title: Evidence for variable selective pressures at MC1R.
abstract: 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.
authors.affiliation: Institute of Molecular Medicine, Oxford, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Harding
authors.forename: E
authors.initials: E
authors.lastname: Healy
authors.forename: A J
authors.initials: AJ
authors.lastname: Ray
authors.forename: N S
authors.initials: NS
authors.lastname: Ellis
authors.forename: N
authors.initials: N
authors.lastname: Flanagan
authors.forename: C
authors.initials: C
authors.lastname: Todd
authors.forename: C
authors.initials: C
authors.lastname: Dixon
authors.forename: A
authors.initials: A
authors.lastname: Sajantila
authors.forename: I J
authors.initials: IJ
authors.lastname: Jackson
authors.forename: M A
authors.initials: MA
authors.lastname: Birch-Machin
authors.forename: J L
authors.initials: JL
authors.lastname: Rees
mesh_terms: D000349:Africa; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001208:Asia; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D005060:Europe; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016013:Likelihood Functions; D008543:Melanins / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D010858:Pigmentation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D044101:Receptors, Melanocortin; D012641:Selection, Genetic
chemical_list: D008543:Melanins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C041877:eumelanin