Well, there’s yet one
more thing to understand
about hemoglobin that’s
And this is a disease known as sickle cell
anemia which most people have heard of.
Sickle cell anemia is a genetic disease
and it affects specifically hemoglobin.
There are multiple forms of sickle cell
anemia and result form different mutations,
but the most common mutation
occurs by changing a glutamic acid
at position number
six to a valine.
Now, that very minor change
in the structure of a protein
causes this hemoglobin to have
some very unusual properties.
The hemoglobin will tend in these
cells to have a polymeric form
when the oxygen
concentration is low.
This polymer of hemoglobin
causes the red blood cell
that contains it to
change its shape.
That shape change happens and causes
a sickle form of the blood cell
as a result of the polymerization of
the hemoglobin that I’ve described.
Now, you can see on this picture,
at the very top, sickled cells.
These are cells that have encountered
that low oxygen concentration.
They’ve had their
and the cell shape has
Well, sickled cells are
real problems in the body.
Because as the blood cells are
traveling through the body,
they have to pass
Capillaries are where most of the
oxygen exchange actually occurs.
Rounded red blood cells make it through
those capillaries very readily.
But the capillaries are where
the oxygen is being taken away.
It’s in those capillaries where the
oxygen concentration will be the lowest,
and it’s in those capillaries where the
sickling of the red blood cell will happen
in a person who has this disease.
When that happens, these sickle shapes
form, they block the capillaries.
The sickled cells get stuck
inside of the red blood cells.
Now, as you can imagine, this
is a pretty nasty thing.
First of all, the tissues that
contain those capillaries
are not getting the
oxygen that they need.
So a person who has sickle
cell anemia will have pain
that they will suffer from
whenever they exercise heavily
because their capillaries are not
delivering the oxygen that’s necessary
and moreover, they’re being plugged
up with these sickled cells.
The reason that this disease
is called “sickle cell anemia”
is that these sickled cells are recognized
by the spleen as being damaged.
And the spleen’s job is getting
rid of damaged blood cells.
So even though the cell might be okay
when the oxygen concentration
comes back to normal,
the hemoglobin has caused it to
look like the cell is sickled
and the spleen says that’s a bad cell
and takes it out of circulation.
So a person with sickle cell
anemia, they’re losing more cells
to destruction by their spleen than a
person who doesn’t have the disease.
And anemia, of course, is a decreased
concentration of blood cells.
So sickle cell anemia is a
very difficult problem.
Well, you might ask the question, “Why
is sickle cell anemia so widespread?
If it’s so deleterious, why
wasn’t it selected against?
Why do we still see it
in the population?”
And a lot of people wondering about
this question until a few years ago.
The question was answered when they
started looking at a world map
and comparing where the greatest incidents
of sickle cell anemia was found,
and they contrasted that with where the
greatest incidents of malaria was occurring.
Now, sickle cell anemia of course is
found all around the world today.
So I don’t mean to say it’s focused
only in Africa because that’s not true.
But the reality is, is that sickle cell
anemia appears to have given some advantage
to people who lived in
and survived it as a result
of surviving malaria.
This slide shows the genetics
involved in the survival of malaria
by people who carry one
of the sickle cell genes.
Now, to understand this, we
have to remember first of all
that we each have two
sets of chromosomes.
One set of chromosomes
can have one gene.
And the identical set of chromosomes
can have a different one.
That’s known as heterozygote.
So, for example, if I was a
carrier of sickle anemia,
one of my sets of chromosomes would have
a normal unmutated form of hemoglobin.
And the other set of my chromosomes
would have a mutated form.
That’s heterozygous, meaning
that they’re different
between the two
If I’m homozygous, that would
mean that both sets are the same.
So I could be homozygous
for the mutated form
which means both of my chromosomes
have the mutated form.
Or I could be homozygous
for the normal form,
the unmutated form in which case
both sets of my chromosomes
would have the unmutated form.
When they compare the
survival of people
who had been affected with malaria,
they found something interesting.
What they found was that people who were
heterozygous for the sickle cell gene,
one copy bad, one copy good,
were much more likely to
survive malaria as youths
than people who were homozygous for
the normal or for the defective.
There was something about
that heterozygous state
that protected the person
from dying of malaria.
This is the reason we think why sickle cell
anemia has persisted in the population.
There’s a benefit to
carrying one gene
if you’re living in an area that’s
highly infested with malaria.
There are no benefits on
either other side however.
In this presentation, we’ve
seen a lot about hemoglobin.
We’ve seen how hemoglobin
is able to deliver oxygen
according to the varying needs of the body
and how it response to
conditions with protons,
with carbon dioxide and with 2,3 BPG,
all things that
We’ve also seen how the fetal
hemoglobin is different
and allows the fetus to have the oxygen
that it needs and get that oxygen from mom.
And last, we’ve seen the actual advantage
of a mutated form of hemoglobin
to help people survive malaria.