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Identifying genes underlying skin pigmentation differences among human populations

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Abstract

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.

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References

  • Beaumont MA, Balding DJ (2004) Identifying adaptive genetic divergence among populations from genome scans. Mol Ecol 13:969–980

    Article  PubMed  CAS  Google Scholar 

  • Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN (2004) Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 74:1111–1120

    Article  PubMed  CAS  Google Scholar 

  • 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 391:249–259

    Article  PubMed  CAS  Google Scholar 

  • Darwin C (1871) The descent of man. Princeton University Press, Princeton

    Google Scholar 

  • del Marmol V, Beermann F (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381:165–168

    Article  PubMed  Google Scholar 

  • Guyonneau L, Murisier F, Rossier A, Moulin A, Beermann F (2004) Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice. Mol Cell Biol 24:3396–3403

    Article  PubMed  CAS  Google Scholar 

  • Harding RM, Healy E, Ray AJ, Ellis NS, Flanagan N, Todd C, Dixon C, Sajantila A, Jackson IJ, Birch-Machin MA, Rees JL (2000) Evidence for variable selective pressures at MC1R. Am J Hum Genet 66:1351–1361

    Article  PubMed  CAS  Google Scholar 

  • Hinds DA, Stuve LL, Nilsen GB, Halperin E, Eskin E, Ballinger DG, Frazer KA, Cox DR (2005) Whole-genome patterns of common DNA variation in three human populations. Science 307:1072–1079

    Article  PubMed  ADS  CAS  Google Scholar 

  • Izagirre N, Garcia I, Junquera C, de la Rua C, Alonso S (2006) A scan for signatures of positive selection in candidate loci for skin pigmentation in humans. Mol Biol Evol 23:1697–1706

    Article  PubMed  CAS  Google Scholar 

  • Jablonski NG (2004) The evolution of human skin and skin color. Ann Rev Anthro 33:585–623

    Article  Google 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 31:241–247

    PubMed  CAS  Google 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 310:1782–1786

    Article  PubMed  ADS  CAS  Google Scholar 

  • Lewontin RC (1972) The apportionment of human diversity. Evol Biol 6:391–398

    Google Scholar 

  • Makova K, Norton H (2005) Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans. Peptides 26:1901–1908

    Article  PubMed  CAS  Google Scholar 

  • Makova KD, Ramsay M, Jenkins T, Li W-H (2001) Human DNA sequence variation in a 6.6-kb region containing the melanocortin 1 receptor promoter. Genetics 158:1253–1268

    PubMed  CAS  Google Scholar 

  • Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Bull WHO 77:694–703

    Google Scholar 

  • Pollinger JP, Bustamante CD, Fledel-Alon A, Schmutz S, Gray MM, Wayne RK (2005) Selective sweep mapping of genes with large phenotypic effects. Genome Res 15:1809–1819

    Article  PubMed  CAS  Google Scholar 

  • Rana BK, Hewett-Emmett D, Jin L, Chang BHJ, Sambuughin N, Lin M, Watkins S, Bamshad M, Jorde LB, Ramsay M, Jenkins T, Li W-H (1999) High Polymorphism at the human melanocortin 1 receptor locus. Genetics 151:1547–1557

    PubMed  CAS  Google Scholar 

  • Rees JL (2003) Genetics of hair and skin color. Annu Rev Genet 37:67–90

    Article  PubMed  CAS  Google Scholar 

  • Relethford JH (2002) Apportionment of global human genetic diversity based on craniometrics and skin color. Am J Phys Anthropol 118:393–398

    Article  PubMed  Google 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 419:832–837

    Article  PubMed  ADS  CAS  Google Scholar 

  • Sabeti PC, Schaffner SF, Fry B, Lohmueller J, Varilly P, Shamovsky O, Palma A, Mikkelsen TS, Altshuler D, Lander ES (2006) Positive natural selection in the human lineage. Science 312:1614–1620

    Article  PubMed  ADS  CAS  Google Scholar 

  • Soejima M, Tachida H, Ishida T, Sano A, Koda Y (2006) Evidence for recent positive selection at the human AIM1 locus in a European population. Mol Biol Evol 23:179–188

    Article  PubMed  CAS  Google Scholar 

  • Sturm RA, Teasdale RD, Box NF (2001) Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 277:49–62

    Article  PubMed  CAS  Google Scholar 

  • Tang K, Wong LP, Lee EJD, Chong SS, Lee CGL (2004) Genomic evidence for recent positive selection at the human MDR1 gene locus. Hum Mol Genet 13:783–797

    Article  PubMed  CAS  Google Scholar 

  • The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299

    Article  ADS  Google 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 293:455–462

    Article  PubMed  CAS  Google Scholar 

  • Tomita Y, Suzuki T (2004) Genetics of pigmentary disorders. Am J Med Genet 131C:75–81

    Article  Google Scholar 

  • Toyofuku K, Wada I, Spritz RA, Hearing VJ (2001a) The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochem J 355:259–269

    Article  PubMed  CAS  Google Scholar 

  • Toyofuku K, Wada I, Valencia JC, Kushimoto T, Ferrans VJ, Hearing VJ (2001b) Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. FASEB J 15:2149–2161

    Article  PubMed  CAS  Google Scholar 

  • Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of recent positive selection in the human genome. PLoS Biol 4:e72

    Article  PubMed  Google Scholar 

  • Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370

    Article  Google Scholar 

Download references

Acknowledgments

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.

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Correspondence to Sean Myles.

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Myles, S., Somel, M., Tang, K. et al. Identifying genes underlying skin pigmentation differences among human populations. Hum Genet 120, 613–621 (2007). https://doi.org/10.1007/s00439-006-0256-4

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  • DOI: https://doi.org/10.1007/s00439-006-0256-4

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