With such obviously harmful effects, it is surprising to find the sickle-cell allele so frequent in some populations. The highest allele frequencies are found in western and central African populations, reaching levels close to 20 percent; values are also moderately high in some Greek and Asiatic Indian populations. How do we explain such a phenomenon? Obviously, the allele originated from a simple mutation, but why did it increase in frequency?
The answer lies in yet another kind of disease, one that exerts enormous selective pressure. In those areas of the world where the sickle-cell allele is found in highest frequency, malaria is also found. Caused by a single-celled parasite, this debilitating infectious disease is transmitted to humans by mosquitoes. In areas that are endemically infected, many individuals suffer sharply lower reproductive success, owing to high infant mortality rates or to lowered vitality as adults.
Such a geographical correlation between malarial incidence and distribution of the sickle-cell allele is indirect evidence of a biological correlation. Further confirmation was provided by British biologist A.C. Allison in the 1950s. Volunteers from the Luo tribe of eastern Africa with known genotypes were injected with the malarial parasite. The ethics concerning human subjects would preclude such experimentation today; even when the original study was conducted, its justification was questionable. A short time following infection, results showed that heterozygous carriers of the sickle-cell allele were much more resistant to malarial infection than the homozygous "normals." Apparently, carriers resist infection because their red blood cells provide a less conducive environment for the malarial parasite to reproduce itself. As a result, the parasite often dies before widely infecting the body of a carrier. But for the homozygous "normals," the infection usually persists.
A genetic trait (such as sickle-cell trait) that provides a reproductive advantage in certain environments is a clear example of natural selection in action among human populations. The precise evolutionary mechanism in the sickle-cell example is termed a balanced polymorphism.