Genetics of skin pigmentation
The genetic basis of skin color across global populations is an age-old mystery. The dark skin of African populations, the ancestral state in humans, is protective in regions with high solar UV exposure. The dark skin, ancestral state of African populations protects them in regions with strong sun intensity. In contrast, the light skin of Europeans has a selective advantage in northerly latitudes due to higher sun-dependent generation of vitamin D. European skin is associated with a 10-20 fold increased risk of melanoma, (the deadliest form of skin cancer). Surprisingly, East Asians, although light-skinned, have very low risk of melanoma: their rates of disease are comparable to Africans. In addition, they do not carry the pervasive European light skin color genes (SLC24A5 & SLC45A2), which means that they must carry a genetic variation that functions similarly. We want to identify the East Asian light skin color gene through studying populations with a combination of the ancestral genes (African) and the primary East Asian light skin color genes, which would most likely be found in Indigenous populations originally from East Asia.
Skin color variation in Orang Asli tribes of Peninsular Malaysia
The aboriginal populations of Peninsular Malaysia, the Orang Asli (Malay for “original people”,are ideal for mapping the East Asian skin color genes. The Orang Asli represent 0.5% of the Malaysian population, and are comprised of three indigenous tribes: the Negrito, Senoi, and Proto-Malay, and encompass 18 ethnic subtribes. The Senoi are the largest in number among these tribes, followed by the Proto-Malay and the Negrito. The Negrito, who have dark-skin and curly hair, were the first occupants of South-East Asia and live as hunter-gatherers. The Proto-Malay, who have a lighter average skin color, straight hair, and epicanthal folds, work as farmer-traders. The Senoi have a wide range of skin color and wavy hair, living as both hunter-gatherers and traders, and are thought to descend from an admixture between the Negrito and an East Asian population. South Asians are lighter than West Africans but darker than Europeans, and have the commonly fixed SLC24A5A111T and infrequently the SLC45A2L374F. Similarly, we hypothesize that the Proto-Malay and the lighter Senoi, neither of whom are as light as Northeastern Asians, share a fixed derived skin color allele.
Native American genetic ancestry and pigmentation allele contributions to skin color in a Caribbean population
Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with genetically African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago Territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European genetic ancestry, the highest Native American genetic ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was –8 melanin units. Derived allele frequencies of SLC24A5A111T and SLC45A2L374F were 0.14 and 0.06, with single allele effect sizes of –6 and –4, respectively. Native American genetic ancestry by itself reduced pigmentation by more than 20 melanin units (range 24–29).