Reduced reproductive success is associated with selective constraint on human genes.

Autor: Gardner EJ; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK.; Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK., Neville MDC; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK., Samocha KE; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK., Barclay K; Max Planck Institute for Demographic Research, Rostock, Germany.; Demography Unit, Department of Sociology, Stockholm University, Stockholm, Sweden.; Swedish Collegium for Advanced Study, Uppsala, Sweden., Kolk M; Demography Unit, Department of Sociology, Stockholm University, Stockholm, Sweden., Niemi MEK; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK., Kirov G; Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK., Martin HC; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK., Hurles ME; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK. meh@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Mar; Vol. 603 (7903), pp. 858-863. Date of Electronic Publication: 2022 Mar 23.
DOI: 10.1038/s41586-022-04549-9
Abstrakt: Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants 1 . Although genes under the strongest selective constraint are highly enriched for associations with Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known 2 . Here we show that genetic variants that damage these genes are associated with markedly reduced reproductive success, primarily owing to increased childlessness, with a stronger effect in males than in females. We present evidence that increased childlessness is probably mediated by genetically associated cognitive and behavioural traits, which may mean that male carriers are less likely to find reproductive partners. This reduction in reproductive success may account for 20% of purifying selection against heterozygous variants that ablate protein-coding genes. Although this genetic association may only account for a very minor fraction of the overall likelihood of being childless (less than 1%), especially when compared to more influential sociodemographic factors, it may influence how genes evolve over time.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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