The role of epigenetics in evolution

表观遗传学在进化中的作用

• 批准号: NE/V010921/1
• 负责人: J Slate
• 金额: $ 166.36万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FV010921%2F1
• 关键词: role; epigenetics; evolution

Every young biologist learns about DNA, the genetic code and how mutations in that code lead to variation. However, it is less well known that a gene's activity or function can be modified without any change in the genetic sequence; this type of modification is known as epigenetics. Epigenetics has become an important and timely topic across most fields of biological research including medicine, animal and plant breeding, developmental biology and the discipline I work in, evolutionary genetics.The commonest form of epigenetic effect is known as methylation, which most frequently arises when a methyl group (-CH3) replaces a hydrogen ion on the pyrimidine ring of the nucleotide cytosine (the DNA 'letter' C). Methylation can happen at C bases all over the genome, and it is thought to have the potential to effect how particular genes are expressed and regulated i.e. it could determine which tissues a gene is 'turned on in' and when it is turned on. It is becoming increasingly apparent that there is a great deal of variation in methlyation e.g. between individuals, between different tissues in the same individual and at different times in an individual's lifetime. However, we know very little about whether this variation in methylation has consequences for how phenotypes are expressed, how it is inherited, and whether it can play an important role in evolutionary change.This project seeks to understand the role of epigenetics on evolutionary change in two discrete but complementary work packages. The work will be done in a population of Soay sheep on the island of Hirta, St Kilda in the Outer Hebrides. This population is one of the best studied mammal populations in the world. It has many features that make it ideal to explore the role of epigenetics on evolution. Complete life histories are known for around 10,000 sheep born since 1985. Environmental conditions on the island are challenging, meaning natural selection is strong enough for evolutionary change to have been witnessed and measured in the lifetime of the study. Extensive genomics resources are already available, along with freezers full of archived material. Both work packages will be underpinned by an initial goal of sequencing 1000 entire methylomes (the methylation equivelent of a genome) Work Package 1 will explore whether epigenetic variation explains substantial amounts of phenotypic variation. If it does, is that variation heritable? And if it is heritable, is that variation responsible for the so-called 'missing heritability', where conventional (DNA-sequence based) genome scans fail to identify all of the genetic variants affecting a trait? Work Package 2 will test ideas that methylation is sensitive to environmental conditions and can reveal new insights into previous life experiences, body condition, and future longevity. WP1 will resolve topical and controversial questions about the relative importance of genetics and epigenetics on phenotypic variation and evolutionary change. WP2 will result in the first application of epigenetic clocks to study health and ageing in any wild animal population. Together, the outcomes will give unprecedented insight into the environmental and genetic causes of variation in methylation and what that variation means for individual fitness and a population's ability to respond and adapt to environmental change.

每一个年轻的生物学家都学习DNA，遗传密码以及密码中的突变如何导致变异。然而，不太为人所知的是，基因的活性或功能可以在不改变遗传序列的情况下被修饰;这种类型的修饰被称为表观遗传学。表观遗传学已经成为生物学研究领域的一个重要而及时的话题，包括医学、动植物育种、发育生物学和我所从事的进化遗传学。表观遗传效应最常见的形式是甲基化，最常见的是当甲基（-CH 3）取代核苷酸胞嘧啶（DNA "字母" C）的嘧啶环上的氢离子时。甲基化可以发生在整个基因组的C碱基上，并且它被认为有可能影响特定基因的表达和调节，即它可以决定基因在哪些组织中被"打开"以及何时被打开。越来越明显的是，甲基化存在大量变异，例如个体之间，在同一个体的不同组织之间以及在个体一生中的不同时间。然而，我们知道很少这种甲基化的变化是否有后果表型如何表达，它是如何遗传的，以及它是否可以在进化中发挥重要作用。这个项目旨在了解表观遗传学的作用，在两个独立的，但互补的工作包的进化变化。这项工作将在外赫布里底群岛圣基尔达赫塔岛的Soay羊群中进行。这个种群是世界上研究得最好的哺乳动物种群之一。它具有许多特点，使其成为探索表观遗传学在进化中的作用的理想选择。自1985年以来，已知约有10，000只绵羊出生。岛上的环境条件具有挑战性，这意味着自然选择足够强大，足以在研究期间目睹和测量进化变化。广泛的基因组学资源已经可用，沿着的还有装满存档材料的冰柜。这两个工作包将以测序1000个完整甲基化组（相当于基因组的甲基化）的初始目标为基础。工作包1将探索表观遗传变异是否能解释大量的表型变异。如果是这样，这种变异是可遗传的吗？如果它是可遗传的，那么这种变异是否就是所谓的“缺失遗传性”的原因，即传统的（基于DNA序列的）基因组扫描无法识别影响一个性状的所有遗传变异？工作包2将测试甲基化对环境条件敏感的想法，并可以揭示对以前生活经历，身体状况和未来寿命的新见解。WP1将解决关于遗传学和表观遗传学对表型变异和进化变化的相对重要性的热门和有争议的问题。WP2将导致表观遗传时钟首次应用于研究任何野生动物种群的健康和衰老。总之，这些结果将为甲基化变异的环境和遗传原因以及这种变异对个体适应性和种群响应和适应环境变化的能力意味着什么提供前所未有的见解。