Evolution And History

48 CHAPTER 2 | Genetics and Evolution

increased ability to survive the effects of the malarial para-

site; it seems that the effects of the abnormal hemoglobin

in limited amounts were less injurious than the effects of

the malarial parasite. Thus selection favored heterozy-

gous individuals with normal and sickling hemoglobin

(HbAHbS). The loss of alleles for abnormal hemoglobin

change shape (sickle) and clog the finest parts of the circu-
latory system, is caused by a mutation in the gene coding
for hemoglobin, the protein responsible for oxygen trans-
port. This disorder first came to the attention of geneticists
in Chicago when it was observed that most North Ameri-
cans who suffer from it are of African ancestry. Investiga-
tion traced the abnormality to populations that live in a
clearly defined belt across tropical Central Africa where
the sickle-cell allele is found at surprisingly high frequen-
cies. Geneticists were curious about why such a harmful
hereditary disability persisted in these populations.
According to the theory of natural selection, any alleles
that are harmful will tend to disappear from the group, be-
cause the individuals who are homozygous for the abnormal-
ity generally die—are “selected out”—before they are able to
reproduce. Why, then, had this seemingly harmful condition
remained in populations from tropical Central Africa?
The answer to this mystery began to emerge when it
was noticed that the areas with high rates of sickle-cell ane-
mia are also areas in which a particularly deadly form of
malaria (falciparum) is common (Figure 2.8). This severe
form of malaria causes many deaths or, in those who sur-
vive, high fever that significantly interferes with the victims’
reproductive abilities. Moreover, it was discovered that he-
moglobin abnormalities are also found in people living in
parts of the Arabian Peninsula, Greece, Algeria, Syria, and
India, all regions where malaria is (or was) common.
Further research established that while individuals
with hemoglobin abnormalities can still contract ma-
laria, hemoglobin abnormalities are associated with an

Normal Allele

Sickle Cell Allele

Codon

Amino acid

Position

CTG ACT CCT GAG GAG AAG TCT

Leucine Thr Proline Glutamic

acid

Glutamic

acid

Lysine Serine

3456789

Codon

Amino acid

CTG ACT CCT GTG GAG AAG TCT

Leucine Thr Proline Valine Glutamic acid Lysine Serine

Figure 2.7 Mutation of a single base of DNA can result in a dramatically different protein. Pictured
here are codons 3 through 9 for the beta chain of hemoglobin, the protein that carries oxygen in
red blood cells and the amino acids these codons specify. The top row depicts the normal allele,
and in the bottom row is the single substitution that makes the red blood cells bend into a sickle
shape (clogging the capillary beds and causing great pain, which is what occurs with sickle-cell
anemia). Sickling occurs because the amino acid valine, compared to glutamic acid in the normal
allele, gives the hemoglobin molecule different properties. The beta chain is 146 amino acids long.
A simple mutation (the substitution of thymine for adenine in position 6 as indicated in red) has
dramatic and tragic consequences.

sickle-cell anemia An inherited form of anemia caused by a

mutation in the hemoglobin protein that causes the red blood

cells to assume a sickle shape.

Sickle-cell anemia is caused by a genetic mutation in a single base of

the hemoglobin gene resulting in abnormal hemoglobin, called hemo-

globin S. Those afflicted by the disease are homozygous for the S al-

lele, and all their red blood cells “sickle.” Co-dominance is observable

with the sickle and normal alleles. Heterozygotes make 50 percent

normal hemoglobin and 50 percent sickle hemoglobin. Shown here is

a sickle hemoglobin red blood cell among normal red blood cells.

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