Evidence for variable selective pressures at MC1R

It is widely assumed that genes that influence variation in skin and hair p igmentation are under selection. To date, the melanocortin 1 receptor (MC1R ) is the only gene identified that explains substantial phenotypic variance in human pigmentation. Here we investigate MC1R polymorphism in several po pulations, for evidence of selection. We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin produc tion (black pigmentation) appears to be evolutionarily deleterious. Althoug h many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show tha t levels of MC1R polymorphism simply reflect neutral expectations under rel axation of strong functional constraint outside Africa.