Evidence for variable selective pressures at MC1R.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Harding, R M; Healy, E; Ray, A J; Ellis, N S; Flanagan, N; Todd, C; Dixon, C; Sajantila, A; Jackson, I J; Birch-Machin, M A; Rees, J L
Year of Publication: 2000
Journal: Am J Hum Genet
Volume: 66
Issue: 4
Pagination: 1351-61
Date Published: 2000 Apr
Publication Language: eng
ISSN: 0002-9297
Keywords: Africa, African Continental Ancestry Group, Amino Acid Sequence, Amino Acid Substitution, Asia, Base Sequence, Europe, Genetic Variation, Haplotypes, Humans, Likelihood Functions, Melanins, Models, Genetic, Molecular Sequence Data, Mutation, Phylogeny, pigmentation, Polymorphism, Genetic, Receptors, Corticotropin, Receptors, Melanocortin, Selection, Genetic

It is widely assumed that genes that influence variation in skin and hair pigmentation 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 populations, for evidence of selection. We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although 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 that levels of MC1R polymorphism simply reflect neutral expectations under relaxation of strong functional constraint outside Africa.

DOI: 10.1086/302863
Alternate Journal: Am. J. Hum. Genet.