Impacts of Neanderthal-introgressed sequences on the landscape of human gene expression
By R. McCoy, J. Wakefield, Joshua M. Akey. 2017
158 citations recorded by the source corpus.
SUMMARY 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 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.
Subfields: Genetics, Molecular Biology
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Citations in the corpus
- Aspects of human physical and behavioural evolution during the last 1 million years (2019, background): “Most Neanderthal DNA appears to have been rapidly selected away, but some of it appears to be expressed physically today, for example in traits linked with the skin and hair, the immune system, hypercoagulation and certain personality disorders (McCoy et al., 2017).”