Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies

The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual antagonism’, in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.

性二态性（sexual dimorphism）的演化受共享基因组的约束，由此产生性拮抗（sexual antagonism）——在该过程中，特定基因座上的不同等位基因在雄性和雌性中分别受到自然选择的青睐。尽管性拮抗在诸多分类群中广泛存在，但我们对拮抗遗传变异体的具体属性、基因组位置及演化动态仍知之甚少。为弥补这些研究空白，我们利用来自202株经全基因组测序的半克隆黑腹果蝇（Drosophila melanogaster）品系的性别特异性适合度数据，开展了针对性拮抗的全基因组关联分析（genome-wide association study, GWAS）。本研究共鉴定出约230个携带候选拮抗单核苷酸多态性（single nucleotide polymorphisms, SNPs）的染色体簇。与经典理论相悖的是，本研究未发现明确证据表明X染色体是性拮抗变异的热点区域。通过对拮抗SNPs进行功能表征，我们发现其中错义变异的占比显著偏高，但在基因功能类别上并未出现明显富集。此外，我们通过分析野生黑腹果蝇种群及近缘物种中现存的多态性，评估了拮抗变异的演化持久性。值得注意的是，在黑腹果蝇的整个分布范围及其姊妹物种拟暗果蝇（Drosophila simulans）中，拮抗变异均与平衡选择的多种分子特征显著相关，这表明基因组约束对性二态性演化的影响广泛且持久（持续时长约100万年）。基于本研究结果，我们提出：拮抗变异之所以积累，是因为蛋白质编码序列层面的性冲突难以被解决，这一基因组约束进而促进了可遗传适合度变异的长期维持。