CASE 4 MALARIA: CO-EVOLUTION OF HUMANS AND A PARASITE

In addition to allowing alleles to be either eliminated or fixed, natural selection can also maintain an allele at some intermediate frequency between 0% and 100%. This form of natural selection is called balancing selection, and it acts to maintain two or more alleles in a population. A simple case is members of a species that face different conditions depending upon where they live. One allele might be favored by natural selection in a dry area, but a different one favored in a wet area. Taking the species as a whole, these alleles are maintained by natural selection at intermediate frequencies.

Another example of balancing selection occurs when the heterozygote’s fitness is higher than that of either of the homozygotes, resulting in selection that ensures that both alleles remain in the population at intermediate frequencies. This form of balancing selection is called heterozygote advantage, and it is exemplified by human populations in Africa, where malaria has been a long-standing disease. Because the malaria parasite spends part of its life cycle in human red blood cells, mutations in the hemoglobin molecule that affect the structure of the red blood cells have a negative impact on the parasite and can reduce the severity of malarial attacks.

Two alleles of the gene for one of the subunits of hemoglobin are A and S (Chapter 15). The A allele codes for normal hemoglobin, resulting in fully functional, round red blood cells. The S allele encodes a polypeptide that differs from the A allele’s product in just a single amino acid, which is enough to cause the molecules to aggregate end to end, so the red blood cell is distorted into a sickle.

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In regions of the world with malaria, heterozygous individuals (SA) have an advantage over homozygous individuals (SS and AA). SS homozygotes are protected against malaria, but they are burdened with severe sickling disease. Sickle-shaped red blood cells can block capillaries, and therefore people with the SS genotype are prone to debilitating, painful, and sometimes fatal episodes resulting from capillary blockage. AA homozygotes lack sickling disease but are vulnerable to malaria. SA heterozygotes, however, do not have severe sickling disease and have some protection from malaria. As a result, natural selection maintains both the S and A alleles in the population at intermediate frequencies.

In areas where there is no malaria, this balance is shifted. Many African-Americans, descended from Africans upon whom natural selection operated in favor of the heterozygote, still carry the S allele, even though the allele is no longer useful to them in their malaria-free environment. If natural selection were to run its course among African-Americans, the S allele would gradually be eliminated. However, this is a slow process, and many more people will continue to suffer from sickle-cell anemia before it is complete.