The role of structural variants in rapid adaptation

野生物种正受到来自一系列不同威胁的越来越大的压力。其中包括气候变化造成的气温升高以及全球贸易和旅行造成的新的害虫和疾病。世界各地的许多树木目前面临着这样的威胁，导致它们变得紧张，使它们无法发挥我们都受益的功能，例如捕获和储存二氧化碳或通过减少地表水径流来减少洪水风险。最终，无法科普这些威胁的个体将衰退和死亡，这不仅会使整个树种处于危险之中，还会使依赖这些物种的相关生物多样性处于危险之中。然而，尽管是大型且通常寿命长的生物体，但我们知道树种具有快速适应环境中新挑战的潜力。个体DNA之间的巨大差异，结构变异，可能对快速适应特别重要，因为它们可能导致比DNA小变化更显著的表型变化。直到最近，人们才能在种群水平上正确评估SV对遗传适应的贡献-基因组测序和分析方法的进步意味着现在可以实现这一雄心勃勃的目标。该项目将研究结构变异是否在物种如何能够快速适应新威胁方面发挥关键作用。为了验证这一点，我们将使用灰顶枯病（ADB）的情况下，在英国本土人口的欧洲灰，这提供了一个特殊的机会来分析基因组的变化参与进化的反应，新施加的压力来源。欧洲白蜡树是英国最常见的林地树木之一，在过去的十年里，遭受了导致ADB的入侵真菌的严重破坏。虽然大多数灰一旦感染疾病最终死亡，但一小部分个体具有抵抗力，即使被患病和垂死的树木包围也能保持健康。我们将对多个英国白蜡树自然种群进行采样，其中既有亚洲开发银行流行病之前的健康和患病成年人，也有自疾病到来以来建立的健康和患病青少年。我们将对每个种群的数百名个体进行全基因组测序，并对他们的抗病水平进行评分。使用这些数据，首先，我们将测试SV和ADB抗性之间的关联，以估计SV对抗性的相对贡献，与单核苷酸变异（SNP）相比。对于与抗性显著相关的SV或SNP，我们将测试每个群体中世代之间的等位基因频率变化，并分析这是否与年轻群体对ADB的抗性增加有关-这是该物种开始适应该疾病的标志。这将使我们能够确定SV对于持续适应的相对重要性。然后，我们将研究疾病压力和SV形成率之间的关系。压力可能会刺激SV形成率的提高，通过将更多的适应性突变暴露于选择，可以为快速适应性进化提供途径。最后，我们将确定基因组数据是否可以用于预测对疾病具有最大抵抗力的个体的准确性。（基因组预测）可以通过并入关于SV的信息来显著改进。通过推进对SV在适应性进化中的作用的理解以适应新施加的选择压力，并且通过开发用于改进基因组预测的有效策略，该项目还将提高我们预测哪些人最有可能在未来的威胁中幸存下来的能力，并有助于为管理自然种群以提高复原力和保护生物多样性的行动提供信息。

Wild species are under growing pressure from a range of different threats. These include increased temperatures as a result of climate change and new pests and diseases arriving as a consequence of global trade and travel. Many trees around the world currently face such threats, causing them to become stressed and rendering them less able to perform functions that we all benefit from, such as capturing and storing carbon dioxide or reducing flooding risk by decreasing surface water run-off. Ultimately, individuals that are unable to cope with these threats will decline and die, which can not only place whole tree species at risk but also the associated biodiversity that depends on these species. However, despite being large and often long-lived organisms, we know that tree species have the potential to adapt quickly to new challenges in their environment. Large differences between the DNA of individuals, structural variants, may be particularly important for rapid adaptation because they can result in more dramatic changes in phenotype than is the case for small changes to DNA. Until recently it has not been possible to properly evaluate the contribution of SVs to genetic adaptation at the population level - advances in genome sequencing and analysis methods mean this ambitious goal can now be pursued.This project will look at whether structural variants play a key role in how species are able to rapidly adapt to new threats. To test this, we will use the case of ash dieback disease (ADB) in native UK populations of European ash, which presents an exceptional opportunity to analyse the genomic changes involved in evolutionary response to newly imposed sources of stress. The European ash tree is one of the most common woodland trees in the UK and, in last ten years, has suffered severe damage from the invasive fungus that causes ADB. Although most ash eventually die once they are infected with the disease, a small percentage of individuals are resistant and remain healthy even when surrounded by diseased and dying trees. We will sample multiple natural UK populations of ash trees where both healthy and diseased adults that predate the ADB epidemic and healthy and diseased juveniles that established since the disease arrived are present. We will perform whole genome sequencing for hundreds of individuals from each population and also score them for their level of resistance to the disease. Using these data, first we will test for associations between SVs and resistance to ADB to estimate the relative contribution of SVs to resistance, compared with that of single nucleotide variants (SNPs). For SVs or SNPs significantly associated with resistance, we will test for allele frequency shifts between generations in each population and analyse if this is associated with increased resistance to ADB among the younger cohort - a sign that the species is starting to adapt to the disease. This will allow us to establish the comparative importance of SVs for ongoing adaptation. We will then examine the relationship between disease pressure and SV formation rate. Stress may stimulate an elevated rate of SV formation, which by exposing more adaptive mutations to selection could provide a path for rapid adaptive evolution. Finally, we will determine if the accuracy with which genomic data can be used to predict individuals with the greatest level of resistance to the disease (genomic prediction) can be significantly improved by incorporating information on SVs.By advancing understanding of the role of SVs in adaptive evolution to newly imposed selection pressures, and through developing effective strategies for improving genomic prediction, this project will also enhance our ability to predict which individuals are most likely to survive future threats and help to inform actions to manage natural populations for increased resilience and protect biodiversity.