Impacts of Neanderthal-Introgressed Sequences on the Landscape of Human Gene Expression

Bibliographic Collection: 
Publication Type: Journal Article
Authors: McCoy, Rajiv C.; Wakefield, Jon; Akey, Joshua M.
Year of Publication: 2017
Journal: Cell
Volume: 168
Issue: 5
Pagination: 916 - 927.e12
Date Published: 2017/2/23
Publication Language: eng
ISBN Number: 0092-8674
Keywords: allele-specific expression, archaic hominin, Evolution, Gene Flow, gene regulation, introgression, RNA-seq

Regulatory variation influencing gene expression is a key contributor to phenotypic diversity, both within and between species. Unfortunately, RNA degrades too rapidly to be recovered from fossil remains, limiting functional genomic insights about our extinct hominin relatives. Many Neanderthal sequences survive in modern humans due to ancient hybridization, providing an opportunity to assess their contributions to transcriptional variation and to test hypotheses about regulatory evolution. We developed a flexible Bayesian statistical approach to quantify allele-specific expression (ASE) in complex RNA-seq datasets. We identified widespread expression differences between Neanderthal and modern human alleles, indicating pervasive cis-regulatory impacts of introgression. Brain regions and testes exhibited significant downregulation of Neanderthal alleles relative to other tissues, consistent with natural selection influencing the tissue-specific regulatory landscape. Our study demonstrates that Neanderthal-inherited sequences are not silent remnants of ancient interbreeding but have measurable impacts on gene expression that contribute to variation in modern human phenotypes.

Short Title: Cell