RT Journal Article
SR Electronic
T1 Neanderthal introgression reintroduced functional alleles lost in the human out of Africa bottleneck
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 533257
DO 10.1101/533257
A1 David C. Rinker
A1 Corinne N. Simonti
A1 Evonne McArthur
A1 Douglas Shaw
A1 Emily Hodges
A1 John A. Capra
YR 2019
UL http://biorxiv.org/content/early/2019/01/29/533257.abstract
AB Neanderthal ancestry remains across modern Eurasian genomes, and introgressed sequences influence diverse phenotypes, including immune, skin, and neuropsychiatric diseases. Interpretation of introgressed sequences has focused on alleles derived in the Neanderthal lineage. Here, we demonstrate that Neanderthal introgression also reintroduced thousands of ancestral hominin alleles lost in the Eurasian out of Africa bottleneck. Combining evolutionary simulations, expression quantitative trait loci (eQTL), massively parallel reporter assay (MPRA) data, and in vitro validation, we show that reintroduced alleles (RAs) have different fitness effects than Neanderthal-derived alleles (NDAs) and that some RAs regulate gene expression independent of NDAs. Illustrating the broad potential influence of RAs, we find that over 70% of known phenotype associations with NDAs are equally associated with RAs. Finally, we discover enrichment for RA eQTL activity in several tissues, with strongest enrichment in the brain. In summary, our study reveals that Neanderthal introgression supplied Eurasians with many lost functional variants and demonstrates that RAs must be considered when evaluating the effects of introgression.ONE SENTENCE SUMMARY Neanderthal interbreeding with modern humans restored to Eurasians, hundreds of thousands of ancient alleles that were lost in the out of Africa bottleneck.