Signatures of Positive Selection in Genes Associated with Human Skin Pigmentation as Revealed from Analyses of Single Nucleotide Polymorphisms
2007/01/18 by O. Lao, Óscar Lao, J. M. de Gruijter +7 · 241 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Nursing · #Adaptation (eye) #Biochemical Analysis and Sensing Techniques #Biology #Candidate gene #Evolutionary biology #Gene #Genetic variation #Genetics #Genome #Genotype #Human genetic variation #Human genome #Phenotype #Selection (genetic algorithm) #Single-nucleotide polymorphism #Skin Protection and Aging #melanin and skin pigmentation
paper · doi:10.1111/j.1469-1809.2006.00341.x
published in Annals of Human Genetics 71(3), 354-369 (Wiley)
openalex publication_date 2007/01/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract
Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.
Citations
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- Global skin colour prediction from DNA
- Potential etiologic and functional implications of genome-wide association loci for human diseases and traits
- Which evolutionary processes influence natural genetic variation for phenotypic traits?
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- Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y
- DNA-based prediction of human externally visible characteristics in forensics: Motivations, scientific challenges, and ethical considerations
- Parallel Adaptation: One or Many Waves of Advance of an Advantageous Allele?
- A genomewide association study of skin pigmentation in a South Asian population. [europepmc]
- cis-Regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. [europepmc]
- Evidence that stress to the epidermal barrier influenced the development of pigmentation in humans. [europepmc]
- Predicting phenotype from genotype: normal pigmentation. [europepmc]
- Barrier requirements as the evolutionary "driver" of epidermal pigmentation in humans. [europepmc]
- Detecting the Genetic Signature of Natural Selection in Human Populations: Models, Methods, and Data. [europepmc]
- A global view of the OCA2-HERC2 region and pigmentation. [europepmc]
- Evolutionary forces shaping genomic islands of population differentiation in humans. [europepmc]
- Human pigmentation genes under environmental selection. [europepmc]
- Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry. [europepmc]
- Recent human adaptation: genomic approaches, interpretation and insights. [europepmc]
- A polymorphic p53 response element in KIT ligand influences cancer risk and has undergone natural selection. [europepmc]
- A hidden Markov model for investigating recent positive selection through haplotype structure. [europepmc]
- Revisiting classic clines in Drosophila melanogaster in the age of genomics. [europepmc]
- Ancestry, admixture and fitness in Colombian genomes. [europepmc]
- Pigeonetics takes flight: Evolution, development, and genetics of intraspecific variation. [europepmc]
- Global skin colour prediction from DNA. [europepmc]
- Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy. [europepmc]
- Adaptation of human skin color in various populations. [europepmc]
- Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations. [europepmc]
- SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation. [europepmc]
- The evolution of skin pigmentation-associated variation in West Eurasia. [europepmc]
- Chemical and biochemical control of skin pigmentation with special emphasis on mixed melanogenesis. [europepmc]
- The evolution of human skin pigmentation involved the interactions of genetic, environmental, and cultural variables. [europepmc]
- Direct detection of natural selection in Bronze Age Britain. [europepmc]
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