The population genomics of sexually antagonistic variation in Drosophila

果蝇性拮抗变异的群体基因组学

• 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

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著差异，有时如此之大，以至于性别最初被描述为不同的物种。这种性别二形性根源于男性和女性生殖角色之间的差异，这些角色为每个性别选择不同的最佳形态、生理和行为。但是，尽管性别二态现象普遍存在，但它往往也是不完整的。许多种群的基因变异是“性对抗”的，即等位基因对一种性别有利，但对另一种性别有害。性别对立产生于，一方面，共享同一基因组的两个性别之间的基因耦合，另一方面，两个性别在相同特征上的相反选择的冲突。因此，选择可以在很长一段时间内在种群中保持性别对立的遗传变异。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)，在种群中很常见，对一个性别有利，但对另一个性别有害。与性别特定选择的一个鲜为人知的副产品不同，性别对抗是一种重要的进化力量。由于它们对一种性别的有害影响，性别拮抗变体会导致部分适应不良，两种性别都不会达到其最佳表型。因此，性对抗在保持适应性变异方面发挥着重要作用，包括性别特有的人类疾病等位基因。SA也是分化的性染色体进化的主要驱动力，进一步促进了性别差异。最后，SA通常是适应性冲突的模型，其中与遗传变量相关联的适应度在不同的背景下是不同的。例如，这包括生命早期有益、后来有害的等位基因，或者参与多种反应的酶的功能权衡。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影响。然而，尽管SA具有进化驱动力的基本作用，但其遗传基础及其进化动态仍未得到很好的描述。这在一定程度上是因为，从历史上看，我们对性别对抗的遗传基础了解有限。直到最近，我们才开始解决这个问题，方法是在实验室的果蝇种群中识别出数百个性别对立的变种。这是向前迈出的重要一步，并为解决我们对性别对立的理解中的许多空白和针对性别的适应的限制打开了可能性。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合度影响的问题，深入了解拮抗变体的进化动力学和翻转，并探索性拮抗在维持自然种群内遗传多样性方面所起的作用。我们将在这里回答这些问题，将复杂的计算种群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。这项工作将代表着我们在理解性别对抗的遗传学和进化方面的飞跃，以及促进和限制性别特异性适应和性别二型性进化的遗传过程。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。

项目成果

The establishment of locally adaptive inversions in structured populations

在结构化群体中建立局部自适应反转

• DOI: 10.1101/2022.12.05.519181
• 发表时间: 2022
• 作者: Mackintosh C