{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:16:13Z","timestamp":1791216973884,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1999,4,1]],"date-time":"1999-04-01T00:00:00Z","timestamp":922924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/genetics\/151.4.1547","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T03:04:20Z","timestamp":1619579060000},"page":"1547-1557","source":"Crossref","is-referenced-by-count":240,"title":["High Polymorphism at the Human Melanocortin 1 Receptor Locus"],"prefix":"10.1093","volume":"151","author":[{"given":"Brinda K","family":"Rana","sequence":"first","affiliation":[{"name":"Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hewett-Emmett","sequence":"additional","affiliation":[{"name":"Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny H-J","family":"Chang","sequence":"additional","affiliation":[{"name":"Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naymkhishing","family":"Sambuughin","sequence":"additional","affiliation":[{"name":"Neurology Research, Phoenix, Arizona 85013"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lin","sequence":"additional","affiliation":[{"name":"Mackay Memorial Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn B","family":"Jorde","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ramsay","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, South African Institute for Medical Research, Johannesburg, South Africa 2050"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trefor","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, South African Institute for Medical Research, Johannesburg, South Africa 2050"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hsiung","family":"Li","sequence":"additional","affiliation":[{"name":"Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,4,1]]},"reference":[{"key":"2022010314432139000_R1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1073\/pnas.92.5.1789","article-title":"Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides","volume":"92","author":"Abdel-Malek","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022010314432139000_R2","first-page":"207","article-title":"Pigmentation and some other morphological characters","volume-title":"Human Biology: An Introduction to Human Evolution, Variation, Growth, and Ecology","author":"Barnicot","year":"1977","edition":"Ed. 2"},{"key":"2022010314432139000_R3","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/hmg\/6.11.1891","article-title":"Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair","volume":"11","author":"Box","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"2022010314432139000_R4","first-page":"304","volume-title":"The History and Geography of Human Genes","author":"Cavalli-Sforza","year":"1994"},{"key":"2022010314432139000_R5","first-page":"266","volume-title":"The History and Geography of Human Genes","author":"Cavalli-Sforza","year":"1994"},{"key":"2022010314432139000_R6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0014-5793(92)80820-7","article-title":"Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA","volume":"309","author":"Chhajlani","year":"1992","journal-title":"FEBS Lett."},{"key":"2022010314432139000_R7","first-page":"287","article-title":"The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation","volume":"51","author":"Cone","year":"1996","journal-title":"Recent Prog. Horm. Res."},{"key":"2022010314432139000_R8","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1006\/bbrc.1994.2067","article-title":"Evidence for alternate points of attachment for \u03b1-MSH and its stereoisomer [Nle4, D-Phe7]-\u03b1-MSH at the melanocortin-1 receptor","volume":"202","author":"Frandberg","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2022010314432139000_R9","doi-asserted-by":"crossref","first-page":"8246","DOI":"10.1016\/S0021-9258(18)53088-X","article-title":"Molecular cloning of a novel melanocortin receptor","volume":"268","author":"Gantz","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2022010314432139000_R10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1469-1809.1964.tb00457.x","article-title":"Studies on the inheritance of human skin colour","volume":"28","author":"Harrison","year":"1964","journal-title":"Ann. Hum. Genet."},{"key":"2022010314432139000_R11","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/0020-711X(87)90095-4","article-title":"Mammalian tyrosinase: the critical regulatory control point in melanocyte pigmentation","volume":"19","author":"Hearing","year":"1987","journal-title":"Int. J. Biochem."},{"key":"2022010314432139000_R12","first-page":"3","volume-title":"Determination of skin color: melanocytes and melanization","author":"Hearing","year":"1993"},{"key":"2022010314432139000_R13","first-page":"261","article-title":"Biology of Melanocytes","volume-title":"Dermatology In General Medicine","author":"Jimbow","year":"1993","edition":"Ed. 4"},{"key":"2022010314432139000_R14","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s003359900090","article-title":"Red coat color in holstein cattle is associated with a deletion in the MSHR gene","volume":"7","author":"Joerg","year":"1996","journal-title":"Mamm. 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