Archaic adaptive introgression in modern human reproductive genes

Abstract

Modern humans and archaic hominins, namely Denisovans and Neanderthals, have a long history of admixture. Some of these admixture events have allowed modern humans to adapt to new environments outside of Africa. Little research has been done on the impact of archaic introgression on genes associated with reproduction. In this study we report evidence of adaptive introgression of 118 genes within modern humans that have been previously associated with reproduction in mice or modern humans. We identified 11 archaic core haplotypes, three that have been positively selected, with 327 archaic alleles being genome-wide significant for a variety of traits. Over 300 of these variants were discovered to be eQTLs regulating 176 genes with 81% of the archaic eQTLs overlapping a core haplotype region regulating genes expressed in reproductive tissues. Several of the adaptively introgressed genes in our results are enriched in developmental and cancer pathways, while some have been associated with embryo development and reproductive-inhibiting phenotypes like endometriosis and preeclampsia. Lastly, we find that archaic alleles overlapping an introgressed segment on chromosome 2 are protective against prostate cancer. Our results highlight that archaic alleles show connections with important developmental pathways throughout the lifespan and may help regulate these critical processes.