Genetics

The understanding of the genetic mechanisms underlying human skin color variation is still incomplete, however genetic studies have discovered a number of genes that affect human skin color in specific populations, and have shown that this happens independently of other physical features such as eye and hair color. Different populations have different allele frequencies of these genes, and it is the combination of these allele variations that bring about the complex, continuous variation in skin coloration we can observe today in modern humans. Population and admixture studies suggest a 3-way model for the evolution of human skin color, with dark skin evolving in early hominids in sub-Saharan Africa and light skin evolving independently in Europe and East Asia after modern humans had expanded out of Africa.

Dark skinedit

All modern humans share a common ancestor who lived around 200,000 years ago in Africa. Comparisons between known skin pigmentation genes in chimpanzees and modern Africans show that dark skin evolved along with the loss of body hair about 1.2 million years ago and that this common ancestor had dark skin. Investigations into dark skinned populations in South Asia and Melanesia indicate that skin pigmentation in these populations is due to the preservation of this ancestral state and not due to new variations on a previously lightened population.

• MC1R

The melanocortin 1 receptor (MC1R) gene is primarily responsible for determining whether pheomelanin and eumelanin is produced in the human body. Research shows at least 10 differences in MC1R between African and chimpanzee samples and that the gene has probably undergone a strong positive selection (a selective sweep) in early Hominins around 1.2 million years ago. This is consistent with positive selection for the high-eumelanin phenotype seen in Africa and other environments with high UV exposure.

Light skinedit

For the most part, the evolution of light skin has followed different genetic paths in European and East Asian populations. Two genes however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in both European and East Asian populations. They are thought to have originated after humans spread out of Africa but before the divergence of the European and Asian lineages around 30,000 years ago. Two subsequent genome-wide association studies found no significant correlation between these genes and skin color, and suggest that the earlier findings may have been the result of incorrect correction methods and small panel sizes, or that the genes have an effect too small to be detected by the larger studies.

• KITLG

The KIT ligand (KITLG) gene is involved in the permanent survival, proliferation and migration of melanocytes. A mutation in this gene, A326G (rs642742), has been positively associated with variations of skin color in African-Americans of mixed West African and European descent and is estimated to account for 15–20% of the melanin difference between African and European populations. This allele shows signs of strong positive selection outside Africa and occurs in over 80% of European and Asian samples, compared with less than 10% in African samples.

• ASIP

Agouti signalling peptide (ASIP) acts as an inverse agonist, binding in place of alpha-MSH and thus inhibiting eumelanin production. Studies have found two alleles in the vicinity of ASIP are associated with skin color variation in humans. One, rs2424984 has been identified as an indicator of skin reflectance in a forensics analysis of human phenotypes across Caucasian, African-American, South Asian, East Asian, Hispanic and Native American populations and is about three times more common in non-African populations than in Africa. The other allele, 8188G (rs6058017) is significantly associated with skin color variation in African-Americans and the ancestral version occurs in only 12% of European and 28% of East Asian samples compared with 80% of West African samples.

Europeedit

A number of genes have been positively associated with the skin pigmentation difference between European and non-European populations. Mutations in SLC24A5 and SLC45A2 are believed to account for the bulk of this variation and show very strong signs of selection. A variation in TYR has also been identified as a contributor.

Research indicates the selection for the light-skin alleles of these genes in Europeans is comparatively recent, having occurred later than 20,000 years ago and perhaps as recently as 12,000 to 6,000 years ago. In the 1970s, Luca Cavalli-Sforza suggested that the selective sweep that rendered light skin ubiquitous in Europe might be correlated with the advent of farming and thus have taken place only around 6,000 years ago; This scenario found support in a 2014 analysis of mesolithic (7,000 years old) hunter-gatherer DNA from La Braña, Spain, which showed a version of these genes not corresponding with light skin color. In 2015 researchers analysed for light skin genes in the DNA of 94 ancient skeletons ranging from 8,000 to 3,000 years old from Europe and Russia. They found c. 8,000-year-old hunter-gatherers in Spain, Luxembourg, and Hungary were dark skinned while similarly aged hunter gatherers in Sweden were light skinned (having predominately derived alleles of SLC24A5, SLC45A2 and also HERC2/OCA2). Neolithic farmers entering Europe at around the same time were intermediate, being nearly fixed for the derived SLC24A5 variant but only having the derived SLC45A2 allele in low frequencies. The SLC24A5 variant spread very rapidly throughout central and southern Europe from about 8,000 years ago, whereas the light skin variant of SLC45A2 spread throughout Europe after 5,800 years ago.

• SLC24A5

Solute carrier family 24 member 5 (SLC24A5) regulates calcium in melanocytes and is important in the process of melanogenesis. The SLC24A5 gene's derived Ala111Thr allele (rs1426654) has been shown to be a major factor in light skin pigmentation and is common in Western Eurasia. Recent studies have found that the variant represents as much as 25–40% of the average skin tone difference between Europeans and West Africans. This derived allele is a reliable predictor of phenotype across a range of populations. It has been the subject of recent selection in Western Eurasia, and is fixed in European populations.

• SLC45A2

Solute carrier family 45 member 2 (SLC45A2 or MATP) aids in the transport and processing of tyrosine, a precursor to melanin. It has also been shown to be one of the significant components of the skin color of modern Europeans through its Phe374Leu (rs16891982) allele that has been directly correlated with skin color variation across a range of populations. This variation is ubiquitous in European populations but extremely rare elsewhere and shows strong signs of selection.

• TYR

The TYR gene encodes the enzyme tyrosinase, which is involved in the production of melanin from tyrosine. It has an allele, Ser192Tyr (rs1042602), found solely in 40–50% of Europeans and linked to light-colored skin in studies of South Asian and African-American populations.

East Asiaedit

A number of genes known to affect skin color have alleles that show signs of positive selection in East Asian populations. Of these only OCA2 has been directly related to skin color measurements, while DCT, MC1R and ATTRN are marked as candidate genes for future study.

• OCA2

Oculocutaneous albinism II (OCA2) assists in the regulation of pH in melanocytes. The OCA2 gene's derived His615Arg (rs1800414) allele has been shown to account for about 8% of the skin tone difference between African and East Asian populations in studies of an East Asian population living in Toronto and a Chinese Han population. This variant is essentially restricted to East Asia, with highest frequencies in Eastern East Asia (49–63%), midrange frequencies in Southeast Asia, and the lowest frequencies in Western China and some Eastern European populations.

• Candidate Genes

A number of studies have found genes linked to human skin pigmentation that have alleles with statistically significant frequencies in Chinese and East Asian populations. While not linked to measurements of skin tone variation directly, dopachrome tautomerase (DCT or TYRP2 rs2031526), melanocortin 1 receptor (MC1R) Arg163Gln (rs885479) and attractin (ATRN) have been indicated as potential contributors to the evolution of light skin in East Asian populations.

Tanning responseedit

Tanning response in humans is controlled by a variety of genes. MC1R variants Arg151Sys (rs1805007), Arg160Trp (rs1805008), Asp294Sys (rs1805009), Val60Leu (rs1805005) and Val92Met (rs2228479) have been associated with reduced tanning response in European and/or East Asian populations. These alleles show no signs of positive selection and only occur in relatively small numbers, reaching a peak in Europe with around 28% of the population having at least one allele of one of the variations. A study of self-reported tanning ability and skin type in American non-Hispanic Caucasians found that SLC24A5 Phe374Leu is significantly associated with reduced tanning ability and also associated TYR Arg402Gln (rs1126809), OCA2 Arg305Trp (rs1800401) and a 2-SNP haplotype in ASIP (rs4911414 and rs1015362) to skin type variation within a "fair/medium/olive" context.

Albinismedit

Oculocutaneous albinism (OCA) is a lack of pigment in the eyes, skin and sometimes hair that occurs in a very small fraction of the population. The four known types of OCA are caused by mutations in the TYR, OCA2, TYRP1, and SLC45A2 genes.