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Sex-biased reduction in reproductive success drives selective constraint on human genes

By Eugene J Gardner, Matthew D.C. Neville, Kaitlin E Samocha, Kieron Barclay, Martin Kolk, Mari EK Niemi, George Kirov, Hilary C Martin, Matthew E Hurles

Posted 28 May 2020
bioRxiv DOI: 10.1101/2020.05.26.116111

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.

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