NEW YORK (GenomeWeb) – A genome-wide association study of Latin Americans has uncovered novel loci lined to skin pigmentation. The study also pointed to the convergent evolution of lighter skin color among Eurasians.
The analysis examined skin pigmentation and eye color among more than 6,000 Latin Americans, who broadly have a combination of African, European, and Native American ancestry. Native Americans are closely related genetically to East Asians, as the Americas were settled by people migrating from Eastern Siberia some 15,000 to 20,000 years ago.
Through their GWAS, researchers from University College London and elsewhere uncovered a dozen genomic regions associated with either skin or eye pigmentation. As they reported in Nature Communications yesterday, the researchers homed in on a strong association with a missense variant in the gene MFSD12 that is common only among Native Americans and East Asians, suggesting it was under selection in East Asians after their split from Europeans.
"It is commonly thought that variation in pigmentation, such as skin color, in Latin Americans primarily arises due to people's varying degree of European or African ancestry," co-lead author Javier MendozaRevilla from the UCL Genetics Institute said in a statement. "But our new study shows that there is variation inherited from their Native ancestors as well."
For their study, the researchers drew upon the CANDELA (Consortium for the Analysis of the Diversity of Evolution of Latin America) cohort, which includes individuals from Brazil, Colombia, Chile, Mexico, and Peru. For each of the 6,357 individuals, the researchers collected skin, hair, and eye pigmentation measures through, for instance, reflectometry. They noted that lighter pigmentation measures were correlated with each other as well as with genetic measures of European ancestry.
These individuals also underwent genotyping at more than 670,000 SNPs, and the researchers linked SNPs at 12 genomic regions to pigmentation. Skin pigmentation was associated with SNPs in eight genomic regions, five of which had been tied to skin pigmentation in previous studies of Europeans or East Asians. One of the loci had been linked to skin pigmentation in a recent study of Africans, and another had not before been reported.
Meanwhile, eye pigmentation was linked to SNPs in four regions, three of which had not been reported before.
In particular, the researchers uncovered multiple signals of association that they traced to the GRM5/TYR and OCA2/HERC2 gene regions. But they also found a strong association with the MFSD12 gene. Variants there have been linked to skin pigmentation among sub-Saharan Africans. The index SNP uncovered here, though, leads to a substitution of tyrosine for histidine that is common among East Asians and Native Americans but is rare among other populations.
Functional studies indicated that MFSD12 is involved in lysosomal biology and can affect skin pigmentation in animal models. It is further typically expressed in melanocytes of the epidermis, but not within hair bulb melanocytes or scalp follicles.
The researchers noted that of the five regions they newly linked to pigmentation, three showed strong signals of selection. The strongest, they noted, was in the MFSD12 gene region among East Asians. In addition, allele frequencies of four SNPs, including the index SNP at MFSD12, exhibited a significant correlation with solar radiation.
They estimated that selection at this region began about 10,834 years ago, after the ancestors of East Asians and Europeans split off from one another. It also suggests that lighter skin pigmentation is a convergent evolution trait among Eurasians, the researchers added.
"Our work demonstrates that lighter skin color evolved independently in Europe and East Asia," co-first author Kaustubh Adhikari from the UCL Genetics Institute said in a statement. "We also show that this gene was under strong natural selection in East Asia, possibly as adaptation to changes in sunlight levels and ultraviolet radiation."