School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
Proc Biol Sci. 2022 Jan 26;289(1967):20212314. doi: 10.1098/rspb.2021.2314.
Mutations with beneficial effects in one sex can have deleterious effects in the other. Such 'sexually antagonistic' (SA) variants contribute to variation in life-history traits and overall fitness, yet their genomic distribution is poorly resolved. Theory predicts that SA variants could be enriched on the X chromosome or autosomes, yet current empirical tests face two formidable challenges: (i) identifying SA selection in genomic data is difficult; and (ii) metrics of SA variation show persistent biases towards the X, even when SA variants are randomly distributed across the genome. Here, we present an unbiased test of the theory that SA variants are enriched on the X. We first develop models for reproductive -a metric for quantifying sex-differential (including SA) effects of genetic variants on lifetime reproductive success-that control for X-linked biases. Comparing data from approximately 250 000 UK Biobank individuals to our models, we find elevations consistent with both X-linked and autosomal SA polymorphisms affecting reproductive success in humans. However, the extent of elevations does not differ from a model in which SA polymorphisms are randomly distributed across the genome. We argue that the polygenic nature of SA variation, along with sex asymmetries in SA effects, might render X-linked enrichment of SA polymorphisms unlikely.
有利影响在一种性别中的突变可能在另一种性别中产生有害影响。这种“性拮抗”（SA）变体有助于生命史特征和整体适应性的变化，但它们的基因组分布还不清楚。理论预测，SA 变体可能在 X 染色体或常染色体上富集，但目前的实证测试面临两个艰巨的挑战：（i）在基因组数据中识别 SA 选择很困难；（ii）SA 变异的衡量标准仍然偏向 X，即使 SA 变体在基因组中随机分布。在这里，我们提出了一个无偏测试理论，即 SA 变体在 X 上富集。我们首先开发了生殖的模型——一种用于量化遗传变异对终生生殖成功率的性别差异（包括 SA 效应）的指标——该模型控制了 X 连锁偏倚。将来自大约 250000 名英国生物银行个体的数据集与我们的模型进行比较，我们发现 X 连锁和常染色体 SA 多态性都能显著提高人类的生殖成功率。然而，与 SA 多态性随机分布在基因组中的模型相比，这些升高的幅度并没有差异。我们认为，SA 变异的多基因性质以及 SA 效应的性别不对称性可能使 X 连锁的 SA 多态性富集不太可能。
