RT Journal Article SR Electronic T1 Sex-biased reduction in reproductive success drives selective constraint on human genes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.26.116111 DO 10.1101/2020.05.26.116111 A1 Eugene J. Gardner A1 Matthew D. C. Neville A1 Kaitlin E. Samocha A1 Kieron Barclay A1 Martin Kolk A1 Mari E. K. Niemi A1 George Kirov A1 Hilary C. Martin A1 Matthew E. Hurles YR 2020 UL http://biorxiv.org/content/early/2020/12/08/2020.05.26.116111.abstract AB Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants. While genes under the strongest selective constraint are highly enriched for Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known. Here we show that genetic variants that damage these genes reduce reproductive success substantially in males but much less so in females. We present evidence that this reduction is mediated primarily by cognitive and behavioural traits, which renders male carriers of such variants less likely to find mating partners. These findings represent strong genetic evidence that sexual selection mediated through female mate choice is shaping the gene pool of contemporary human populations. Furthermore, these results suggest that sexual selection accounts for 21% of purifying selection against heterozygous variants that ablate protein-coding genes.Competing Interest StatementM.E.H. is a co-founder of, consultant to, and holds shares in, Congenica Ltd, a genetics diagnostic company.