School of Biological Sciences and Centre for Geometric Biology, Monash University, Clayton 3800, VIC, Australia.
Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
Genetics. 2021 Nov 5;219(3). doi: 10.1093/genetics/iyab143.
Fitness effects of deleterious mutations can differ between females and males due to: (i) sex differences in the strength of purifying selection; and (ii) sex differences in ploidy. Although sex differences in fitness effects have important broader implications (e.g., for the evolution of sex and lifespan), few studies have quantified their scope. Those that have belong to one of two distinct empirical traditions: (i) quantitative genetics, which focusses on multi-locus genetic variances in each sex, but is largely agnostic about their genetic basis; and (ii) molecular population genetics, which focusses on comparing autosomal and X-linked polymorphism, but is poorly suited for inferring contemporary sex differences. Here, we combine both traditions to present a comprehensive analysis of female and male adult reproductive fitness among 202 outbred, laboratory-adapted, hemiclonal genomes of Drosophila melanogaster. While we find no clear evidence for sex differences in the strength of purifying selection, sex differences in ploidy generate multiple signals of enhanced purifying selection for X-linked loci. These signals are present in quantitative genetic metrics-i.e., a disproportionate contribution of the X to male (but not female) fitness variation-and population genetic metrics-i.e., steeper regressions of an allele's average fitness effect on its frequency, and proportionally less nonsynonymous polymorphism on the X than autosomes. Fitting our data to models for both sets of metrics, we infer that deleterious alleles are partially recessive. Given the often-large gap between quantitative and population genetic estimates of evolutionary parameters, our study showcases the benefits of combining genomic and fitness data when estimating such parameters.
由于以下两个原因，有害突变对雌性和雄性的适应度的影响可能不同：（i） 净化选择的强度在性别之间存在差异；以及（ii） 倍性在性别之间存在差异。尽管适应度影响的性别差异具有重要的广泛意义（例如，对性和寿命的进化），但很少有研究量化它们的范围。那些属于两个不同的经验传统之一：（i） 数量遗传学，它侧重于每个性别的多基因遗传方差，但在很大程度上对其遗传基础一无所知；以及（ii） 分子群体遗传学，它侧重于比较常染色体和 X 连锁多态性，但不适合推断当代性别差异。在这里，我们结合了这两个传统，对 202 个杂交、实验室适应的黑腹果蝇半克隆基因组的雌性和雄性成年生殖适应性进行了全面分析。虽然我们没有发现净化选择强度存在性别差异的明确证据，但倍性的性别差异产生了多个与 X 连锁基因座增强净化选择相关的信号。这些信号存在于数量遗传指标中，即 X 对雄性（而不是雌性）适应度变异的不成比例的贡献，以及群体遗传指标中，即等位基因平均适应度效应与其频率的回归更陡峭，X 染色体上的非同义多态性比例低于常染色体。我们根据这两组指标的数据拟合模型，推断有害等位基因部分是隐性的。鉴于进化参数的定量和群体遗传估计之间经常存在很大差距，我们的研究展示了在估计这些参数时结合基因组和适应性数据的好处。
