Red cell polymorphisms and malaria: an evolutionary approach

Abstract

Natural selection has made infectious agents a powerful driver of genome modification throughout human evolution. Malaria, a major killer in human societies, is one of the best examples to illustrate this phenomenon. The parasite (Plasmodium) is transmitted to humans through the bites of mosquitoes of the genus Anopheles and develops its deleterious effects by infecting red blood cells (erythrocytes). Plasmodium parasites date back to the dawn of mammalian evolution and P. falciparum, which causes the most severe form of malaria in humans, has a common evolutionary history with Homo sapiens. It has been suggested that malaria really became established with the change from hunter-gatherer to sedentary agricultural lifestyles about 10000 years ago. Micro- and macroepidemiological surveys have shown that the geographical distributions of falciparum malaria and of some genetic red cell disorders such as thalassemias, hemoglobinopathies (Hb S, Hb C and Hb E), metabolic disorders (especially G6PD deficiency) and some abnormalities in membrane proteins largely overlap. These erythrocyte-associated mutations have increased in frequency because of the protection they offer against death from malaria, as demonstrated by in vitro models and/or clinical studies. They seem to be regionally specific and of recent origin, and are useful tools for population genetics, particularly for reconstructing the history of migrations. Furthermore, exposure to malaria has produced remarkable genetic variation which is by no means restricted to these red cell polymorphisms.