小柯机器人

近日，英国威康桑格研究所Matthew E. Hurles及其研究小组发现，生殖成功率的降低与人类基因的选择约束有关。这一研究成果于2022年3月23日在线发表在国际学术期刊《自然》上。

据研究人员介绍，人类群体的全基因组测序显示，在作用于破坏性基因变体的净化选择的强度方面，各基因之间存在很大的差异。虽然在最强的选择约束下的基因与孟德尔疾病的关联高度丰富，但这些基因大多与疾病无关，因此作用于它们的选择的性质并不清楚。

研究人员表明，损害这些基因的遗传变异与生殖成功率明显降低有关，主要是由于无子化的增加，对男性的影响比对女性更强。研究人员提出的证据表明，无子化的增加可能是由与遗传相关的认知和行为特征所介导的，这可能意味着男性携带者不太可能找到生殖伴侣。这种生殖成功率的降低可能占到针对消减蛋白质编码基因的杂合变体的净化选择的20%。尽管这种遗传关系可能只占无子女总体可能性的很小一部分（不到1%），特别是与更有影响力的社会人口因素相比，它可能影响基因的长期演化。

附：英文原文

Title: Reduced reproductive success is associated with selective constraint on human genes

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

Issue&Volume: 2022-03-23

Abstract: Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants1. 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 known2. 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. Human genetic variants that impair genes that are intolerant of damaging genetic variation are associated with lower reproductive success that is probably mediated by genetically associated cognitive and behavioural traits, particularly in males.

DOI: 10.1038/s41586-022-04549-9

Source: https://www.nature.com/articles/s41586-022-04549-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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