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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.
