, so what's included in these?
What's included in reproduction?
Well, we're gonna talk about cancer.
We're gonna talk about
what we call biotechnology
where we look at stem cells
and genetic manipulation
and things of that sort.
So when we talk about reproduction,
we primarily look at
the inheritance of DNA
from one generation to the next.
So this also brings into fact
a process called mitosis,
which is cellular reproduction,
also myosis, which is sexual reproduction,
and we'll look at inheritance,
which is the passing on of our genetics
through either sexual
or asexual reproduction
from one generation to the next.
So you can see, there's a lot of topics
that are covered by this
one characteristic of life.
So what is lecture 10 all about?
Well, in order to understand
what causes cancer
and why cells become cancerous
and what mitosis and myosis is
and how you inherit genetic material
and how you manipulate the genetics
and how you inherit the genetics,
we first have to talk about the genetics.
That's what this lecture's all about.
What is DNA and how does DNA work?
How does it get inherited?
What makes it up?
How does it encode information?
The main purpose or two processes
that are gonna be found in this lecture
are shown right there,
transcription and translation.
No matter how many times
I hammer this home,
people still get those two words confused.
So let me give you a pre-cursor to it.
Back in the days, before they had copiers,
the monks tediously read the scriptures
and other types of
documents and copied them.
Transcription, or to transcribe something,
is a copying process.
So transcription is when
the cell copies its DNA.
Now there's two ways in
which this can be done
that we're gonna go over
through this lecture.
The second word is translation.
What do you think of when
you think of translation?
To translate something?
One language to another language, okay?
So when you translate something
from one language to another language,
like in Spanish to English
or Russian to Chinese
or whatever the case may be,
you're literally doing
works that mean the same
but in different languages.
Well, that's the same thing here with DNA.
We're gonna show how
DNA gets copied into RNA
and RNA gets translated into a protein.
'Cause remember, DNA and
RNA are the same group.
They're in the nucleic acids groups.
So when you copy one to
the other, transcription,
that's a copying process.
However, when the ribosome reads the RNA
and turns it into a
protein, that's translation.
These are two separate biological groups.
If you think of them as
two separate languages,
which they really are, then
that's what the ribosome is,
it's the translator,
it's the one that says,
okay, here's the RNA information,
here's how I make the protein.
So those are the two processes
we're primarily gonna focus on,
transcription and translation.
So before we can get to that,
we first have to have a
really good understanding
about what DNA is and how it's encoded.
How do we have information
contained in these biological molecules?
Now, you guys see a lot of scientists,
as we discussed some of these things,
and I'm not so interested in
having you memorize history,
but it is good to mention how recently
we've discovered these things.
Now I know that 1950s may not
be recent for most of you,
but that's not that long ago.
Which means, we have only
scratched the surface
in the last 60 some odd years of DNA.
It wasn't until 1953 that we even knew
what DNA looked like.
Then it was another two decades
before we can start manipulating DNA.
And then it was another
two decades after that
before we could actually start reading it
and now here, a decade or so later,
we can do amazing things with this.
So it is increasing exponentially
as far as our ability
to manipulate DNA and understand it,
but it wasn't that long
ago that we discovered DNA.
Now I say we, Watson
and Crick are the ones
given the Nobel Prize,
but I like to make mention
to a Rosalind Franklin.
She was a scientist of her day,
which was actually rare
back in those days,
and we have a lot more
women scientists today,
but that was a rarity back then
to have someone that was
very well established.
Now she died of cancer before
the Nobel Prize was given out,
otherwise she would have
been awarded as well.
She was the one that gave Watson
and Crick that last piece,
which was that double helix
structure that DNA is found in,
they were missing one last little piece.
All right, so let's look
at how DNA is organized
and what it looks like and how it contains
the information that it contains.
Now if you remember back
from when we studied organic molecules,
DNA is a polymer made of monomers.
The monomers are called nucleotides.
The nucleotides were made up
of three fundamental parts,
remember what they were?
Phosphate, sugar, and a nitrogenous base,
that is a nucleotide.
Those are the monomers
or the building blocks
of nucleic acids, whether it's DNA or RNA.
Now if it's DNA, you
have a deoxyribose sugar,
if it's RNA, you have a ribose sugar.
That's the main difference
between DNA and RNA.
Although there are some more
subtle differences as well.
Now the nitrogenous basis,
'cause they've got a
lot of nitrogen in them,
there are four for DNA.
We call them adenine, thymine,
cytosine, and guanine,
A, T, C, and G.
So the first thing that
you're gonna have to know
is that DNA being a double helix ladder,
the opposing strands have
what we call complementary nucleotides,
which mean that the basis
will actually pair with one
another in a certain way.
As always pair with Ts,
and Cs always pair with Gs.
That is the universal, what
we call base pairing rule.
So if you see a T on one side of the DNA,
you know that the other
side's gonna have an A.
If you see a G on one side,
you know the other side's gonna have a C.
Those are the universal pairing rules.
Anybody ever see the movie Gattaca?
Wanna know where it's got its name for?
Yeah, basically the basis of DNA.
'Cause the movie's about DNA
and genetics and all that.
Anyway.
Okay, so what holds DNA
together is hydrogen bondings.
And the reason for that
is because the only way
that DNA could be read like a book
is to be constantly opened up and shut.
Some of you may not have ever opened
your book this semester,
you may not even have it,
but for those who do have your book,
you know that you open and shut it a lot.
Well, if the pages were glued together,
it'd be very difficult to
open and close your book
to be able to access that information.
So hydrogen bonds allows
the DNA to be held together
as a long string of polymers,
but is weak enough that
enzymes can come in here
and unzip it, read it, and
then put it back together.
So that's why the double helix
is actually held together
by hydrogen bonds.
It's because it's
constantly being opened up
and put back together for various reasons,
primarily to access the
genetic information.
All living things on this planet have DNA,
but the DNA is organized
a little differently
depending upon the type of cell.
For example, prokaryotic cells,
which are the more simple cells,
tend to have a circular
DNA that is their genome.
Now, they're much circular,
so they don't have as many,
what we call genes as you and I,
but their DNA is like yours and I
and that is double stranded,
they use the same nucleotides,
As, Ts, Cs, and Gs,
and in fact, the code that
it uses to store information
is no different than yours or mine.
And this will get into biotechnology
where we're actually
able to use these cells
to manufacture human proteins.
We'll show how we can actually
take prokaryotic cells,
splice a human gene into them,
and turn it into, say, human insulin,
or human growth hormone,
or vaccines, or things of that sort.
So due to the similarities
and exact nature
of how we manipulate and work with our DNA
and transcribe it and translate it,
you'll see how that becomes
really important later on.
Now, for you and I,
we don't have a big, large
circular piece of DNA,
we have linear pieces of DNA,
which we call chromosomes.
The smallest chromosome
that you and I have
is about 30 million nucleotides long.
Some of the longer chromosomes
are somewhere around hundreds of millions
of nucleotides long.
So in every cell in your body,
you have about five billion nucleotides.
That's quite a bit of genetic information.
However, scientists are
still trying to figure out
what a lot of that does.
There is, 98% of our DNA
doesn't encode genes.
Now it doesn't mean that
it's called junk DNA
as it has been referred to in the past,
but we're still trying to figure out
what a lot of it does.
We know that there are
certain elements within it
that are necessary for proper
navigation through our DNA,
but when you really look at it,
only 2% of our DNA actually
encodes what we call a gene.
You've heard of this before,
but let's really define what a gene is.
A gene is a sequence of
nucleotides that encodes protein.
So what happens is, you have your DNA,
there's a sequence of base pairs,
As, Ts, Cs, and Gs, that we call a gene.
It first gets copied into RNA,
and then that RNA gets
translated into the protein.
So really, a gene is
the genetic information
that tells the cell how to make a protein.
Now, we used to think that we had
a lot more genes than we actually do,
and the reason for that
is because when they looked at a cell,
they saw that there were
hundreds of thousands
of different proteins that were made.
Now, we knew that we didn't have
hundreds of thousands of genes,
but since the year 2000, so
in the last 15 years or so,
we used to think we had 60,000 genes.
Now, we know we have somewhere
between 20 to 25,000 genes.
So it's actually gone down
by 1/3 in our estimate.
We still are not quite sure.
One of the biggest problems is we have
some remnants of copied genes
that we call pseudo-genes,
and it's hard to tell whether or not
we actually use those or whatnot,
so that's why we have this range.
We're still not quite sure.
Remember, I told you,
early stages of genetics.
Now, of those 20 up to 25,000 genes,
we can actually make 20
times the number of proteins,
and you'll learn today
exactly why that's the case.
But that only accounts for
about 2% of your genome.
So there's 98% of your genome
that's used to regulate how
those genes are accessed,
it protects your DNA
and so on and so forth.
Now, here's the core of this lecture.
In the nucleus, the DNA stays.
To be protected from a
lot of different factors.
Remember, the DNA is the
blueprint that the cell needs
to essentially make everything
that it needs to function.
That DNA needs to be highly regulated,
and that's what the
nuclear envelope's job is,
you remember, back from
cell biology lecture.
It has these pores that
regulate what comes in and out.
So the DNA really never
leaves the nucleus.
So how do we get the
information from the nucleus
out to where you can actually
do something with it.
Well, that's where one
of these first processes
we're gonna talk about called
transcription comes into play.
Remember, transcription
is a copying process.
So what happens is DNA, a
part of it will be opened up
and copied into what we call
complementary nucleotides.
So the RNA will literary
be a copy of the DNA.
Now then the RNA leaves the nucleus.
So transcription occurs
here in the nucleus,
the DNA stays where it's at,
that copy now leaves the nucleus
and goes to where the ribosomes are at.
Now, remember, there's multiple places
where the ribosomes can be found.
They could be free
ribosomes in the cytoplasm,
or they can be found in the rough ER.
Now, the ribosomes are the organelles
that manufacture the proteins,
and this is what you're gonna see today
and how that's done.
Essentially, the ribosome
reads the nucleotides,
the sequence of nucleotides,
and translates that into
a sequence of amino acids.
So that's the translation process,
is that the ribosome will literally read
the coding sequence and interpret it
to know what order to put
the protein amino acids in.
Now, if you remember from what we learned
from organic chemistry,
the proteins, the sequence of amino acids
predetermines how the
protein's going to fold
into that tertiary structure,
or maybe it's gonna combine with others
and form a quaternary structure.
Either way, that order of the amino acids
predetermines the function of the protein.
If you don't get that order right,
you don't make the protein right.
Here's an analogy.
Let's say you have a
cookbook, that's your DNA.
That essentially makes every
protein that a cell ever needs.
Well, you don't need all
the information all at once.
Today, you just wanna make brownies.
So you don't want your kids
to mess up your core brownie recipe.
So you don't let them have
access to that cookbook.
Instead, you photocopy the
recipe of that, those brownies.
Then, you put your
cookbook back in the shelf,
it's safe and secure.
Then you can have this.
Now, if your child messes
this up a little bit,
you could just make another copy
of whatever the case may be.
I just don't let my kids cook with me.
So ultimately, the RNA
is kind of that copy,
that recipe that the cell needs
in order to be able to make the protein,
in this case, the brownies.
Now, your amino acids
are all the ingredients.
These are the things that go into this.
The recipe tells you what
order to put these in.
Good cook knows that there
is a particular order
in how things have to go in
and get mixed together and whatnot.
Now, if you do it correctly,
then every time you follow that recipe,
you're gonna get what you desire.
The right protein, good brownies.
However, let's say, in
the middle of the night,
her son goes in and says, "I'm
gonna screw with you, dad,"
and changes some of the recipes.
Instead of a teaspoon of salt,
he puts in a cup of salt.
Now, the cell, when it reads
the genetic information,
doesn't know what it was,
it just knows what it is.
So if something gets
changed here and copied,
then it's kind of like, well,
I guess it's a cup of salt.
And when you do that, every
time you follow that recipe,
you're gonna screw up your brownies.
Now, the same principle applies to DNA.
When the genetic
information gets messed up,
we call that a mutation,
then what happens is when it gets copied,
that mistake is copied.
And when it tries to assemble
the protein properly,
it makes mistakes in the protein assembly,
and this is the fundamental basis
for most genetic disorders,
is inherited mutations from
one generation to the next,
where we don't make our proteins properly.
And so you'll see the relationship here
between DNA and RNA proteins.
Now, let's talk about the
passing on of genetics
before we get into that overall process.
When a cell divides, as your
cells are constantly doing,
you have what we call adult stem cells
and all of your organs that
are constantly replicating
to regenerate your tissues.
That's really one of the reasons why
when you get into old age,
your skin starts getting wrinkly,
and your organs start failing,
is because these cells wear out
and stop regenerating your tissues,
as well as they did when
you were a lot younger.
So this process of cell division,
which you're gonna go into more detail
later on in lecture 12,
before cell can divide,
it first must duplicate all
of its genetic information.
Now, we all come from a
single cell, the zygote,
when the sperm fertilizes the egg,
we have 46 chromosomes.
What will happen is, as
we develop as a fetus,
the cell will keep dividing,
but before it can divide,
it has to duplicate all
of the genetic material.
So that when the cell divides into two,
then each cell gets that exact
same copy of genetic material.
This is one of the reasons why
no matter where you look
anywhere on your body,
you're gonna have the exact
same genetic information.
You take a skin sample,
you take a blood sample,
you take a sample of hair cells,
they're all gonna have the
exact same genetics in them.
Now, they don't use the
genetics exactly the same,
and that's why they behave differently,
but they all have the same genetics.
This is where DNA
fingerprinting comes into play.
In the next lecture, we'll show
how it doesn't matter if
you've got a blood sample,
you don't have to get
blood sample from somebody,
you can take a cheek swab.
Or you can take cells from
any part of their body
and match it up to that exact same DNA.
Now, how does it do this?
This is one of the first
processes I'm gonna test you on.
It's called semiconservative
DNA replication.
Your semiconservative DNA replication.
Now, before I go through this process,
I wanna make clear that
this process is very complex
and uses an army, and I
literally mean army, of enzymes.
Not just a brigade, not
a little group, an army.
But there's only three main ones
that are critical that you have to know.
So those are the three
that I'm gonna test you on, obviously.
You'll see others in the video I show you,
you'll see others in
some of these pictures,
but there are only three
that I'm gonna test you on.
Now, DNA is double stranded.
Remember, it is held
together by hydrogen bonds.
So in order to copy the DNA,
the first thing that has to happen
is the DNA has to be pulled apart.
This comes, here comes
the first enzyme called
DNA
helicase.
If you think of the word helix,
like the double helix,
DNA helicase essentially unwinds the DNA.
That's its job.
So it comes in and pretty much
breaks the hydrogen bonds,
splitting the DNA into
two separate strands.
So that's one of the first
steps that has to happen.
The next step is called,
or is accomplished by the
enzyme DNA polymerase.
Now, this is one of the
more critical enzymes
in this process.
Now, if you think of the word polymer,
remember we talked about
dehydration synthesis
and how monomers are
assembled into polymers,
that's what this enzyme does.
It literally comes in,
reads the template DNA,
and adds one nucleotide at a time.
So it literally covalently
bonds the nucleotides
in their phosphate sugars,
and will create the new
half of the DNA strand.
So if you see, if it comes in here,
and let's say, on this
one template actually,
we do this.
So remember, our base pairing rules.
What will happen is it will
break the strand in half,
that's the helicase.
Then the polymerase comes in here
and says okay, I see an A, I put a T.
I see a T, I put an A.
I see a G, or a C, I put a G, G, C.
On the other side,
another polymerase is
doing the same thing.
It sees a T, it puts an A.
It sees an A, puts a T.
It sees a G, puts a C.
It sees a C, put a G.
What do you notice about both of them?
They're exactly the same.
Because of this process,
what happens is, what
once was one DNA strand
now becomes two copies
of the original strand.
And that's why DNA needs
to be double stranded,
and that's one of the critical
things in its duplication,
is it splits into two templates.
The polymerase comes
along, reads both of them,
and adds nucleotides
in the growing strand.
So that's why it's called polymerase,
is because it builds the new polymer.
It adds one nucleotide at a time,
connects them together
and forms a long string
that will become the
second half of the new DNA.
Now, the reason why it's
called semiconservative
is because notice that each DNA strand
conserves half of what we
call the parent strand.
So here, what's in black,
that's half of the parent strand,
it conserves half of that in the new DNA,
and then it just uses those as templates
to create the other half of the new DNA.
Now, there's a problem with this process.
DNA, like any language, can
only be read in one direction.
So what ends up happening is,
when you, when the helicase comes in here
and unwinds the DNA,
and the polymerase comes in
and starts following that
and synthesizing the new polymer,
that's fine on this strand.
But on this strand, the polymerase
actually has to go in the other direction.
So as the helicase is unwinding it,
a new polymerase has to jump on
and then go back towards
where the other one started.
So it ends up creating these
broken fragments of polymers.
Now, here's the key thing.
Remember, we talked about how
enzymes only have one job.
Polymerase can only add
one nucleotide at a time.
When it reaches the other
broken polymer here,
it can't finish that last connection off.
And that's where the last enzyme
you have to know comes into play.
It's called DNA ligase.
Now, this one doesn't really
have a good mnemonic to it,
so you just have to remember it.
So DNA ligase.
It ligates or connects
those broken polymers.
It finishes that last covalent bond
that will connect the phosphate sugar
between these two polymers.
Now, this happens on both sides.
In this direction, it
occurs on this strand,
in this direction,
because it goes both ways,
helicase unwinds DNA
in this direction, too,
you have the same problem on this half.
So both sides are having this issue
with having to reconnect
the broken polymers.
So we illustrate that
just so you can kinda see.
So here, we'll show helicase
going in both direction.
So the helicase is
unwinding in this direction,
it's unwinding in that direction.
The polymer up here, we do this in green.
Polymer up here, the polymerase
goes in this direction.
Well, it has to come back here,
and then come back here,
so you can see that you
get these broken polymers.
Same thing here.
You had one start going this direction,
but then as this opens up,
it's gotta keep going back towards here.
So what ends up happening is,
you get these fragments that
need to be connected together.
So that's where the ligase comes in,
and we'll basically finish
that last covalent bond off between those.
So that in the end,
when all this is said and done,
you're gonna have two new DNA strands
that are carbon copies of each other,
unbroken, and these would be
the two new double helixes.
Then, during the process of cell division,
these two get separated from one another,
one goes into one cell,
the other goes into the other cell.
That's semiconservative DNA replication.
Let me show you a video.
It'll illustrate this process
as well as the base pairing rules
and such that we've gone over.
Now, let's look at a little,
some of the differences
between DNA and RNA.
DNA, as we know, is
the hereditary material
that gets passed on from
one generation to the next.
RNA, on the other hand, is transient.
As we've talked about
when you make that copy,
you can just throw that copy away
and make another copy later on.
And that's what the cell does.
It makes the RNA,
recycles the nucleotides,
and remakes a new RNA.
So RNA is constantly
being made and recycled.
Now, here are some of the
fundamental differences
between DNA and RNA.
They both use slightly different sugars
in their nucleotides,
and that's where they get their name from.
The RNA uses what we call ribose sugar,
and that's RNA, ribose nucleic acid.
DNA uses deoxyribose sugar.
The only difference is in oxygen.
They're almost identical in that regard.
But that's where they get their name from,
deoxyribose nucleic acid,
ribose nucleic acid.
Now, here's a big difference,
and this will be critical.
This is where you're gonna have
at least another test question.
DNA only uses As, Ts, Cs, and Gs.
RNA, on the other hand,
uses As, Us, Cs, and Gs.
So there's a fundamental
difference in this nucleotide here,
in that thymines are the nucleotide,
or the base in the nucleotides
that is exclusive to DNA,
and uracil is its replacement.
It doesn't have thymine
and RNA nucleotides,
it uses uracil.
They are almost exactly the same.
There's just a slight methyl
group difference between them.
And in fact, the base
pairing rules are the same.
So whereas before, you
have A with T, C with G,
now you have A with U, C with G.
So the base pairing rules
are pretty much the same.
The only difference is, RNA uses uracil,
and DNA uses thymine.
Now, how does that work when
DNA gets copied into RNA?
'Cause this is what I'll test you on.
So let's say that the DNA strand,
let's do Gattaca again, that's a fun one.
Now, let's say that this is the DNA.
And that this is the template
that's being copied into RNA.
What would the RNA copy then look like?
C, U, because remember,
it doesn't have thymines.
It only has uracil,
but the base pairing rules are the same.
Now, if it sees a T,
it doesn't get confused,
what's it gonna put over here?
An A.
'Cause there are adenines and RNA.
U, G, U.
That's what the RNA would look like.
So the RNA uses As, Us, Cs, and Gs.
This is gonna be another type of question
I'll test you on where I may say,
here's the DNA template,
what's the RNA strand
that's copied from that DNA,
and you'll have to remember
that fundamental difference
between DNA and RNA.
As with Us, Gs with Cs, same thing there.
So wherever in the RNA would
have a T, it has a uracil.
RNA also is single stranded,
it's never double stranded.
Because when it's double stranded,
the cell actually chews it up.
It needs to be single stranded
to be able to be accessible.
Even DNA can't be read
unless you rip it apart
and turn it into a single strand,
like we see with there whatnot.
So though DNA is double stranded,
for stability reasons
and whatnot, and copying,
RNA has to be single stranded
for it to be accessible
as far as the information goes.
So (indistinct) some of the fundamentals
between DNA and RNA.
Now, there are multiple types of RNA.
And we're only gonna
talk about three of them.
These are the three critical RNAs
that are found to be
necessary to make a protein.
So of this three RNAs, they each vary
in their responsibility and their function
in the process of making a protein.
So you're gonna have to know
what each of those functions are.
All right, let's start with mRNA.
What does the m stands for?
Stands for messenger.
This is the RNA which
holds the information
that the cell needs to make a protein.
Meaning, when we copy DNA,
when we copy a gene,
that's the messenger RNA.
So when a gene is copied,
when that sequence that tells the ribosome
what order to put the
amino acids in is copied,
that's the messenger RNA.
Now, the messenger RNA is gonna
be different for every gene.
We have 20 to 25,000 genes,
the RNAs are gonna be different
depending upon what gene is being copied.
So the messenger RNA
ultimately is that blueprint
that the cell needs to make the protein
to put the amino acids in the right order.
Now, rRNA and tRNA are
more for the mechanics.
These are universal for any protein.
They're not specific for any one protein,
they're more of the complementary RNAs
that help the ribosome
to make the protein.
So rRNA actually stands for ribosomal RNA.
Back when we learn about organelles,
we talked about how organelles
are made up different biological groups.
Well, guess what?
A ribosome, which is the
organelle that makes proteins,
is not pure protein.
It's actually a combination
of ribosomal RNA,
or this nucleic acid, and protein.
So these two biological molecules
ultimately make up the ribosome.
But that's all rRNA is,
is a structural component
with the proteins
that ultimately create the
organelle, the ribosome.
So these rRNAs do vary as well,
but not, they don't vary per protein,
there's just a couple
different versions of rRNA.
All you need to know is it makes up
the ribosome with the protein.
So that's ribosomal RNA.
Now, this is also copied from DNA,
but doesn't necessarily have
its own gene, so to speak.
So there is a segment of
DNA that copies the rRNA,
but it's like mud and tape in a wall.
It doesn't matter what
else you do with it,
it's just structural.
Now, these are critical.
tRNAs.
We call them transfer RNAs.
These are some of the smallest RNAs,
and they play a key role
in the translation process.
Now, the T doesn't stand for translation,
it stands for transfer,
but if you wanna think about it
in that term as well, you can.
What's critical about the tRNA
is that they bring the amino acids
to the ribosome so that the
ribosome can create the protein.
So the transfer RNAs,
the reason why they're
called transfer RNAs,
is 'cause they transfer the
amino acids to the ribosome.
Now, we'll talk a little bit
more about how they function,
'cause it's a little
more complex than that
when they bring the amino acid,
but those are the fundamentals for now.
So the same principle applies here
for RNA transcription.
Now, when we talked about
semiconservative DNA replication,
this is no more than
saying DNA transcription.
So DNA transcription is
when you copy DNA to DNA.
RNA transcription is
when you copy DNA to RNA.
Make sure you know that difference.
That will show up on the quiz questions.
For example, if I gave you
that sequence, Gattaca, again,
and I say, which is the
complementary sequence
that's created through RNA transcription,
then I'm looking for the
complementary RNA from that.
If I ask you what's the
complementary DNA sequence
through DNA transcription,
I'm looking for the DNA copy
that's done during
semiconservative DNA replication.
So do make sure you understand
the difference between those two.
Now, here's another fundamental
difference between the two.
When RNA gets transcribed,
you don't copy all of the DNA.
Remember the cookbook scenario.
I just wanna make brownies today.
I don't wanna make anything else.
So I don't need to copy every page.
I just copy the page I need.
So that's RNA transcription,
is you only copy the segment of DNA
that you wanna make a protein of.
So the portion of DNA that
you need gets opened up,
the RNA polymerase, which
only uses RNA nucleotides,
will come in and do the same thing
that the DNA polymerase did.
It'll read the DNA,
but instead of using DNA
nucleotides as the building blocks,
it uses RNA nucleotides
as the building blocks.
Again, it's C, U, A, A, U, G, U.
That will be the complimentary nucleotides
that the RNA polymerase
copies from the DNA template.
Now, when it's done, the
DNA gets closed back up,
and now you have your messenger RNA.
This is the one that has the template
that the ribosome needs to
be able to make the protein.
All right, now, here is where
we talk about the question.
If we have only 20 to 25,000 genes,
how do we make hundreds of
thousands of different proteins?
How do you make more proteins
than you have templates for?
Yeah?
- Sorry, quick question,
going back to what you should
have said in simple term,
pretty much DNA opens up, RNA comes in,
copies, and then pulls back
away, and DNA closes in again,
and that's when the RNA
is just a single strand.
- [Instructor] Yep, yeap, yeah.
so it's doesn't pull the DNA apart,
copy full sets and all that kind of stuff.
It just copies 1/2 of it,
and you just create the
single stranded RNA.
Yeah.
So here is the key.
Imagine that, you don't
wanna have a recipe
for every possible cookie
variation there is.
You've got chocolate chip cookies,
maybe you wanna add
peanuts or peanut butter,
peanut butter, peanut chips to it.
Maybe you add white chocolate chips,
but the basic recipe of
the cookie is the same.
And that's the same thing here.
Some proteins have slight variations
that can be modified from
the original template.
So in fact, the genes say, well,
here's the information to make
10 different types of proteins.
It's all a matter of how you splice it.
And that's really what happens in here,
is once the RNA is made,
the cell knows how to remove
certain sections and say,
ah, I don't want white chocolates,
I'm just gonna have regular
milk chocolate chips in my cookies today.
And another day, another cells like,
ah, I want both,
I want white and chocolate
chips and the others.
Getting hungry now, all
right, so ultimately,
that's how you can take 20,000 templates
and make 400,000 different proteins
is through what we call splicing.
So literally remove sections of the RNA
and only that which gets spliced out
and then left behind,
which is, don't worry
about introns, exons,
it's not necessary, it's
not even gonna show up.
The only word that you're
gonna have to know is splicing.
So RNA splicing is the reason
why we can make more proteins
than we actually have templates for.
So now, here comes the key.
Literally.
What is the genetic code.
How do these sequence of nucleotides
actually make any sense to the cell
or to the ribosomes that are
trying to put it together.
Well, you know that binary code
is a series of zeros and ones,
and that encodes information,
depend upon the order of those.
Well, this is actually
more complex than binary,
more involved.
These four nucleotides,
when they're sequentially arranged,
form triplet code words called codons.
So every three nucleotides
is what we call a codon.
And there are multiple versions
or variations of these.
Let's see if you, for those of you
who may know a little bit of math,
if we've got six possible nucleotides,
let's make this easy to use
because we're doing RNA here,
if we have four possible nucleotides
with three possible spaces,
how many variations are there,
how many permutations are there?
How many?
There are 64 possible codons.
Now, here's a secret.
What does a codon mean?
A codon encodes an amino acid.
One codon literally means
a particular amino acid.
Now, do you remember,
how many amino acids are there?
Remember, yeah?
There are 20 amino acids in total.
But there are 64 possible codons.
So you're like, okay, well,
here's what it looks like.
There are what we call synonymous codons.
Now, in English, what's a synonym?
Different words that what?
- Means the same.
- Mean the same thing.
Synonymous codons are codons
that are different in
their three nucleotides,
but they mean the same amino acid.
Now, some, there's a lot,
like for example, leucine
has six anonymous codons.
Proline has four, histidine has two.
So it varies.
But here's the fascinating thing.
Every cell on the planet
uses this exact same coding sequence.
There is no variation from
one species to the next.
Everything uses this coding sequence,
down to the last nucleotides.
Now, some codons don't
have synonymous codons.
In fact, this one right here,
which is one of the more
critical codons, the AUG,
that's what starts all protein synthesis.
So don't worry about
memorizing any of these codons,
the relationship between the
amino acids and the codons,
but you do have to understand
what synonymous codons are.
That comes up in a concept
that I will test you on.
So there are more codons
than there are amino acids,
which means there are
these synonymous codons.
Now this will become important later on,
you'll see how this actually protects us
from being more messed
up than we actually are.
Because when mutations occur,
and they change this nucleotide,
it still means the same thing.
And we see that over and over again,
where people may have slightly
different genetic codes,
but they make the
proteins exactly the same.
And this is one of those
protective measures
that we have in our DNA to
prevent problems that occur.
Instead of, your child comes in
and thinks that he's
messing up your recipe,
and he says, oh, two
half teaspoons of salt,
when it's a teaspoon of salt.
You're like, well, I get the same result.
That's kind of how it works,
is something gets messed up,
but it still means the same thing,
you still get the same end result.
All right, now, here's
how translation occurs.
The tRNAs, which have
the amino acids on them
also have a three coding sequence
on their strand called the anticodon.
Well, all the anticodon is
is the complementary nucleotides
to the codon on the messenger RNA.
For example, AUG is the codon.
What would be the anticodon for that?
Starting from left to right.
UAC.
So there's a tRNA with the
anticodon UAC on one end,
and on the other end, it has methionine.
Over here, we've got the
codon, CCC, for proline.
So there's a tRNA that has
the anticodon, what, GGG.
So it has the GGG anticodon,
which is the complementary pair here,
and on the other end, it has a proline.
That's where tRNAs play
their critical role.
It's because the messenger RNA
carries the sequence of codons,
and as the ribosome
reads the messenger RNA,
it puts the tRNAs associated
with their proper codons,
'cause they've got the anticodon for that,
in that order, and then starts
putting the amino acids together.
So let's see how that works.
Now, the ribosome is this
large protein rRNA complex
that basically has two sites in it.
And so only two tRNAs
can come in at a time.
Well, that's fine.
That's how it works.
Because it will take the two tRNAs,
it will covalently bond
the amino acids together
through dehydration synthesis,
and then it'll shift down one,
and then do the next one.
So here's how it happens.
Methionine is always the first one.
The AUG literally is,
like we know that when
we're doing a sentence
like the animals, blah
blah blah blah blah blah.
We know what the beginning
of the sentence is
because it's got a capital letter.
But we know what the beginning
of the sequence of proteins are
because it's AUG, that's
the universal start site
for any protein in any organism.
Now, when the tRNA or
the ribosome comes in,
it now has tow slots.
The first one's always gonna be fitted
by the tRNA with the methionine.
And then it looks for the next one.
Okay, so it's GGA, it'll bring in CCU.
That's the only tRNA
that will fit in there.
All others that try to come in
just bounce right back out.
So only the tRNA with the
complementary nucleotide sequence,
the anticodon, can fit in here.
Then it covalently bonds
these two amino acids.
The ribosome shifts down one spot,
and that tRNA will go and be like,
ah, I need to go get another methionine.
So it'll go from the stockpile, the cell,
grab another methionine and come back
to be a part of this process.
Well, as the ribosome shifts down one,
the next tRNA comes in.
It covalently bonds amino acids.
Shifts down one, the next
one, and so on and so forth,
until it finally reaches
what we call a stop codon.
Now, this is critical as well.
Stop codons are the only codons
that don't encode an amino acid.
I'll show you how I'm
gonna test you on this here
in a second after I show you the video,
but they don't encode an amino acid,
they're the only ones that don't.
The start codon does.
And all the other codons do,
but when you finish,
it's kind of like the period, at the end.
It's not a letter, it's not,
it doesn't mean anything,
it just says, you're done.
So all proteins have a
beginning, a middle, and an end,
all codons mean amino acids,
one-to-one relationship,
except for the stop codon,
will stop the growing
chain and say you're done.
You're done making the protein.
Now, these RNAs don't
just do a one-to-one.
You don't have one ribosome copy, one RNA.
In fact, it forms an assembly line.
A single RNA can be copied
over and over and over
and over and over again.
So it literally is an
amplification process.
One mRNA could be copied
thousands of times,
because the protein
needs to make thousands
or hundreds of thousands of proteins.
So this just shows electron
scanning micrograph
in pseudo-colors, so you
can see the ribosomes here,
and you can see these
strings of amino acids
that will result from that,
just kind of forms this assembly line.
Once one latches on
and starts moving down,
another can latch on and move
down and so on and so forth.
So it's just like putting a paper
in the Xerox machine and pressing 1,000,
it copies it over and over and over again.
Well, here is the problem.
And I mention this in the beginning.
That order of amino acids is critical
for the proteins function.
If it doesn't get folded properly,
then it doesn't have its proper function.
So if you mess up even one amino acid
due to what we call a mutation,
then the protein doesn't
get made properly.
So let's look at some mutations.
There are two types of mutations
that I'm gonna test you on.
The first type of mutation
is called a point mutation.
Now, when we say point mutation,
we mean a substitution for nucleotide.
So here's an example.
When your DNA gets copied,
or when you're exposed to X-rays,
or even just constant
exposure to UV radiation,
your DNA gets damaged.
Your cells, to regenerate and to renew it,
kind of pull out a piece of the DNA
and then recopy it.
Well, every time you have to recopy
that portion or repair your DNA,
every once in a while,
makes some mistakes.
It doesn't make those mistakes
very often, but it does.
The more you're exposed
to what we call mutagens,
eating Twinkies or going out
in the sun light, or whatever,
there's lots of things
that can mutate your DNA.
So here's an example.
Remember we talked about that recipe book.
And if you changed it
from a teaspoon of salt
to a cup of salt every time you copied it,
you're screwing up your brownies.
Well, here's an example.
Here's the DNA, there's
the copy of the RNA,
and there is a sequence of amino acids
that are associated with the codons.
Well, let's say we come in here
and exchange this T for an A.
Now, when the RNA is made,
instead of this codon being GAG,
it's gotta be the codon GUG.
Well, that encodes a different amino acid.
And instead of having it
proline, glutamate, glutamate,
it's proline, valine, glutamate.
This is one of the causes
of sickle cell anemia.
A single change in the nucleotide
causes the hemoglobin in your
red blood cells to collapse.
And the cells form the sickle shape
and they can't carry
oxygen, hence the anemia.
So a single change in a
nucleotide can screw up
how the protein gets folded
and cause these genetic
disorders, like cystic fibrosis
and cycle cell anemia, and
Tay-Sachs disease and the like.
So that's a point mutation,
is when you change a nucleotide on the DNA
and it ultimately can cause
a different amino acid.
Now, that's not as bad as
you might think, actually.
Why?
Because, come back to here,
what if the point mutation
occurs right here?
Will anything happen?
What if it occurs on the
third nucleotide on the DNA?
And instead of CCU, the
codon now becomes CCC?
It won't change the amino acid.
So this is why I told you
that because we have synonymous codons,
there's some protection there.
You can accidentally get a point mutation,
but if it's in that spot
where you have a synonymous codon,
then nothing happens.
Because the same amino acids
are put in the same order,
no problems whatsoever.
All right, so the second type of mutation
that we're gonna talk about is
called a frameshift mutation.
So frameshift is when the reading frame
of the nucleotide
sequence shifts down one.
Now, there's a couple ways
which this can come about.
Usually, it comes about
through either an insertion
or a deletion of nucleotides.
So let me pull up the
counterpoint here real quick.
So here's an example of a frameshift.
You've got the original
DNA sequence up above,
and if you add a nucleotide,
say this T right here, what happens is,
remember that the ribosome
can only read every three
nucleotides, every codon.
And if you add one, then it shifts
that reading frame down one,
so that all of these codons
are gonna be different.
To illustrate how this works,
love dogs, hate cats,
so if you have like a point mutation,
that's where you substitute
one letter for the other,
but look, it doesn't really
affect anything else.
You get the same sentence,
same meaning or whatnot.
So it all depends upon
where that substitution is.
But let's say you add a
letter, add a nucleotide.
Well, it doesn't all of a sudden do this.
Remember, it only reads at every three.
So it shifts everything down.
And now it doesn't make sense.
And the same thing is
true for this frameshift.
So a frameshift mutation
is when you have an addition or deletion,
you can actually take nucleotides away,
they get mistakenly taken out,
and it shifts the reading frame.
And you pretty much screw it up.
There's not really anything
coming back from that one.
