Human Skin Color Evolution and Adaptation

Skin Colour Evolution and Adaptation

• Human skin colour exhibits tremendous diversity across different geographical regions, influenced by environmental adaptations during human migrations.
• Skin colour is a critical and externally visible component of human phenotype, regulated by genetic interactions and environmental factors.
• The evolution of skin colour has been shaped by many genes and their interactions, as well as environmental factors combined with human migrations.

The Role of Ultraviolet Radiation (UVR)

• UVR, particularly UVB, promotes vitamin D synthesis in the body, an essential nutrient for calcium and phosphorus absorption and bone synthesis.
• Low UVR and reduced vitamin D synthesis can lead to rickets (flawed bone development) and osteomalacia (soft bone disease) in adults.
• Excessive UVR, primarily UVA, can lead to free radical oxidation of folate, resulting in its degradation. Folate is a crucial vitamin for human fertility.

Melanin and Skin Colour

• The balance between vitamin D and folate has driven the evolution of skin colour throughout human migrations.
• Melanin is a potent antioxidant and free-radical scavenger, playing a crucial role in preventing DNA damage and tumourigenesis.
• Eumelanin and pheomelanin are the two primary types of melanin, produced by melanocytes in the epidermis, responsible for variations in pigmentation, including skin and hair colour.

Genetic Basis and Adaptive Evolution of Skin Colour in African Populations

• The African continent exhibits high levels of UVR, climate, and environmental diversity, leading to variations in skin pigmentation across populations.

• Darker skin reduces the risk of DNA damage caused by UVR and the degradation of folate, offering protection against skin cancer.

• Genetic research has identified variants in or near genes strongly associated with skin pigmentation, including MFSD12, SLC24A5, PDPK1, HERC2/OCA2, MITF, and DDB1/CYB561A3/TMEM138 genes.### Melanin and Skin Pigmentation

• Melanin is responsible for a range of colors from black to brown to yellow in bird feathers and skin tissues.

• Its varied distribution determines the tinting, mottling, and reflective effects of feathers, influencing the appearance of bird features.

• Carotenoids, which come from the food birds eat, are responsible for giving feathers their distinctive red, yellow, and orange colors.

Melanosomes and Lysosomes

• Melanin is produced in melanosomes and is highly expressed in skin tissues.
• The reduction of Mfsd12 mRNA in the mouse can lead to an increase in eumelanin content, which occurs in a cell-autonomous manner.

Genetic Associations with Skin Pigmentation

• Comparative cross-species studies of humans, fish, and birds show that pigmentation can change significantly and adaptively based on ecological and social needs.
• Two SNPs, rs56203814 and rs10424065, are associated with skin pigmentation phenotypes in African populations within the MFSD12 gene.
• The ancestral allele T for both variants is exclusively found in African populations and exhibits a significant association with darker skin pigmentation.
• Two upstream SNPs, rs6510760 and rs112332856, on MFSD12 also contribute to darker skin in Africans.

Population-Specific Variants

• Table 1 lists variants associated with skin pigmentation in African, East Asian, and European populations.
• Interestingly, the frequencies of these variants differ significantly between populations.
• For example, the rs56203814 variant is found in 20.8% of Africans, but is absent in East Asians and Europeans.

Other Genes Associated with Skin Pigmentation

• Other genes associated with skin pigmentation include DDB1, HERC2, OCA2, SLC24A5, and KITLG.
• These genes are involved in various biological processes, including melanosome biogenesis, pigmentation, and skin development.
• Variants in these genes have been found to be associated with skin pigmentation phenotypes in different populations.### Skin Pigmentation and UV Exposure
• Exposure to UV radiation increases melanin production as a protective response to reduce DNA damage.
• The DNA repair mechanism involving DDB1 (DNA damage-binding protein 1) affects melanocyte functionality and melanin synthesis.

Genes Associated with Skin Pigmentation

• TYR (Tyrosinase) gene: mutations in this gene are associated with skin pigmentation in different populations (e.g. rs1042602, rs1126809, rs1393350).
• TYRP1 (Tyrosinase-related protein 1) gene: rs2733831 is associated with skin pigmentation in European populations.
• UGT1A (UDP-glucuronosyltransferase 1A) gene: rs6742078 is associated with skin pigmentation in European populations.
• DDB1 (DNA damage-binding protein 1) gene: plays a specific role in the adaptive response to high environmental pressure from UV exposure in African populations.
• TMEM138 (transmembrane protein 138) gene: located near the DDB1 gene and is associated with skin pigmentation variation.

Population Genetics and Skin Pigmentation

• Multidirectional gene flow in Africa has had a profound effect on the genetic makeup of African populations and subsequent skin pigmentation.
• The SLC24A5 gene is associated with lighter skin pigmentation in European populations and has been introduced into African populations through gene flow.
• The rs1426654 A allele in the SLC24A5 gene is associated with lighter skin pigmentation in African populations and is nearly fixed in European populations.

East Asian Populations

• East Asian populations have relatively low levels of UV radiation, which reduces the need for protective melanin, resulting in an adaptive lighter skin.
• OCA2 (Oculocutaneous albinism type 2) gene: encodes a P-protein, which is a unique 12-transmembrane transporter protein in the melanosome membrane.
• rs1800414 (His615Arg) in the OCA2 gene: is associated with lighter skin pigmentation in East Asian populations and is nearly absent in European and African populations.
• Positive selection for rs1800414-G in East Asia is thought to date back to the Late Palaeolithic period (25-30 kya).

Pigmentation Genes Across Species

• The fundamental vertebrate pathway for melanosome production is conserved across species.
• OCA2 encodes the p-protein, which is an essential component of specific Cl- ion channels in melanosome membranes.
• OCA2 affects eye and hair color in mice, and is involved in the regulation of melanin carrier differentiation in zebrafish.
• OCA2 also has a significant effect on dorsoventral color patterns and feather coloration in birds.