great system for checks and balances making
sure that our DNA integrity is maintained.
Sometimes though things go a little bit arise.
What when all these mechanisms are bypassed
and we actually end up with a mutation in
a cell that is going to become a gamete and
that mutation gets passed on.
Let us look at some point mutations and following
that we will look at chromosomal mutations.
Point mutations involve one change or a very
small change in the local area on a strand
of DNA or in the chromosome whereas chromosomal
mutations are large scale changes in the structure
of chromosome. Our point mutations will visit
our friend, here again, hemoglobin. Previously
I have introduced you to sickle cell anemia
and its relationship to hemoglobin. You recall
hemoglobin has two alpha subunits and two
beta subunits that each has a slightly unique
folding pattern and create an active site
for the binding of oxygen. If the binding
site is messed up, it is not going to carry
oxygen or it is not going to fold in a proper
way to allow it to do its job properly. Let
us look at what has gone on specifically.
This sickle cell anemia results from a point
mutation, one nucleotide base change. Here
is our normal hemoglobin B gene and what it
results in coding in our amino acid sequence
and then when we have abnormal hemoglobin,
we can see a slight change, which results
in a changed amino acid. Here is the change.
We are just changing and A for a T, very,
very small change with a very profound effect.
We are changing from a polar amino acid to
a nonpolar or hydrophobic amino acid and that
presents some problems in protein foldings
such that the beta chains will have a different
folding arrangement so that they are very
sticky and don't stack up quite properly in
the red blood cells. So they will start to
form chains where the deoxygenated portion
of the beta subunit will fold in a little
bit and that will cause them to stick together
in these chains and when they end up inside
the red blood cell in this form, the oxygenated
form then they cause the cell to sickle. They
are okay when they are oxygenated, but hemoglobin
has to be oxygenated and deoxygenated. This
is why we only see the profound effects of
sickle cell anemia in lower oxygen environments
or during hard exercise because when there
is a lack of oxygen, it is less oxygenated
sickles and the cells will get stuck at places
and causes a platter of different effects.
That is an example of how a single point
mutation can have such a vast effect on gene
expression and the shape of final proteins.