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

We see evidence of regional genetic variation in response to local challenges, especially those posed by disease. Malaria, for example, is largely limited to warm climates because it is transmitted by a species of mosquito that can survive only in these regions. Historically, the disease has been devastating in Africa and the Mediterranean. As we saw in Chapter 21, the sickle allele of hemoglobin, S, has evolved to be present at high frequencies in these regions because in heterozygotes it confers some protection against the disease. But in homozygotes, the S allele is highly detrimental because it causes sickle-cell anemia. Homozygotes for the allele encoding normal hemoglobin are also at a disadvantage because they are entirely unprotected from the parasite.

The S allele is beneficial only in the presence of malaria. If there is no malaria in an area, the S allele is disadvantageous, so natural selection presumably acted rapidly to eliminate it in the ancestors of Europeans when they arrived in malaria-free regions. The continued high frequency of the S allele in Africans, some Mediterranean populations, and in populations descended recently from Africans (such as African-Americans) is, however, a reflection of the response of natural selection to a regional disease.

The hemoglobin genes are not the only genes that are under selection for resistance to malaria. Glucose-6-phosphate dehydrogenase (G6PD), a gene involved in glucose metabolism, is one of several other genes implicated. People who are heterozygotes for a mutation in the G6PD gene—and therefore have a G6PD enzyme deficiency—can develop severe anemia when they eat certain foods (most notably fava beans; hence, the condition is called favism). People who are heterozygotes for a mutation in the G6PD gene, however, also have increased resistance to malaria, apparently because they are better at clearing infected red blood cells from their bloodstream. In areas where malaria is common, the advantage of malaria resistance offsets the disadvantage of favism.

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Detailed evolutionary analysis of mutations in G6PD shows that favism has arisen multiple times, each time selectively favored because of its role in the body’s response to the malaria parasite. As expected, favism, like sickle-cell anemia, is mainly a feature of populations in malarial areas or of populations whose evolutionary roots lie in these areas.