RT Journal Article
SR Electronic
T1 Denisovan introgression has shaped the immune system of present-day Papuans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.09.196444
DO 10.1101/2020.07.09.196444
A1 Davide M. Vespasiani
A1 Guy S. Jacobs
A1 Nicolas Brucato
A1 Murray P. Cox
A1 Irene Gallego Romero
YR 2020
UL http://biorxiv.org/content/early/2020/07/09/2020.07.09.196444.abstract
AB Modern humans have substantially admixed with multiple archaic hominins. New Guineans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals, whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these events remain poorly understood. Here we investigate the function of archaic alleles of both Denisovan and Neanderthal ancestry characterised within a previously published set of 72 genomes from individuals of Papuan genetic ancestry living in the island of New Guinea. By comparing the distribution of archaic and modern human variants, we are able to assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We find that archaic alleles are often located within cis-regulatory elements and transcribed regions of the genome, suggesting that they are actively involved in a wide range of cellular regulatory processes. We identify 39,954 high-confidence Denisovan variants that fall within annotated cis-regulatory elements and have the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes in present-day humans. Additionally, we detect a consistent signal across Denisovan variants of strong involvement in immune-related processes. Lastly, we show how such regulatory effects might underlie some of the observed gene expression differences between multiple Indonesian populations carrying varying amount of Denisovan DNA. Together, these data provide support for the hypothesis that, despite their broadly deleterious nature, archaic alleles actively contribute to modern human phenotypic diversity and might have facilitated early adaptation to non-African environments.Competing Interest StatementThe authors have declared no competing interest.