The role of structural variants in rapid adaptation

野生物种面临着来自一系列不同威胁的日益增长的压力。其中包括气候变化导致的气温升高以及全球贸易和旅行带来的新的虫害和疾病。世界各地的许多树木目前都面临着这样的威胁，导致它们变得紧张，使它们更难发挥我们所有人都受益的功能，比如捕获和储存二氧化碳，或者通过减少地表水径流来降低洪水风险。最终，无法应对这些威胁的个体将衰落并死亡，这不仅会使整个树木物种处于危险之中，而且还会危及依赖这些物种的相关生物多样性。然而，尽管树种体型庞大，通常寿命很长，但我们知道，树种有潜力迅速适应环境中的新挑战。个体DNA之间的巨大差异，即结构变异，对于快速适应可能特别重要，因为它们可以导致比DNA微小变化更显著的表型变化。直到最近，还不可能在种群水平上正确评估SVS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。这个项目将考察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，我们将使用白蜡树枯萎病(ADB)在英国本土欧洲白蜡树种群中的案例，这为分析对新施加的压力源的进化反应所涉及的基因组变化提供了一个特殊的机会。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，它受到了引起ADB的入侵真菌的严重破坏。虽然大多数灰烬一旦感染这种疾病最终就会死亡，但也有一小部分人具有抵抗力，即使在被患病和垂死的树木包围时仍保持健康。我们将对多个天然的英国白蜡树种群进行采样，其中既有早于亚行疫情的健康和患病的成虫，也有自疾病到来后建立的健康和患病的幼树。我们将对每个种群中的数百个个体进行全基因组测序，并根据他们对疾病的抵抗力水平对他们进行评分。利用这些数据，我们首先将检验SVS与ADB耐药性之间的关联，以与单核苷酸变体(SNPs)相比，估计SVS对耐药性的相对贡献。对于与抗药性显著相关的SVS或SNPs，我们将测试每个种群中世代之间的等位基因频率变化，并分析这是否与年轻队列中对ADB的抵抗力增加有关--这是该物种开始适应疾病的迹象。这将使我们能够确定SVS对正在进行的适应的相对重要性。然后我们将研究疾病压力和SV形成率之间的关系。压力可能会刺激更高的SV形成率，通过将更多的适应性突变暴露在选择中，可以为快速适应性进化提供一条途径。最后，我们将确定基因组数据用于预测对疾病抵抗力最强的个体的准确性(基因组预测)是否可以通过纳入关于SVS的信息而显著提高。通过将对SVS在适应进化中的作用的理解推进到新施加的选择压力，并通过开发有效的策略来改进基因组预测，该项目还将增强我们预测哪些个体最有可能在未来的威胁中幸存下来的能力，并帮助为管理自然种群以提高韧性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.