Notes on Sickle‐cell Polymokphism

Abstract

Summary 1. In Africa, as in the United States, the great majority of cases of sickle‐cell anaemia are homozygous for the sickle‐cell gene. 2. Carriers of the sickle‐cell trait, i.e. individuals heterozygous for the sickle‐cell gene, occur in frequencies up to 40 % in Africa, 30 % in India and 17 % in Greece. It is difficult to explain the distribution of the sickle‐cell trait in terms of ancestral origins alone. 3. The incidence of sickle‐cell anaemia is not accurately known, but there is indirect evidence that in Africa, as in the United States, the majority of homozygotes for the sickle‐cell gene are affected. A minority of these homozygotes reaches adult life and reproduces. It is estimated that the fitness of the sickle‐cell homozygote is not more than a quarter that of the heterozygote. 4. The elimination of sickle‐cell genes in cases dying of sickle‐cell anaemia is so rapid that it is very unlikely + hat these genes could be replaced by reourrent mutation. It appears that those who are heterozygous for the sickle‐cell gene are naturally resistant to subtertian malaria, so that they have a selective advantage over the normal homozygotes in regions where malaria is hyperendemic. The sickle‐cell polymorphism would then be the result of a balance determined mainly by the severity of subtertian malaria, which would tend to increase the frequency of the gene, and the elimination of genes in cases of sickle‐cell anaemia. The sickle‐cell trait attains high frequencies, in fact, only in regions where malaria is severe. 5. It is estimated that the fitness of the sickle‐cell heterozygote in malarious environments is 1–26 X the fitness of the normal homozygote. 6. The expected rate of change of the sickle‐cell carrier frequency in populations under different conditions has been calculated. In two instances such an estimate corresponds approximately with the observed data. It seems that the incidence of the sickle‐cell trait may be greater in adults than in young children in populations exposed to malaria, as expected. And the United States Negroes have a lower frequency of the sickle‐cell trait than would be expected on the basis of a one‐third admixture with Caucasian and Indian blood. The fall in frequency would correspond to an elimination of three‐quarters of the homozygotes without heterosis for about 12 generations, i.e. some 300 years.

A First Formal Link between the Price Equation and an Optimization Program

“…It is interesting to consider another contrary case, that of sickle-cell anaemia (Allison, 1954). At the equilibrium with over-dominance, the hypotheses of the first two results do not hold.…”

Environmental correlates of inversion frequencies in natural populations of seaweed flies (Coelopa frigida)

“…Despite many years of endeavour there are still rather few examples for which a clear link has been established between specific environmental variables and allele frequencies. Among the best known cases are the visible polymorphisms in Biston betularia (Brakefield, 1987) and Cepaea nemoralis (Cain and Shepphard, 1954), allozyme polymorphisms in Mytilus edulis (Koehn, 1978) and Drosophila melanogaster (van Delden, 1982), and of course, sickle cell disease in man (Allison, 1954). Even in these species a complete description of the selection pressures involved is not yet available.…”

Changes of gene-frequency in Cepaea nemoraus (L.)

“…In most of these cases the action of natural selection has been inferred, but only in the studies on Panaxia has it been possible to obtain a precise estimate of the magnitude of the selective forces acting upon an individual Mendelian population. Allison (1954) has also made such an estimate in his studies of human sickle-cell polymorphism, but it was calculated for a static population.…”