title: Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments.
abstract: As modern humans dispersed from Africa throughout the world, they encountered and interbred with archaic hominins, including Neanderthals and Denisovans [1, 2]. Although genome-scale maps of introgressed sequences have been constructed [3-6], considerable gaps in knowledge remain about the functional, phenotypic, and evolutionary significance of archaic hominin DNA that persists in present-day individuals. Here, we describe a comprehensive set of analyses that identified 126 high-frequency archaic haplotypes as putative targets of adaptive introgression in geographically diverse populations. These loci are enriched for immune-related genes (such as OAS1/2/3, TLR1/6/10, and TNFAIP3) and also encompass genes (including OCA2 and BNC2) that influence skin pigmentation phenotypes. Furthermore, we leveraged existing and novel large-scale gene expression datasets to show many positively selected archaic haplotypes act as expression quantitative trait loci (eQTLs), suggesting that modulation of transcript abundance was a common mechanism facilitating adaptive introgression. Our results demonstrate that hybridization between modern and archaic hominins provided an important reservoir of advantageous alleles that enabled adaptation to out-of-Africa environments.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gittelman
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Schraiber
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vernot
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mikacenic
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Wurfel
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: akeyj@uw.edu.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D004247:DNA / Q000235:genetics*; D003710:Demography; D005786:Gene Expression Regulation; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D059125:Neanderthals; D010858:Pigmentation
chemical_list: D004247:DNA
keywords: Denisovan; Hybridization; Neandertal; adaptive; admixture; human evolution; introgression