Tibetan Study Finds Adaptive Variant Influencing Skin Pigmentation

For a paper appearing in PNAS, a team from the Chinese Academy of Sciences, Zhengzhou University, and elsewhere explore skin pigmentation-related genetic variants that have helped Tibetan individuals from high-altitude Qinghai-Tibetan Plateau sites adapt to strong ultraviolet (UV) light exposure. With skin pigment phenotyping profiles for more than 1,830 Tibetan or Han Chinese individuals, the researchers compared pigment adaptations, bringing in available genome sequence and genotyping data to focus in on a pigmentation-associated GNPAT enhancer variant called rs75356281 that is overrepresented in Tibetan individuals but relatively rare in populations from other parts of the world. With transcriptome sequencing on several CRISPR-edited cell lines, together with protein interaction analyses, they linked the gene to pigmentation pathways, demonstrating that the representation of adaptive GNPAT alleles and other genes shift in response to UV light exposure. "We detect strong signals of positive selection on the pigmentation gene GNPAT in Tibetans," the researchers report. "The adaptive allele of the GNPAT variant rs75356281 is significantly associated with the dark skin of Tibetans, and it affects the enhancer activity of GNPAT, leading to an increased tanning ability under UV radiation."