title: High polymorphism at the human melanocortin 1 receptor locus.
abstract: Variation in human skin/hair pigmentation is due to varied amounts of eumelanin (brown/black melanins) and phaeomelanin (red/yellow melanins) produced by the melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eu- and phaeomelanin production in the melanocytes, and MC1R mutations causing coat color changes are known in many mammals. We have sequenced the MC1R gene in 121 individuals sampled from world populations with an emphasis on Asian populations. We found variation at five nonsynonymous sites (resulting in the variants Arg67Gln, Asp84Glu, Val92Met, Arg151Cys, and Arg163Gln), but at only one synonymous site (A942G). Interestingly, the human consensus protein sequence is observed in all 25 African individuals studied, but at lower frequencies in the other populations examined, especially in East and Southeast Asians. The Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, and at a low frequency (7%) in Indians, but is at an exceptionally high frequency (70%) in East and Southeast Asians. The MC1R gene in common and pygmy chimpanzees, gorilla, orangutan, and baboon was sequenced to study the evolution of MC1R. The ancestral human MC1R sequence is identical to the human consensus protein sequence, while MC1R varies considerably among higher primates. A comparison of the rates of substitution in genes in the melanocortin receptor family indicates that MC1R has evolved the fastest. In addition, the nucleotide diversity at the MC1R locus is shown to be several times higher than the average nucleotide diversity in human populations, possibly due to diversifying selection.
authors: Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030, USA.
authors: B K
authors: BK
authors: Rana
authors: D
authors: D
authors: Hewett-Emmett
authors: L
authors: L
authors: Jin
authors: B H
authors: BH
authors: Chang
authors: N
authors: N
authors: Sambuughin
authors: M
authors: M
authors: Lin
authors: S
authors: S
authors: Watkins
authors: M
authors: M
authors: Bamshad
authors: L B
authors: LB
authors: Jorde
authors: M
authors: M
authors: Ramsay
authors: T
authors: T
authors: Jenkins
authors: W H
authors: WH
authors: Li
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D005787:Gene Frequency; D014644:Genetic Variation; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011323:Primates; D018043:Receptors, Corticotropin / Q000235:genetics*; D044101:Receptors, Melanocortin; D017386:Sequence Homology, Amino Acid; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D017931:DNA Primers; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D004247:DNA