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.

许多物种的雄性和雌性在表型上存在显着差异，有时差异如此之大，以至于最初将性别描述为不同的物种。这种性别二态性根源于男性和女性生殖角色的差异，每种性别选择不同的最佳形态、生理和行为。但性别二态性虽然普遍存在，但也往往是不完整的。许多人群都存在“性对抗”的遗传变异，即等位基因对一种性别有利，但对另一种性别有害。性对抗一方面源于共享基因组的两种性别之间的遗传耦合的冲突，另一方面源于两种性别对同源性状的反对选择。因此，选择可以在群体中长期维持性对抗遗传变异。这些变异具有高度相关性，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，并且对一种性别有利，但对另一种性别有害。性对抗远不是性别特异性选择的一个不起眼的副产品，而是一种重要的进化力量。由于它们对一种性别的有害影响，性拮抗变异导致部分适应不良，两种性别都没有达到其最佳表型。因此，性对抗在维持适应性变异（包括性别特异性人类疾病等位基因）方面发挥着重要作用。 SA也是分化性染色体进化的主要驱动力，进一步导致性别差异。最后，SA 通常是适应性冲突的模型，其中与遗传变异相关的适应性在不同的环境中有所不同。例如，这包括在生命早期有益而以后有害的等位基因，或者参与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影响。然而，尽管 SA 具有作为进化驱动因素的基本作用，但 SA 的遗传基础及其进化动力学仍然知之甚少。部分原因是历史上我们对性对抗遗传基础的了解有限。直到最近，我们才能够通过在实验室果蝇群体中鉴定出数百种性拮抗变异来开始解决这个问题。这是向前迈出的重要一步，并为解决我们对性对抗的理解中的许多差距和性别特异性适应的局限性提供了可能性。我们现在可以询问有关野生种群中个体拮抗等位基因的适应性效应的问题，深入了解拮抗变体的进化动态和更替，并探索性对抗在维持自然种群内遗传变异中所起的作用。我们将在这里回答这些问题，将复杂的计算群体基因组学方法应用于来自世界各地的数百个果蝇基因组序列。这项工作将代表我们对性对抗的遗传学和进化以及促进性对抗的遗传过程的理解的飞跃。并限制性别特异性适应和性二态性的进化。解决这些问题的重要性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特征的动物育种者以及对维持性别特异性疾病危险因素感兴趣的生物医学研究人员相关。