A few years ago, a new paper, SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans, made some waves. It used zebrafish to elucidate the genetics of a locus, SLC24A5, which is responsible for 1/3 of the between population difference between Europeans and Africans in skin color. In short, Europeans are fixed for a derived variant, and Africans and East Asians for an ancestral one. Additionally, SLC24A5 shows up in tests for very recent (last 10,000 years) selection, and is implicated in 1/3 of the skin color variation in South Asians. Today, a similar paper which focuses on KITLG, cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans:
Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations…In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans.
The authors show that KITLG is a QTL of major effect across a range of species in pigment variation, and explore the molecular genetics of why this might be in sticklebacks. They also note that in humans KITLG seems to be subject to selection in both Europeans and Africans. They used an African American population to explore KITLG‘s affect on skin color:
Individuals with two African alleles (AA), one African and one European allele (AG), or two European alleles (GG) show mean M index scores of 55.2, 50.9, and 48.8, respectively. The regression coefficient, β, representing the average amount the M index decreases when one A allele is added to the model, is 3.8 melanin index units. Although these data suggest a model for the mode of inheritance that is between an additive model and a dominant model, a much larger sample size is needed to have sufficient statistical power to contrast these models.
The combined results suggest that replacement of two West African alleles with two European alleles at the KITLG locus lightens a person’s color by an average of 6 to 7 melanin units. This compares with an overall skin reflectance difference of approximately 30 melanin units between West Africans and Europeans….
This isn’t the only affect of KITLG necessarily, like many pigmentation genes there are likely other affects:
Furthermore, Kitlg plays a physiological role in the adult mammalian brain. Kitlg mutant mice have defects in spatial learning, a phenotype proposed to be due to the Kitlg expression domain in the adult hippocampus…These spatial learning defects in Kitlg mutant mice are intriguing in light of our results, which show that in the brain, the divergent Paxton-benthic-like Kitlg variant is expressed at higher levels than a marine allele. Previous studies have shown that benthic sticklebacks have increased spatial learning abilities relative to fish living in open water environments….
Obviously I’ll be believe it when I see it when it comes to humans, but, we do know of one other affect of KITLG, “…a variant near KITLG is associated with hair color.” Specifically blonde vs. brown hair. It seems that KITLG is like OCA2, there is a influence on skin color variation, but also another trait (in OCA2‘s case that’s eye color).
Related: Here are my posts on skin color and eye color.