SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans

Abstract

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.

Admixture as the basis for genetic mapping

“…These studies have identified several genes associated with skin pigmentation that displayed genetic signatures consistent with divergent positive selection [33,34] and with recent convergent evolution of a lighter pigmentation type in Europeans and East Asians [34]. Remarkably, variation at two of these loci is also responsible for pigment variation in the scales of fish [32,33].…”

“…However, multiple studies have identified genetic variants associated with lighter and darker skin pigmentation in humans [32][33][34], a trait that might be differentially selected in regions with low and high ultraviolet radiation (UVR), owing to known associations between skin pigmentation and vitamin D synthesis and protection from UVR [34,35]. These studies have identified several genes associated with skin pigmentation that displayed genetic signatures consistent with divergent positive selection [33,34] and with recent convergent evolution of a lighter pigmentation type in Europeans and East Asians [34].…”

Gene–gene interactions contribute to eye colour variation in humans

“…9 Several genes were associated with various pigment traits long before the genome-wide association study era. [10][11][12][13][14][15][16] However, it is important to note that-unlike in the case of testing for many complex diseases 17 genome-wide association study has been particularly effective in association testing for human pigmentation and has confirmed already known, and revealed multiple new polymorphisms and loci involved in determination of human pigmentation. [18][19][20][21] This has been particularly striking in the case of variation in eye colour, which is assessed to be 50% explained by known polymorphisms.…”

Nous sommes tous de « race » africaine !

“…pour défi-nir les races. On sait par exemple que plusieurs gènes différents contribuent à une peau claire, SLC24A5 est celui qui est trouvé chez la majorité des Européens, mais n'est pas le seul [7]. La mutation de ce gène, impliquée dans la peau claire des Européens, est apparue récemment, il y a environ 7 000 ans ; auparavant, les populations européennes avaient la peau noire [8].…”