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HAZEL SIVE: Welcome back to Getting Up to Speed in Biology.
By now, you have had a lot of basic information
that should be getting you ready to take introductory biology
at MIT or elsewhere.
You should have completed your first problem set
in addition to all the class exercises that we've given you.
So you're on pretty good ground now
to move on to the last two lecture units.
Today's lecture, today's class, is
going to be about how changes in DNA, changes in genes,
govern the outcome for the organism.
We're going to talk about mutations.
We're going to talk about alleles.
We're going to talk about pedigrees.
And if you don't know what those words mean,
you're in the right place.
Here are our topics for today.
We'll firstly talk about mutations.
We'll talk about something I'll term allele segregation.
We'll talk about genetics and genetic crosses.
And finally, we'll talk about pedigrees.
The overall theme of today is, how does a DNA sequence
connect with a trait?
A trait is something you can see,
an observable characteristic-- your eye color, your hair
color, for example, also called a phenotype.
DNA sequence may alter the protein that's made,
the amount or the type of protein,
and may change all sorts of things, including
whether a dog is big or little or whether an insect has
got normal mouth parts or has got legs
growing out of its head.
Let's begin by talking about mutations.
Let me start by reminding you what
we talked about last time-- the information flow from DNA
to protein to a trait.
DNA, the gene, is transcribed into RNA, which is then
translated into protein.
This is the information flow we talked about yesterday.
That protein then has a function that
may give an observable characteristic which
we call a trait.
Let's write that down.
A trait is something you can see,
an observable characteristic.
And the scientific term for that is phenotype.
If you change the DNA, you may change the RNA,
and you may change the protein, and you may change the trait.
These DNA changes occur in the bases.
So DNA base sequence changes are called mutations,
and they are relative to something
else, whether you have a mutated gene or not.
More usually, we think about genes
that have got different variants of sequence.
We'll come to that in a moment.
But mutations may alter protein sequence
and may alter protein function, and therefore,
may change a trait.
That's your general notion of mutations.
There are really two classes that I want you to know about,
two types of mutation.
The first are point mutations.
These change one base at a time.
They change one base, and they substitute another base
at the same position in the DNA sequence.
The second type that I want you to know about
are the insertions and deletions.
Insertions add one or more bases,
and deletions remove one or more bases.
There's also a whole other class of mutations
that affect something other than the actual protein coding
sequence.
And we'll talk about those very briefly in a moment.
But let's look at some slides here
so we can get a sense of how you might change protein
sequence by changing the DNA.
I've shown you here on this slide a double-stranded piece
of DNA.
You see all the polarity that you know now
and the base pairing.
The bottom strand I've designated
as the template strand.
And I've shown you the messenger RNA
that is transcribed using that bottom strand as a template.
And then I've shown you the protein
that is translated from the codons of that messenger RNA.
I've designated this the wild type gene.
It's a reference point.
Wild type-- sometimes people use the term "normal,"
but that's not correct.
It's usually the most common version of that gene.
OK.
Let's see what happens now if we change that gene.
So on top, again, I've got what I
had on the previous slide, the wild type gene and protein.
And now we've made a point mutation
where we've changed a single base in the DNA.
It's underlined in pink.
We've changed it so that instead of reading--
what was it?
It was GGA previously.
It now reads GGT.
You can look at it the same time I do.
So we've changed there an A to a T.
And on the other strand, that also flips the base,
changes it from a T to an A. The messenger RNA is now
changed because the template for the messenger RNA has changed.
And when that messenger RNA is translated into protein,
you can see that there is now a different amino acid
in the protein chain.
There is a valine instead of an asparagine or aspartic acid,
the valine instead of aspartic acid.
OK?
So the protein sequence, the actual sequence
of amino acids in the protein, has changed.
This type of mutation is a point mutation, as I said,
and it's called a missense mutation.
You get a protein, but it's a bit different.
Here's another kind where, again, you make a single base
change in the DNA.
It's underlined.
And then if you start your protein translation
from the RNA that is made using this now-new template,
you see that immediately after the first amino acid,
methionine, there is a stop codon that stops translation.
And the protein isn't made at all
except for that first amino acid.
This is called a nonsense mutation,
and it truncates or prematurely stops the protein.
And obviously, you wouldn't get a functional protein here.
In the case of the missense protein,
it might be functional, but it might have a slightly different
function than the starting one.
Here's another example of a point mutation,
and this one's going to be a silent mutation.
In this case, there has again been a base substitution
so that the DNA template changes.
But now, if one makes the messenger RNA conceptually
and the protein, you see that the protein
sequence of the mutated gene is the same as the parental gene.
And that's because more than one codon
can code for the same amino acid,
as we saw previously when we looked at the genetic code.
So although the DNA has changed, the protein hasn't changed.
And this is called a silent mutation.
Here's an example of an insertion.
The arrow indicates where a base has been inserted
in the DNA that wasn't there.
And this does something profound to the protein.
It changes something called the reading frame.
You recall that proteins start with ATG AUG as the RNA codon,
and that corresponds to methionine.
And then you read the RNA with no spaces.
We explored that in the previous class.
You read three by three right next to each other.
And that sets the reading frame.
It tells you what the protein codons
are going to look like one after the other.
If you add anything other than a multiple of three bases,
you change the reading frame.
Here I've put in one, one extra base.
And look what happens to the protein coding sequence.
You now see you start the same, the thiamine tryptophan.
But now, instead of having leucine, proline, aspartic
acid, you now have threonine, proline, lysine, and so on.
OK?
So you've changed the reading frame and the protein that is
made from this particular gene.
And that might profoundly change the function of the protein.
It might make it non-functional.
It might sometimes give it a new function.
It might give it a function that causes disease.
So this is the insertion changing the reading frame,
and the same idea is true for a deletion
changing the reading frame.
So the last thing that I'll indicate here on the board
is that mutations can change protein coding sequence,
but they may also change the sequence of what
I'll call control regions--
control DNA, let's call it, where the control DNA is
actually dictating whether or not the RNA is
made in the first place.
And we didn't discuss this really at all
when we talked about transcription,
but I'm planting this notion in your mind
now so you will have heard of it--
this control DNA which regulates RNA synthesis, transcription.
And this can change the amount of the RNA
and the amount of the protein made.
Good.
You are empowered now to go to assignment 1, class exercise 1,
and practice your protein coding skills
and figure out what happens when you
make various mutations in DNA to the protein that is made.