The MUC19 Gene: An Evolutionary History of Recurrent Introgression and Natural Selection

We study the gene MUC19, for which some modern humans carry a
Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels
with various biological functions. We find diagnostic variants for the
Denisovan-like MUC19 haplotype at high frequencies in admixed Latin
American individuals, 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 is under
positive selection and 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. Finally, some Neanderthals carry
the Denisovan-like MUC19 haplotype, and that it was likely introgressed
into human populations through Neanderthal introgression rather than
Denisovan introgression.

本研究聚焦基因MUC19，部分现代人类携带其丹尼索瓦人样单倍型（haplotype）。MUC19属于黏蛋白（mucin），是一类可形成凝胶并具备多种生物学功能的糖蛋白（glycoprotein）。我们发现，针对丹尼索瓦人样MUC19单倍型的诊断性变异位点（diagnostic variants）在混血拉丁美洲人群中呈现高频率分布，而在23例古代美洲原住民个体中频率达到峰值——这些古代个体均早于美洲人群与欧洲、非洲人群发生的遗传混合事件。我们进一步证实，该丹尼索瓦人样MUC19单倍型处于正选择（positive selection）压力之下，且其携带的30碱基对（base-pair）可变数目串联重复序列（variable number tandem repeat）的拷贝数（copy number）更高；同时该重复序列的拷贝数在美洲人群中普遍处于极高水平。此外，部分尼安德特人也携带该丹尼索瓦人样MUC19单倍型，提示该单倍型更可能通过尼安德特人基因渐渗（introgression），而非丹尼索瓦人基因渐渗的途径进入现代人类种群。