Functional implications of Neandertal introgression in modern humans

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: Our results suggest that the major influence of Neandertal introgressed alleles is through their effects on gene regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1181-7) contains supplementary material, which is available to authorized users.