The population genomics of sexually antagonistic variation in Drosophila

果蝇性拮抗变异的群体基因组学

基本信息

批准号：
BB/W007703/1
负责人：
Max Reuter
金额：
$ 56.98万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW007703%2F1
关键词：
population genomics sexually antagonistic variation

项目摘要

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.

许多物种的男性和女性在表型中有显着差异，有时如此之多，以至于性别最初被描述为不同的物种。这种性二态性植根于男性和女性生殖角色之间的差异，这些角色选择了每种性别的不同最佳形态，生理和行为。但是，尽管无处不在，但性二态性也常常不完整。许多人群具有“性拮抗性”的遗传变异，这些等位基因对一种性别有益，但对另一种性别有害。性拮抗作用源于两种共享基因组的性别之间的遗传耦合的冲突，另一方面，在同源性状上的两个性别中反对选择。结果，选择可以长时间维持人口中的性拮抗遗传变异。这些变体具有很高的相关性，因为它们在功能上很重要（毕竟，它们会影响健康），在人群中很常见，并且使一种性别受益，同时损害了另一种性别。从性别特定选择的晦涩的副产品中，性拮抗作用是重要的进化力量。由于它们在一种性别中的有害作用，性拮抗变体会导致部分疾病，因为两个性别都没有达到其最佳表型。因此，性拮抗作用在维持适应性变异（包括性别特定的人类疾病等位基因）中起着重要作用。 SA还是分化性染色体演变的主要驱动力，进一步导致了性别差异。最后，SA是通常的自适应冲突的模型，在不同的情况下，与遗传变异相关的适应性在不同的情况下有所不同。例如，这包括等位基因在生命的早期和以后有害的等位基因，或在涉及多种反应的酶中的功能权衡。因此，对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含义。然而，尽管它是进化驱动力的基本作用，但SA的遗传基础及其进化动力学的特征仍然很差。这部分是因为从历史上讲，我们对性拮抗的遗传基础有限。直到最近，我们才能够通过在实验室的水果蝇种群中识别数百种性拮抗变体来开始解决这个问题。这是向前迈出的重要一步，并为解决我们对性拮抗的理解以及对性别特定适应的局限性的差距开辟了可能性。现在，我们可以询问有关野生种群中各个拮抗剂等位基因的适应性影响的问题，对拮抗变异的进化动态和转折的见解，并探讨性拮抗作用在自然种群中维持遗传变异方面的作用。我们将在这里回答这些问题，将复杂的计算人群基因组学方法应用于来自世界各地的数百种果蝇基因组序列。这项工作将代表我们对性拮抗作用的遗传学和遗传过程的理解，以及促进和限制性别适应和性型多态的进化的遗传过程的跨越。解决这些问题的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有关，以及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。