Understanding deleterious variation in wild populations

了解野生种群的有害变异

• 批准号: 497640428
• 负责人: Professor Dr. Joseph Hoffman
• 金额: --
• 依托单位: Arbeitsgruppe Verhaltensforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/497640428?language=en
• 关键词: Understanding; deleterious; variation; wild; populations

Inbreeding depression, the reduced fitness of offspring born to closely related parents, is a central topic in evolutionary and conservation biology. However, many aspects of inbreeding depression remain poorly understood, especially in the wild. In particular, despite decades of research, we still know little about the interplay between a species’ demographic history and the strength and genetic architecture of inbreeding depression.A substantial proportion of inbreeding depression is believed to result from recessive deleterious mutations that become homozygous in inbred offspring. Accordingly, population genetic theory predicts that the strength and genetic architecture of inbreeding depression will depend on the total burden of deleterious mutations (‘mutation load’) and on the frequencies of highly, moderately and weakly deleterious alleles. These should in turn be strongly influenced by historical population size changes such as bottlenecks, as small populations are expected to purge highly deleterious mutations more efficiently than large ones.To systematically evaluate the complex interplay between demography, detrimental mutations and inbreeding depression, we will take a novel, comparative genomic approach using pinnipeds. We will start by evaluating how long-term effective population sizes and recent bottlenecks have shaped genomic landscapes of deleterious variation. For this, we will apply innovative tools to whole genome resequencing data from 12 species spanning a demographic continuum from extreme anthropogenic bottlenecks to long-term stability. From there, we will elucidate the impact of recent bottlenecks on the strength and genetic architecture of inbreeding depression for a key fitness trait, survival to sexual maturity, across six species with contrasting histories.Finally, recent studies based on predicted mutation loads have ignited debate over the best genetic management strategies for small populations. Consequently, there is a pressing need to validate these predictions by linking them to the fitness of individuals in their natural environment. While it may seem reasonable to assume that predicted damaging mutations will explain a large proportion of the variation in fitness due to inbreeding, several factors may undermine their explanatory power, including the failure to account for beneficial alleles at loci under balancing selection. We will use a model pinniped system, the Antarctic fur seal, to quantify the explanatory power of predicted individual mutation loads in relation to other variance components including overdominance at the major histocompatibility complex, a cluster of immune genes that explains 20–70% of the variance in offspring survival in two related seal species.Overall, our project will deliver systematic insights into the interplay between demographic history, mutation loads and fitness variation in wild populations, with important implications for evolutionary and conservation biology.

近亲繁殖抑制，即亲缘关系密切的父母所生后代的健康状况降低，是进化和保护生物学的一个中心话题。然而，近亲繁殖抑制的许多方面仍然知之甚少，特别是在野外。特别是，尽管进行了几十年的研究，我们仍然对一个物种的人口学历史和近亲繁殖衰退的强度和遗传结构之间的相互作用知之甚少。近亲繁殖衰退的相当大一部分被认为是由近亲繁殖后代中变成纯合的隐性有害突变造成的。因此，群体遗传学理论预测，近亲交配抑郁的强度和遗传结构将取决于有害突变的总负担(突变负载)以及高度、中等和弱有害等位基因的频率。这反过来又会受到历史种群规模变化(如瓶颈)的强烈影响，因为较小的种群预计会比较大的种群更有效地清除高度有害的突变。为了系统地评估人口统计学、有害突变和近亲繁殖抑制之间的复杂相互作用，我们将采用一种新颖的比较基因组方法，使用管脚类动物。我们将首先评估长期有效的种群规模和最近的瓶颈如何塑造有害变异的基因组景观。为此，我们将应用创新工具对12个物种的全基因组重新测序数据，从极端的人类瓶颈到长期稳定的人口连续体。从那里，我们将阐明最近的瓶颈对近亲繁殖抑制的强度和遗传结构的影响，这是一种关键的适应性状，即存活到性成熟，涉及六个历史不同的物种。最后，最近基于预测的突变负载的研究引发了关于小种群最佳遗传管理策略的辩论。因此，迫切需要通过将这些预测与个人在其自然环境中的适应性联系起来来验证这些预测。虽然假设预测的破坏性突变将解释近亲交配造成的适合度差异的很大一部分似乎是合理的，但有几个因素可能会削弱它们的解释能力，包括未能解释平衡选择下的基因座上的有益等位基因。我们将使用一个模式鳍足系统，南极毛海豹，来量化预测的个体突变负载相对于其他变异成分的解释能力，包括主要组织相容性复合体的超显性，这是一组免疫基因，解释了两个相关海豹物种后代存活率的20%-70%的差异。总而言之，我们的项目将提供系统的见解，揭示人口历史、突变负载和野生种群适应度变化之间的相互作用，对进化和保护生物学具有重要意义。