Identifying genes underlying skin pigmentation differences among human populations
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Skin pigmentation is a human phenotype that varies greatly among human populations and it has long been speculated that this variation is adaptive. We therefore expect the genes that contribute to these large differences in phenotype to show large allele frequency differences among populations and to possibly harbor signatures of positive selection. To identify the loci that likely contribute to among-population human skin pigmentation differences, we measured allele frequency differentiation among Europeans, Chinese and Africans for 24 human pigmentation genes from 2 publicly available, large scale SNP data sets. Several skin pigmentation genes show unusually large allele frequency differences among these populations. To determine whether these allele frequency differences might be due to selection, we employed a within-population test based on long-range haplotype structure and identified several outliers that have not been previously identified as putatively adaptive. Most notably, we identify the DCT gene as a candidate for recent positive selection in the Chinese. Moreover, our analyses suggest that it is likely that different genes are responsible for the lighter skin pigmentation found in different non-African populations.
KeywordsPositive selection Skin pigmentation Fst HapMap Perlegen SNP
We thank Ed Green for technical assistance; and David Hughes, Naim Matasci, Susan Ptak and Michael Lachmann for useful discussion. Supported by the Max Planck Society.
- Costin GE, Valencia JC, Wakamatsu K, Ito S, Solano F, Milac AL, Vieira WD, Yamaguchi Y, Rouzaud F, Petrescu AJ, Lamoreux ML, Hearing VJ (2005) Mutations in dopachrome tautomerase (Dct) affect eumelanin/pheomelanin synthesis, but do not affect intracellular trafficking of the mutant protein. Biochem J 391:249–259PubMedCrossRefGoogle Scholar
- Darwin C (1871) The descent of man. Princeton University Press, PrincetonGoogle Scholar
- Kong A, Gudbjartsson D, Sainz J, Jonsdottir G, Gudjonsson S, Richardsson B, Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson S, Frigge M, Thorgeirsson T, Gulcher J, Stefansson K (2002) A high-resolution recombination map of the human genome. Nat Genet 31:241–247PubMedGoogle Scholar
- Lamason RL, Mohideen M-APK, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O’Donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310:1782–1786PubMedCrossRefADSGoogle Scholar
- Lewontin RC (1972) The apportionment of human diversity. Evol Biol 6:391–398Google Scholar
- Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Bull WHO 77:694–703Google Scholar
- Sabeti PC, Reich DE, Higgins JM, Levine HZP, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D, Cooper R, Kwiatkowski D, Ward R, Lander ES (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419:832–837PubMedCrossRefADSGoogle Scholar
- Tishkoff SA, Varkonyi R, Cahinhinan N, Abbes S, Argyropoulos G, Destro-Bisol G, Drousiotou A, Dangerfield B, Lefranc G, Loiselet J, Piro A, Stoneking M, Tagarelli A, Tagarelli G, Touma EH, Williams SM, Clark AG (2001) Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293:455–462PubMedCrossRefGoogle Scholar