title: Functional implications of Neandertal introgression in modern humans.
abstract: Admixture between early modern humans and Neandertals approximately 50,000-60,000 years ago has resulted in 1.5-4% Neandertal ancestry in the genomes of present-day non-Africans. Evidence is accumulating that some of these archaic alleles are advantageous for modern humans, while others are deleterious; however, the major mechanism by which these archaic alleles act has not been fully explored.
  
  
  
  Here we assess the contributions of introgressed non-synonymous and regulatory variants to modern human protein and gene expression variation. We show that gene expression changes are more often associated with Neandertal ancestry than expected, and that the introgressed non-synonymous variants tend to have less predicted functional effect on modern human proteins than mutations that arose on the human lineage. Conversely, introgressed alleles contribute proportionally more to expression variation than non-introgressed alleles.
  
  
  
  Our results suggest that the major influence of Neandertal introgressed alleles is through their effects on gene regulation.
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany. michael_dannemann@eva.mpg.de.
authors.forename: Michael
authors.identifier: 0000-0002-7076-8731
authors.initials: M
authors.lastname: Dannemann
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Prüfer
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany. kelso@eva.mpg.de.
authors.forename: Janet
authors.identifier: 0000-0002-3618-322X
authors.initials: J
authors.lastname: Kelso
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D015870:Gene Expression; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D005810:Multigene Family; D059125:Neanderthals / Q000235:genetics*; D010641:Phenotype
keywords: Gene expression regulation; Human evolution; Neandertal introgression; Protein sequence variation