Abstract
Skin pigmentation is a complex, conspicuous, highly variable human trait that exhibits a remarkable correlation with latitude. The evolutionary history and genetic basis of skin color variation has been the subject of intense research in the last years. This article reviews the major hypotheses explaining skin color diversity and explores the implications of recent findings about the genes associated with skin pigmentation for understanding the evolutionary forces that have shaped the current patterns of skin color variation. A major aspect of these findings is that the genetic basis of skin color is less simple than previously thought and that geographic variation in skin pigmentation was influenced by the concerted action of different types of natural selection, rather than just by selective sweeps in a few key genes.
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References
Abe Y, Tamiya G, Nakamura T et al (2013) Association of melanogenesis genes with skin color variation among Japanese females. J Dermatol Sci 69:167–172. https://doi.org/10.1016/j.jdermsci.2012.10.016
Adhikari K, Mendoza-Revilla Sohail A et al (2019) A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigementation in Eurasia. Nat Commun 10:358. https://doi.org/10.1038/s414667-018-08147-0
Barsh GS (2003) What controls variation in human skin color? PLoS Biol 1:e27. https://doi.org/10.1371/journal.pbio.0000091
Basu Mallick C, Iliescu FM, Möls M et al (2013) The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent. PLoS Genet 9:e1003912. https://doi.org/10.1371/journal.pgen.1003912
Beleza S, Johnson NA, Candille SI et al (2013a) Genetic architecture of skin and eye color in an African-European admixed population. PLoS Genet 9:e1003372. https://doi.org/10.1371/journal.pgen.1003372
Beleza S, Santos AM, McEvoy B et al (2013b) The timing of pigmentation lightening in Europeans. Mol Biol Evol 30:24–35. https://doi.org/10.1093/molbev/mss207
Berg JJ, Coop G (2014) A population genetic signal of polygenic adaptation. PLoS Genet 10:e1004412. https://doi.org/10.1371/journal.pgen.1004412
Blum HF (1961) Does the melanin pigment of human skin have adaptive value? An essay in human ecology and the evolution of race. Q Rev Biol 36:50–63. https://doi.org/10.1086/403275
Bonilla C, Boxill LA, Mc Donald SA et al (2005) The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet. https://doi.org/10.1007/s00439-004-1251-2
Borradale DC, Kimlin MG (2012) Folate degradation due to ultraviolet radiation: possible implications for human health and nutrition. Nutr Rev. https://doi.org/10.1111/j.1753-4887.2012.00485.x
Brace S, Diekmann Y, Booth TJ et al (2019) Ancient genomes indicate population replacement in Early Neolithic Britain. Nat Ecol Evol 3:765–771. https://doi.org/10.1038/s41559-019-0871-9
Branda R, Eaton J (1978) Skin color and nutrient photolysis: an evolutionary hypothesis. Science 201:625–626. https://doi.org/10.1126/science.675247
Breton G, Schlebusch CM, Lombard M et al (2014) Lactase persistence alleles reveal partial east African ancestry of southern African Khoe pastoralists. Curr Biol 24:852–858. https://doi.org/10.1016/j.cub.2014.02.041
Byard PJ (1981) Quantitative genetics of human skin color. Am J Phys Anthropol 24:123–137. https://doi.org/10.1002/ajpa.1330240506
Chaplin G (2004) Geographic distribution of environmental factors influencing human skin coloration. Am J Phys Anthropol 125:292–302. https://doi.org/10.1002/ajpa.10263
Chaplin G, Jablonski NG (2009) Vitamin D and the evolution of human depigmentation. Am J Phys Anthropol 139:451–461. https://doi.org/10.1002/ajpa.21079
Chen H, Hey J, Slatkin M (2015) A hidden Markov model for investigating recent positive selection through haplotype structure. Theor Popul Biol 99:18–30. https://doi.org/10.1016/j.tpb.2014.11.001
Chevin LM, Hospital F (2008) Selective sweep at a quantitative trait locus in the presence of background genetic variation. Genetics 180:1645–1660. https://doi.org/10.1534/genetics.108.093351
Cook AL, Chen W, Thurber AE et al (2009) Analysis of cultured human melanocytes based on polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P loci. J Invest Dermatol 129:392–405. https://doi.org/10.1038/jid.2008.211
Coop G, Pickrell JK, Novembre J et al (2009) The role of geography in human adaptation. PLoS Genet 5:e1000500. https://doi.org/10.1371/journal.pgen.1000500
Crawford NG, Kelly DE, Hansen MEB et al (2017) Loci associated with skin pigmentation identified in African populations. Science 358:887. https://doi.org/10.1126/science.aan8433
Deng L, Xu S (2018) Adaptation of human skin color in various populations. Hereditas 155:1. https://doi.org/10.1186/s41065-017-0036-2
Edwards M, Bigham A, Tan J et al (2010) Association of the OCA2 polymorphism His615Arg with melanin content in East Asian populations: further evidence of convergent evolution of skin pigmentation. PLoS Genet 6:e1000867. https://doi.org/10.1371/journal.pgen.1000867
Eiberg H, Troelsen J, Nielsen M et al (2008) Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum Genet 123:177–187. https://doi.org/10.1007/s00439-007-0460-x
Elias PM, Williams ML (2016) Basis for the gain and subsequent dilution of epidermal pigmentation during human evolution: the barrier and metabolic conservation hypotheses revisited. Am J Phys Anthropol 161:189–207. https://doi.org/10.1002/ajpa.23030
Field Y, Boyle EA, Telis N et al (2016) Detection of human adaptation during the past 2000 years. Science 354:760–764
Graf J, Hodgson R, van Daal A (2005) Single nucleotide polymorphisms in theMATP gene are associated with normal human pigmentation variation. Hum Mutat 25:278–284. https://doi.org/10.1002/humu.20143
Greaves M (2014) Was skin cancer a selective force for black pigmentation in early hominin evolution? Proc R Soc B Biol Sci 281:20132955. https://doi.org/10.1098/rspb.2013.2955
Han J, Kraft P, Nan H et al (2008) A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet 4:e1000074. https://doi.org/10.1371/journal.pgen.1000074
Hancock AM, Witonsky DB, Ehler E et al (2010) Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proc Natl Acad Sci 107:8924–8930. https://doi.org/10.1073/pnas.0914625107
Harding RM, Healy E, Ray AJ et al (2000) Evidence for variable selective pressures at MC1R. Am J Hum Genet 66:1351–1361. https://doi.org/10.1086/302863
Hernandez-Pacheco N, Flores C, Alonso S et al (2017) Identification of a novel locus associated with skin colour in African-admixed populations. Sci Rep 7:44548. https://doi.org/10.1038/srep44548
Holick MF (1995) Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 61:638S–645S. https://doi.org/10.1093/ajcn/61.3.638S
Iliescu FM, Chaplin G, Rai N et al (2018) The influences of genes, the environment, and social factors on the evolution of skin color diversity in India. Am J Hum Biol 30:1–15. https://doi.org/10.1002/ajhb.23170
Jablonski NG (2004) The evolution of human skin and skin color. Annu Rev Anthropol 33:585–623. https://doi.org/10.1146/annurev.anthro.33.070203.143955
Jablonski NG (2006) Skin: a natural history. University of California Press, Berkeley
Jablonski NG, Chaplin G (2000) The evolution of human skin coloration. J Hum Evol 39:57–106. https://doi.org/10.1006/jhev.2000.0403
Jablonski NG, Chaplin G (2010) Human skin pigmentation as an adaptation to UV radiation. Proc Natl Acad Sci 107:8962–8968. https://doi.org/10.1073/pnas.0914628107
Jablonski NG, Chaplin G (2012) Human skin pigmentation, migration and disease susceptibility. Philos Trans R Soc B Biol Sci 367:785–792. https://doi.org/10.1098/rstb.2011.0308
Jablonski NG, Chaplin G (2017) The colours of humanity: the evolution of pigmentation in the human lineage. Philos Trans R Soc B Biol Sci 372:20160349. https://doi.org/10.1098/rstb.2016.0349
Jacobs LC, Wollstein A, Lao O et al (2013) Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans. Hum Genet 132:147–158. https://doi.org/10.1007/s00439-012-1232-9
Jeong C, Di Rienzo A (2014) Adaptations to local environments in modern human populations. Curr Opin Genet Dev 29:1–8. https://doi.org/10.1016/j.gde.2014.06.011
Klein RG (1999) The human career: human biological and cultural origins. University of Chicago Press, Chicago
Lalueza-Fox C, Rompler H, Caramelli D et al (2007) A melanocortin 1 receptor allele suggests varying pigmentation among neanderthals. Science 318:1453–1455. https://doi.org/10.1126/science.1147417
Lamason RL (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310:1782–1786. https://doi.org/10.1126/science.1116238
Lao O, de Gruijter JM, van Duijn K et al (2007) Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms. Ann Hum Genet 71:354–369. https://doi.org/10.1111/j.1469-1809.2006.00341.x
Lazaridis I, Patterson N, Mittnik A et al (2014) Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513:409–413. https://doi.org/10.1038/nature13673
Lin M, Siford RL, Martin AR et al (2018) Rapid evolution of a skin-lightening allele in southern African KhoeSan. Proc Natl Acad Sci 115:13324–13329. https://doi.org/10.1073/pnas.1801948115
Liu F, Wen B, Kayser M (2013) Colorful DNA polymorphisms in humans. Semin Cell Dev Biol 24:562–575. https://doi.org/10.1016/j.semcdb.2013.03.013
Liu F, Visser M, Duffy DL et al (2015) Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up. Hum Genet 134:823–835. https://doi.org/10.1007/s00439-015-1559-0
Lloyd-Jones LR, Robinson MR, Moser G et al (2017) Inference on the genetic basis of eye and skin color in an admixed population via bayesian linear mixed models. Genetics 206:1113–1126. https://doi.org/10.1534/genetics.116.193383/-/DC1.1
Loomis WF (1967) Skin-pigment regulation of Vitamin-D biosynthesis in man: variation in solar ultraviolet at different latitudes may have caused racial differentiation in man. Science 157:501–506. https://doi.org/10.1126/science.157.3788.501
Macholdt E, Lede V, Barbieri C et al (2014) Tracing pastoralist migrations to southern Africa with lactase persistence alleles. Curr Biol 24:875–879. https://doi.org/10.1016/j.cub.2014.03.027
Martin AR, Lin M, Granka JM et al (2017) An unexpectedly complex architecture for skin pigmentation in Africans. Cell 171:1340–1353. https://doi.org/10.1016/j.cell.2017.11.015
Mathieson I, Lazaridis I, Rohland N et al (2015) Genome-wide patterns of selection in 230 ancient Eurasians. Nature 528:499–503. https://doi.org/10.1038/nature16152
McEvoy B, Beleza S, Shriver MD (2006) The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model. Hum Mol Genet 15:R176–R181. https://doi.org/10.1093/hmg/ddl217
Miller CT, Beleza S, Pollen AA et al (2007) cis-Regulatory changes in kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. Cell 131:1179–1189. https://doi.org/10.1016/j.cell.2007.10.055
Myles S, Somel M, Tang K et al (2007) Identifying genes underlying skin pigmentation differences among human populations. Hum Genet 120:613–621. https://doi.org/10.1007/s00439-006-0256-4
Nielsen R, Akey JM, Jakobsson M et al (2017) Tracing the peopling of the world through genomics. Nature 541:302–310. https://doi.org/10.1038/nature21347
Norton HL, Kittles RA, Parra E et al (2007) Genetic evidence for the convergent evolution of light skin in Europeans and east Asians. Mol Biol Evol 24:710–722. https://doi.org/10.1093/molbev/msl203
Pagani L, Kivisild T, Tarekegn A et al (2012) Ethiopian genetic diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool. Am J Hum Genet 91:83–96. https://doi.org/10.1016/j.ajhg.2012.05.015
Parra EJ (2007) Human pigmentation variation: evolution, genetic basis, and implications for public health. Yearb Phys Anthropol 50:85–105. https://doi.org/10.1002/ajpa
Pickrell JK, Coop G, Novembre J et al (2009) Signals of recent positive selection in a worldwide sample of human populations. Genome Res 19:826–837. https://doi.org/10.1101/gr.087577.108
Pigafetta F, Lopes D (2002) Le Royaume de Congo & les contrées environnantes (1591); traduite & annotée par Willy Bal. Chandeigne/Unesco, Paris
Pinto JC, Oliveira S, Teixeira S et al (2016) Food and pathogen adaptations in the Angolan Namib desert: tracing the spread of lactase persistence and human African trypanosomiasis resistance into southwestern Africa. Am J Phys Anthropol 161:436–447. https://doi.org/10.1002/ajpa.23042
Praetorius C, Grill C, Stacey SN et al (2013) A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell 155:1022–1033. https://doi.org/10.1016/j.cell.2013.10.022
Pritchard JK, Di Rienzo A (2010) Adaptation—not by sweeps alone. Nat Rev Genet 11:665–667. https://doi.org/10.1038/nrg2880
Pritchard JK, Pickrell JK, Coop G (2010) The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr Biol 20:R208–R215. https://doi.org/10.1016/j.cub.2009.11.055
Quillen EE, Bauchet M, Bigham AW et al (2012) OPRM1 and EGFR contribute to skin pigmentation differences between Indigenous Americans and Europeans. Hum Genet 131:1073–1080. https://doi.org/10.1007/s00439-011-1135-1
Quillen EE, Norton HL, Parra EJ et al (2019) Shades of complexity: new perspectives on the evolution and genetic architecture of human skin. Am J Phys Anthropol 168:4–26. https://doi.org/10.1002/ajpa.23737
Reed DL, Light JE, Allen JM, Kirchman JJ (2007) Pair of lice lost or parasites regained: the evolutionary history of anthropoid primate lice. BMC Biol 5:1–11. https://doi.org/10.1186/1741-7007-5-7
Rees JL (2003) Genetics of hair and skin color. Annu Rev Genet. https://doi.org/10.1146/annurev.genet.37.110801.143233
Rees JL, Flanagan N (1999) Pigmentation, melanocortins and red hair. QJM 92:125–131. https://doi.org/10.1093/qjmed/92.3.125
Relethford JH (1997) Hemispheric difference in human skin color. Am J Phys Anthropol 104:449–457
Relethford JH (2002) Apportionment of global human genetic diversity based on craniometrics and skin color. Am J Phys Anthropol 118:393–398. https://doi.org/10.1002/ajpa.10079
Robins AH (2009) The evolution of light skin color: role of vitamin D disputed. Am J Phys Anthropol 139:447–450. https://doi.org/10.1002/ajpa.21077
Rogers AR, Iltis D, Wooding S (2004) Genetic variation at the MCIR locus and the time since loss of human body hair. Curr Anthropol 45:105–108
Shriver MD, Parra EJ (2000) Comparison of narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry. Am J Phys Anthropol 112:17–27
Shriver M, Parra E, Dios S et al (2003) Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet 112:387–399. https://doi.org/10.1007/s00439-002-0896-y
Smith J, Coop G, Stephens M, Novembre J (2018) Estimating time to the common ancestor for a beneficial allele. Mol Biol Evol 35:1003–1017. https://doi.org/10.1093/molbev/msy006
Stoneking M (2017) An introduction to molecular anthropology. Wiley, New York
Sturm RA (2009) Molecular genetics of human pigmentation diversity. Hum Mol, Genet
Sturm RA, Duffy DL (2012) Human pigmentation genes under environmental selection. Genome Biol 13:248. https://doi.org/10.1186/gb-2012-13-9-248
Sturm RA, Duffy DL, Zhao ZZ et al (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 82:424–431. https://doi.org/10.1016/j.ajhg.2007.11.005
Tsetskhladze ZR, Canfield VA, Ang KC et al (2012) Functional assessment of human coding mutations affecting skin pigmentation using zebrafish. PLoS ONE 7:e47398. https://doi.org/10.1371/journal.pone.0047398
Visser M, Kayser M, Palstra R-J (2012) HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res 22:446–455. https://doi.org/10.1101/gr.128652.111
Visser M, Palstra R-J, Kayser M (2014) Human skin color is influenced by an intergenic DNA polymorphism regulating transcription of the nearby BNC2 pigmentation gene. Hum Mol Genet 23:5750–5762. https://doi.org/10.1093/hmg/ddu289
Voight BF, Adams AM, Frisse LA et al (2005) Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.0507325102
Walsh S, Chaitanya L, Breslin K et al (2017) Global skin colour prediction from DNA. Hum Genet 136:847–863. https://doi.org/10.1007/s00439-017-1808-5
Wheeler PE (1985) The loss of functional body hair in man: the influence of thermal environment, body form and bipedality. J Hum Evol 14:23–28. https://doi.org/10.1016/S0047-2484(85)80091-9
Wilde S, Timpson A, Kirsanow K et al (2014) Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y. Proc Natl Acad Sci 111:4832–4837. https://doi.org/10.1073/pnas.1316513111
Wood AR, Esko T, Yang J et al (2014) Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 46:1173–1186
Yang Z, Zhong H, Chen J et al (2016) A genetic mechanism for convergent skin lightening during recent human evolution. Mol Biol Evol 33:1177–1187. https://doi.org/10.1093/molbev/msw003
Yang Z, Shi H, Ma P et al (2018) Darwinian positive selection on the pleiotropic effects of KITLG explain skin pigmentation and winter temperature adaptation in eurasians. Mol Biol Evol 35:2272–2283. https://doi.org/10.1093/molbev/msy136
Acknowledgements
I thank Anne-Maria Fehn for her comments and suggestions, and for her help in compiling the bibliography and preparing the figures. I would like also to thank two anonymous reviewers, whose comments helped to improve the initial version of this article. My own research in skin color was supported by the Portuguese Foundation for Science and Technology (FCT; PTDC/BIA-BDE/64044/2006).
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Rocha, J. The Evolutionary History of Human Skin Pigmentation. J Mol Evol 88, 77–87 (2020). https://doi.org/10.1007/s00239-019-09902-7
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DOI: https://doi.org/10.1007/s00239-019-09902-7