Simulating hemoglobin history.

Abstract

In one of the truly classic works in anthropological genetics, Frank Livingstone established the interrelationships between agriculture, mosquito ecology, malaria, and, consequently, the frequencies of sickle cell hemoglobin in West Africa. A major inference from Livingstone's study was the recency of malaria as a selective agent in human populations, only becoming significant after the adoption of agriculture in the last few thousand years. Clines of the abnormal hemoglobin alleles might therefore represent continuing waves of advance of adaptive alleles. In order to model the complex interaction of several hemoglobin alleles, selection, and gene flow spreading adaptive mutants, Livingstone turned to computer simulation. Numerous insights concerning the competitive increase of different alleles (hemoglobins S, C, and E and thalassemia), the rate of allele spread under different migration scenarios, including the potential importance of long-range migration, came out of these studies. These experiments also stimulated others to search for mechanisms that might increase the diffusion rate of hemoglobin variants, including kin-structured migration and epidemic disease selection. Recent molecular studies have substantiated major aspects of Livingstone's work (including the recent origin of falciparum malaria) and posed challenges to some of his assumptions (such as the number of mutations to hemoglobins S and E). But whatever the fate of his specific hypotheses, his emphasis on the interaction of genetics, ecology, and culture stands as a model for the anthropological approach to the understanding of human variation and evolution.