The population genomics of sexually antagonistic variation in Drosophila

许多物种的雄性和雌性在表型上存在显著差异，有时差异如此之大，以至于两性最初被描述为不同的物种。这种两性二态性的根源在于男性和女性生殖角色的差异，这种差异选择了不同性别的最佳形态、生理和行为。但是，尽管两性二态性无处不在，但它也常常是不完整的。许多种群拥有“性拮抗”的基因变异，即等位基因对一种性别有益，但对另一种性别有害。性别对抗产生于两种冲突，一方面是共享基因组的两性之间的遗传偶联，另一方面是两性在同源性状上的对立选择。因此，选择可以在种群中长时间维持性拮抗的遗传变异。这些变异是高度相关的，因为它们在功能上很重要（毕竟，它们影响健康），在人群中很常见，对一种性别有益，对另一种性别有害。性别对抗绝不是性别特异性选择的模糊副产品，而是一种重要的进化力量。由于它们对一个性别的有害影响，性拮抗变异导致部分不适应，两种性别都无法达到最佳表型。因此，性拮抗在维持适应度变异（包括性别特异性人类疾病等位基因）中起着重要作用。SA也是分化性染色体进化的主要驱动因素，进一步促进了性别差异。最后，SA是一般适应性冲突的模型，其中与遗传变异相关的适应度在不同的环境中是不同的。例如，这包括在生命早期有益而在生命后期有害的等位基因，或者涉及多种反应的酶的功能权衡。因此，SA的研究具有从性别差异和基因组结构到人类衰老和健康的意义。然而，尽管其作为进化驱动因素的基本作用，SA的遗传基础及其进化动力学仍然缺乏特征。这部分是因为历史上我们对性对抗的遗传基础的信息有限。直到最近，我们才开始解决这个问题，在实验室的果蝇种群中识别出数百种性拮抗变异。这是向前迈出的重要一步，并为解决我们对性别对抗和性别特异性适应的局限性的理解中的许多空白提供了可能性。我们现在可以提出关于野生种群中个体拮抗等位基因的适应度效应的问题，深入了解拮抗变异的进化动力学和转换，并探索性拮抗在维持自然种群遗传变异中的作用。我们将在这里回答这些问题，应用复杂的计算种群基因组学方法对来自世界各地的数百个果蝇基因组序列进行分析。这项工作将代表我们对性别对抗的遗传学和进化，以及促进和限制性别特异性适应和两性二态进化的遗传过程的理解的飞跃。解决这些问题远远超出了进化遗传学领域，我们的结果将与旨在改善性别特异性性状的动物育种者和对维持性别特异性疾病风险因素感兴趣的生物医学研究人员相关。

Males and females of many species differ significantly in phenotype, sometimes so much so that the sexes were initially described as different species. Such sexual dimorphism is rooted in the differences between male and female reproductive roles, which select for different optimal morphologies, physiologies and behaviours in each sex. But while ubiquitous, sexual dimorphism is also often incomplete. Many populations harbour genetic variation that is 'sexually antagonistic', where alleles are beneficial to one sex but detrimental to the other. Sexual antagonism arises from the conflict of, on the one hand, genetic coupling between two sexes that share a genome and, on the other hand, opposing selection in the two sexes on homologous traits. As a result selection can maintain sexually antagonistic genetic variants in the population for prolonged periods of time. These variants are highly relevant because they are functionally important (after all, they affect fitness), are common in the population and benefit one sex while harming the other.Far from an obscure by-product of sex-specific selection, sexual antagonism is an important evolutionary force. Due to their deleterious effects in one sex, sexual antagonistic variants result in partial maladaptation, with neither of the two sexes attaining its optimal phenotype. Sexual antagonism thus plays an important role in the maintenance of fitness variation, including sex-specific human disease alleles. SA is also a major driver in the evolution of differentiated sex chromosomes, further contributing to sex differences. And finally, SA is as model for adaptive conflicts in general, where the fitness associated with a genetic variant differs in different contexts. This includes, for example, alleles that are beneficial early in life and deleterious later on, or functional trade-offs in enzymes that are involved in multiple reactions. The study of SA thus has implications that go from sex differences and genome structure to human ageing and health. Yet, despite its fundamental role as an evolutionary driver, the genetic bases of SA and its evolutionary dynamics remain poorly characterised. This is partly because historically we had limited information about the genetic basis of sexual antagonism. Only recently were we able to start solving this problem by identifying hundreds of sexually antagonistic variants in a laboratory population of fruit flies. This was a significant step forward and has opened the possibility to address the many gaps in our understanding of sexual antagonism and the limits to sex-specific adaptation. We can now ask questions about the fitness effects of individual antagonistic alleles in wild populations, gain insights into the evolutionary dynamics and turn-over of antagonistic variants, and explore the role that sexual antagonism plays in maintaining genetic variation within natural populations. We will answer these questions here, applying sophisticated computational population genomics approaches to hundreds of Drosophila genome sequences from around the world.This work will represent a leap forward in our understanding of the genetics and evolution of sexual antagonism, and of the genetic processes that promote and limit sex-specific adaptation and the evolution of sexual dimorphism. Addressing these questions matters well beyond the field of evolutionary genetics, and our results will be relevant to animal breeders aiming to improve sex-specific traits, and biomedical researchers interested in the maintenance of risk factors for sex-specific disease.