Understanding deleterious variation in wild populations

近亲繁殖衰退，即近亲繁殖后代的适应性降低，是进化和保护生物学的中心话题。然而，近亲繁殖衰退的许多方面仍然知之甚少，特别是在野外。特别是，尽管经过几十年的研究，我们仍然对物种的人口统计学历史与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。很大一部分近亲繁殖衰退被认为是由隐性有害突变导致的，这些突变在近亲繁殖后代中成为纯合子。因此，群体遗传学理论预测，近亲繁殖衰退的强度和遗传结构将取决于有害突变的总负担（“突变负荷”）和高度、中度和弱有害等位基因的频率。这些反过来又应该受到历史种群规模变化的强烈影响，如瓶颈，小种群预计清除高度有害的突变更有效地比大的s.To系统地评估人口，有害的突变和近交衰退之间的复杂的相互作用，我们将采取一种新的，比较基因组方法使用鳍足类。我们将从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开始。为此，我们将应用创新工具对来自12个物种的全基因组重测序数据进行重新测序，这些物种跨越了从极端人为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郁症的一个关键的健身性状，生存到性成熟的遗传结构的影响，在六个物种与对比histors.Finally，最近的研究预测突变负荷的基础上引发了争论的最佳遗传管理策略的小种群。因此，迫切需要通过将这些预测与自然环境中个人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繁殖导致的适应性变化的很大一部分似乎是合理的，但有几个因素可能会破坏它们的解释力，包括未能解释平衡选择下基因座上的有益等位基因。我们将使用一个鳍足类动物系统模型，南极海狗，来量化预测的个体突变负荷与其他方差分量的解释力，包括主要组织相容性复合体的超显性，这是一组免疫基因，可以解释两个相关海豹物种后代存活率差异的20-70%。我们的项目将提供系统的见解之间的相互作用的人口历史，突变负荷和健身变化在野生种群，具有重要意义的进化和保护生物学。

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.