The MUC19 gene: An evolutionary history of recurrent introgression and natural selection

• 成果类型: Article
• 署名作者: Villanea, Fernando A.; Peede, David; Kaufman, Eli J.; Anorve-Garibay, Valeria; Chevy, Elizabeth T.; Villa-Islas, Viridiana; Witt, Kelsey E.; Zeloni, Roberta; Marnetto, Davide; Moorjani, Priya; Jay, Flora; Valdmanis, Paul N.; Avila-Arcos, Maria C.; Huerta-Sanchez, Emilia
• 署名单位: University of Colorado System; University of Colorado Boulder; Brown University; Brown University; Brown University; University of Washington; University of Washington Seattle; Universidad Nacional Autonoma de Mexico; University of Copenhagen; Clemson University; Clemson University; University of Padua; University of Turin; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Microsoft; Centre National de la Recherche Scientifique (CNRS); Inria; Universite Paris Saclay; Trinity College Dublin; Brown University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9723
• DOI: 10.1126/science.adl0882
• 发表日期: 2025-08-21
• 关键词: coverage neanderthal genome; adaptive introgression; positive selection; sequence; adaptation; nucleotide; polymorphisms; haplotype; inference; ancestry

摘要

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 American individuals and at highest frequency in 23 ancient Indigenous American individuals, all pre-dating 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 admixed American populations. Finally, we find that some Neanderthals carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into modern human populations through Neanderthal introgression rather than Denisovan introgression.