title: Global patterns of diversity and selection in human tyrosinase gene.
abstract: Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.
authors.affiliation: Evolutionary Biology Group, Estonian Biocentre, Tartu, Estonia ; Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Georgi
authors.initials: G
authors.lastname: Hudjashov
authors.forename: Richard
authors.initials: R
authors.lastname: Villems
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
mesh_terms: D024506:5' Flanking Region; D044466:Asian People; D005075:Biological Evolution; D044383:Black People; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000145:classification / Q000235:genetics*; D059645:Mutation Rate; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics* / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays; D044465:White People
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase
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