Evolution And History

The Case of Sickle-Cell Anemia 49

This example also points out that adaptation tends to

be specific; the abnormal hemoglobin was an adaptation

to the environment in which the malarial parasite flour-

ished. When individuals who had adapted to malarial re-

gions came to regions relatively free of malaria, what had

been an adaptive characteristic became an injurious one.

In environments without malaria, the abnormal hemoglo-

bin becomes comparatively disadvantageous. Although

the rates of the sickle-cell trait are still relatively high

among African Americans—about 9 percent show the

sickling trait—this represents a significant decline from

the approximately 22 percent who are estimated to have

shown the trait when African captives were shipped across

the Atlantic and sold as slaves. A further decline over the

next several generations is to be expected, as selection re-

laxes for the frequency of the sickle-cell allele.

This example also illustrates the important role cul-

ture may play even with respect to biological adaptation.

In Africa, the severe form of malaria was not a signifi-

cant problem until humans abandoned food foraging

for farming a few thousand years ago. In order to farm,

people had to clear areas of the natural forest cover. In

the forest, decaying vegetation on the forest floor made

the ground absorbent, so the heavy rain rapidly soaked

into the soil. But once stripped of its natural vegetation,

the soil lost this quality. Also, without the forest canopy

to break the force of the rainfall, strong rains compacted

the soil further. As a result, stagnant puddles commonly

caused by the death of those homozygous for it (from
sickle-cell anemia) was balanced out by the loss of alleles
for normal hemoglobin, as those homozygous for normal
hemoglobin were more likely to die from malaria and to
experience reproductive failure.
Expression of normal versus sickle hemoglobin in a
heterozygous individual represents an example of incom-
plete dominance. The mutation that causes hemoglobin to
sickle consists of a change in a single base of DNA, so it can
arise readily by chance (see Figure 2.7). The resulting mu-
tant allele codes for an amino acid substitution in the beta
chain of the hemoglobin protein that leads red blood cells
to take on a characteristic sickle shape. In homozygous
individuals with two sickle-hemoglobin alleles, collapse
and clumping of the abnormal red cells block the capil-
laries and create tissue damage—causing the symptoms
of sickle-cell disease. Afflicted individuals commonly die
before reaching adulthood.
The homozygous dominant condition (HbAHbA—
normal hemoglobin is known as hemoglobin A, not to be
confused with blood type A) produces only normal mol-
ecules of hemoglobin whereas the heterozygous condition
(HbAHbS) produces some percentage of normal and some
percentage of abnormal hemoglobin. Except under low
oxygen or other stressful conditions, such individuals suf-
fer no ill effects. The heterozygous condition can actually
improve individuals’ resilience to malaria relative to the
“normal” homozygous condition.

Figure 2.8 The allele that, in homozygotes, causes sickle-cell anemia makes heterozygotes
resistant to falciparum malaria. While falciparum malaria is also found is tropical Latin America, the
sickle cell allele is most common in populations native to regions of the Old World where this strain
of malaria originated.

Malarial areas

Sickle-cell anemia areas

Areas with both malaria

and sickle-cell anemia