The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.

We study the gene MUC19, for which modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global populations, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat, and that copy numbers of this repeat are exceedingly high in American populations and are under positive selection. This study provides the first example of positive selection acting on archaic alleles at coding sites and VNTRs. Finally, we find that some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression.