PT  - JOURNAL ARTICLE
AU  - Eugene J. Gardner
AU  - Matthew D. C. Neville
AU  - Kaitlin E. Samocha
AU  - Kieron Barclay
AU  - Martin Kolk
AU  - Mari E. K. Niemi
AU  - George Kirov
AU  - Hilary C. Martin
AU  - Matthew E. Hurles
TI  - Sex-biased reduction in reproductive success drives selective constraint on human genes
AID  - 10.1101/2020.05.26.116111
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.26.116111
4099  - http://biorxiv.org/content/early/2020/12/08/2020.05.26.116111.short
4100  - http://biorxiv.org/content/early/2020/12/08/2020.05.26.116111.full
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.