Human Genetics

, Volume 120, Issue 5, pp 613–621 | Cite as

Identifying genes underlying skin pigmentation differences among human populations

  • Sean Myles
  • Mehmet Somel
  • Kun Tang
  • Janet Kelso
  • Mark Stoneking
Original Investigation

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.

Keywords

Positive selection Skin pigmentation Fst HapMap Perlegen SNP 

Supplementary material

439_2006_256_MOESM1_ESM.xls (33 kb)
Supplementary material

References

  1. Beaumont MA, Balding DJ (2004) Identifying adaptive genetic divergence among populations from genome scans. Mol Ecol 13:969–980PubMedCrossRefGoogle Scholar
  2. 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 74:1111–1120PubMedCrossRefGoogle Scholar
  3. 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
  4. Darwin C (1871) The descent of man. Princeton University Press, PrincetonGoogle Scholar
  5. del Marmol V, Beermann F (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381:165–168PubMedCrossRefGoogle Scholar
  6. Guyonneau L, Murisier F, Rossier A, Moulin A, Beermann F (2004) Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice. Mol Cell Biol 24:3396–3403PubMedCrossRefGoogle Scholar
  7. 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 66:1351–1361PubMedCrossRefGoogle Scholar
  8. 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 307:1072–1079PubMedCrossRefADSGoogle Scholar
  9. 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 23:1697–1706PubMedCrossRefGoogle Scholar
  10. Jablonski NG (2004) The evolution of human skin and skin color. Ann Rev Anthro 33:585–623CrossRefGoogle Scholar
  11. 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
  12. 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
  13. Lewontin RC (1972) The apportionment of human diversity. Evol Biol 6:391–398Google Scholar
  14. Makova K, Norton H (2005) Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans. Peptides 26:1901–1908PubMedCrossRefGoogle Scholar
  15. 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 158:1253–1268PubMedGoogle Scholar
  16. Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Bull WHO 77:694–703Google Scholar
  17. 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 15:1809–1819PubMedCrossRefGoogle Scholar
  18. 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 151:1547–1557PubMedGoogle Scholar
  19. Rees JL (2003) Genetics of hair and skin color. Annu Rev Genet 37:67–90PubMedCrossRefGoogle Scholar
  20. Relethford JH (2002) Apportionment of global human genetic diversity based on craniometrics and skin color. Am J Phys Anthropol 118:393–398PubMedCrossRefGoogle Scholar
  21. 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
  22. 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 312:1614–1620PubMedCrossRefADSGoogle Scholar
  23. 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 23:179–188PubMedCrossRefGoogle Scholar
  24. Sturm RA, Teasdale RD, Box NF (2001) Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 277:49–62PubMedCrossRefGoogle Scholar
  25. 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 13:783–797PubMedCrossRefGoogle Scholar
  26. The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299CrossRefADSGoogle Scholar
  27. 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
  28. Tomita Y, Suzuki T (2004) Genetics of pigmentary disorders. Am J Med Genet 131C:75–81CrossRefGoogle Scholar
  29. 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 355:259–269PubMedCrossRefGoogle Scholar
  30. 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 15:2149–2161PubMedCrossRefGoogle Scholar
  31. Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of recent positive selection in the human genome. PLoS Biol 4:e72PubMedCrossRefGoogle Scholar
  32. Weir BS, Cockerham CC (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Sean Myles
    • 1
  • Mehmet Somel
    • 1
  • Kun Tang
    • 1
  • Janet Kelso
    • 1
  • Mark Stoneking
    • 1
  1. 1.Department of Evolutionary GeneticsMax Planck Institute for Evolutionary AnthropologyLeipzigGermany

Personalised recommendations