Human pigmentation variation: Evolution, genetic basis, and implications for public health

Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada L5L 1C6.
American Journal of Physical Anthropology (Impact Factor: 2.38). 01/2007; Suppl 45(S45):85-105. DOI: 10.1002/ajpa.20727
Source: PubMed


Pigmentation, which is primarily determined by the amount, the type, and the distribution of melanin, shows a remarkable diversity in human populations, and in this sense, it is an atypical trait. Numerous genetic studies have indicated that the average proportion of genetic variation due to differences among major continental groups is just 10-15% of the total genetic variation. In contrast, skin pigmentation shows large differences among continental populations. The reasons for this discrepancy can be traced back primarily to the strong influence of natural selection, which has shaped the distribution of pigmentation according to a latitudinal gradient. Research during the last 5 years has substantially increased our understanding of the genes involved in normal pigmentation variation in human populations. At least six genes have been identified using genotype/phenotype association studies and/or direct functional assays, and there is evidence indicating that several additional genes may be playing a role in skin, hair, and iris pigmentation. The information that is emerging from recent studies points to a complex picture where positive selection has been acting at different genomic locations, and for some genes only in certain population groups. There are several reasons why elucidating the genetics and evolutionary history of pigmentation is important. 1) Pigmentation is a trait that should be used as an example of how misleading simplistic interpretations of human variation can be. It is erroneous to extrapolate the patterns of variation observed in superficial traits such as pigmentation to the rest of the genome. It is similarly misleading to suggest, based on the "average" genomic picture, that variation among human populations is irrelevant. The study of the genes underlying human pigmentation diversity brings to the forefront the mosaic nature of human genetic variation: our genome is composed of a myriad of segments with different patterns of variation and evolutionary histories. 2) Pigmentation can be very useful to understand the genetic architecture of complex traits. The pigmentation of unexposed areas of the skin (constitutive pigmentation) is relatively unaffected by environmental influences during an individual's lifetime when compared with other complex traits such as diabetes or blood pressure, and this provides a unique opportunity to study gene-gene interactions without the effect of environmental confounders. 3) Pigmentation is of relevance from a public health perspective, because of its critical role in photoprotection and vitamin D synthesis. Fair-skinned individuals are at higher risk of several types of skin cancer, particularly in regions with high UVR incidence, and dark-skinned individuals living in high latitude regions are at higher risk for diseases caused by deficient or insufficient vitamin D levels.

Download full-text


Available from: Esteban Parra,
160 Reads
  • Source
    • "Hair color has also been described quantitatively using M index values in previous studies (Norton et al., 2006; Candille et al., 2012; Kenny et al., 2012; Beleza et al., 2013). Tristimulus colorimetry methods of measurement attempt to convey color in a way analogous to how it is perceived by the eye: reflectance is assessed at three broad wavelengths and a color is described in terms of its reflectance at these wavelengths as well as in the differences between them (Parra, 2007). These results may be conveyed in terms of the CIELab color system (developed by the Commission International d'Eclairage), which describes a particular color in terms of its position along three axes: light-dark (L*), red-green (a*), and yellow-blue (b*) (Weatherall and Coombs, 1992). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives The main goals of this study are to 1) quantitatively measure skin, hair, and iris pigmentation in a diverse sample of individuals, 2) describe variation within and between these samples, and 3) demonstrate how quantitative measures can facilitate genotype-phenotype association tests.Materials and Methods We quantitatively characterize skin, hair, and iris pigmentation using the Melanin (M) Index (skin) and CIELab values (hair) in 1,450 individuals who self-identify as African American, East Asian, European, Hispanic, or South Asian. We also quantify iris pigmentation in a subset of these individuals using CIELab values from high-resolution iris photographs. We compare mean skin M index and hair and iris CIELab values among populations using ANOVA and MANOVA respectively and test for genotype-phenotype associations in the European sample.ResultsAll five populations are significantly different for skin (P <2 × 10−16) and hair color (P <2 × 10−16). Our quantitative analysis of iris and hair pigmentation reinforces the continuous, rather than discrete, nature of these traits. We confirm the association of three loci (rs16891982, rs12203592, and rs12913832) with skin pigmentation and four loci (rs12913832, rs12203592, rs12896399, and rs16891982) with hair pigmentation. Interestingly, the derived rs12203592 T allele located within the IRF4 gene is associated with lighter skin but darker hair color.DiscussionThe quantitative methods used here provide a fine-scale assessment of pigmentation phenotype and facilitate genotype-phenotype associations, even with relatively small sample sizes. This represents an important expansion of current investigations into pigmentation phenotype and associated genetic variation by including non-European and admixed populations. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc.
    American Journal of Physical Anthropology 09/2015; DOI:10.1002/ajpa.22861 · 2.38 Impact Factor
  • Source
    • "). Subsequently, it has also been described in some animal groups, e.g., it was found in humans where it can influence skin coloration (Parra 2007). An accumulation of somatic mutations is expected to predominantly occur in large animals with a long life span (Otto and Hastings 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, the new phenomenon of intracolonial genetic variability within a single coral colony has been described. This connotes that coral colonies do not necessarily consist of only a single genotype, but may contain several distinct genotypes. Harboring more than one genotype could improve survival under stressful environmental conditions, e.g., climate change. However, so far it remained unclear whether the intracolonial genetic variability of the adult coral is also present in the gametes. We investigated the occurrence of intracolonial genetic variability in 14 mature colonies of the coral Acropora hyacinthus using eight microsatellite loci. A grid was placed over each colony before spawning, and the emerging egg/sperm bundles were collected separately in each grid. The underlying tissues as well as the egg/sperm bundles were genotyped to determine whether different genotypes were present. Within the 14 mature colonies, we detected 10 colonies with more than one genotype (intracolonial genetic variability). Four out of these 10 mature colonies showed a transfer of different genotypes via the eggs to the next generation. In two out of these four cases, we found additional alleles, and in the two other cases, we found only a subset of alleles in the unfertilized eggs. Our results suggest that during reproduction of A. hyacinthus, more than one genotype per colony is able to reproduce. We discuss the occurrence of different genotypes within a single coral colony and the ability for those to release eggs which are genetically distinct.
    Coral Reefs 03/2014; 33(1). DOI:10.1007/s00338-013-1102-5 · 3.32 Impact Factor
  • Source
    • "SLC24A5 and SLC45A2 in Europe, DCT in East Asia) or independent signals in European and East Asian groups (OCA2). These findings support an evolutionary model in which the most important changes in pigmentary traits occurred after the migration out-of-Africa and the separation of the lineages that gave rise to contemporary European and East Asian populations [5,12,22-25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1/ Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), 2/ Tests focused on the identification of high-frequency haplotypes with extended LD (iHS and Rsb) and 3/ Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation.
    BMC Evolutionary Biology 07/2013; 13(1):150. DOI:10.1186/1471-2148-13-150 · 3.37 Impact Factor
Show more