Diversity and evolution of vertebrate immune system genes in the natural environment.

自然环境中脊椎动物免疫系统基因的多样性和进化。

• 批准号: NE/J007307/1
• 负责人: Steve Paterson
• 金额: $ 47.58万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FJ007307%2F1
• 关键词: Diversity; evolution; vertebrate; immune; system

A major part of biodiversity research is to understand the consequences of genetic differences between individuals. Such differences may mean that some individuals are more resistant to infectious diseases than others. Indeed, genes involved in the immune system often exhibit evidence that evolution has driven their genetic diversity. However, such evidence has so far been relatively piecemeal: either studies of a very limited number of genes in the natural environment; or studies of entire genomes, but divorced from any ecological information. Here we propose a more comprehensive approach that exploits (i) the latest sequencing technology to rapidly assay genetic diversity across hundreds of genes, and (ii) detailed ecological datasets relating individual genotype to pathogen resistance and immune phenotype.Our study is based on a pair of wild rodent species, wood mice and field voles, that are common in the UK and are host to a variety of pathogens in the natural environment and which have been characterised for large numbers of samples in previous studies. Thus we have a replicated study in which we will ask: How many genes are under selection and what do these genes do? Does evolution target the same genes in different species? Are genes that are diverse within a species also divergent between species? Do differences between individuals at these genes cause differences in resistance to pathogens?This proposal is fundamental, blue-skies research with broad implications: In conservation, there has been a long-standing interest in conserving genetic biodiversity, particularly to protect populations from epidemics of infectious disease. But it has not been clear what genes are important for such diversity and this proposal will help us understand what to conserve. In biomedicine, much of our understanding of immunology derives from the laboratory mouse, but only in animals with a very limited genetic diversity and with no interaction with the natural environment. Studies of wild rodents, such as we propose, should help to place results from the laboratory mouse into a more ecological context. In so doing, our results may help to inform immunological studies of humans, particularly in the developing world, where there is considerable interest in understanding why some individuals are resistant and some susceptible to common and fatal diseases such as malaria and TB. In evolutionary biology, there is a wealth of theory on the role of pathogens to drive the evolution of hosts and vice versa. But data with which to test the theory, and to drive the field forward, is mostly lacking. We now have the tools to provide such data and to examine the role of pathogens for the evolution of host genomes in the natural environment. The proposed work may highlight novel genes that are highly diverse, or evolving rapidly, that will provide exciting avenues of future research.

生物多样性研究的一个主要部分是了解个体之间遗传差异的后果。这种差异可能意味着一些人比其他人更能抵抗传染病。事实上，参与免疫系统的基因经常表现出进化驱动其遗传多样性的证据。然而，到目前为止，这些证据相对零散：要么是对自然环境中数量非常有限的基因的研究;要么是对整个基因组的研究，但与任何生态信息无关。在这里，我们提出了一个更全面的方法，利用（i）最新的测序技术，快速测定数百个基因的遗传多样性，（ii）详细的生态数据集，将个体基因型与病原体抗性和免疫表型联系起来。我们的研究是基于一对野生啮齿动物物种，木鼠和田鼠，在英国很常见，在自然环境中是各种病原体的宿主，在以前的研究中已经对大量样本进行了表征。因此，我们有一个重复的研究，我们会问：有多少基因在选择中，这些基因做什么？进化是否针对不同物种中的相同基因？同一物种内的基因多样性在不同物种间也是多样的吗？个体之间在这些基因上的差异是否会导致对病原体抵抗力的差异？这一建议是具有广泛影响的基础性、蓝天研究：在保护方面，人们长期以来一直对保护遗传生物多样性感兴趣，特别是保护人口免受传染病流行的影响。但目前还不清楚哪些基因对这种多样性很重要，这项提议将帮助我们了解应该保护哪些基因。 在生物医学中，我们对免疫学的大部分理解来自实验室小鼠，但仅限于遗传多样性非常有限且与自然环境没有相互作用的动物。正如我们所建议的，对野生啮齿动物的研究应该有助于将实验室小鼠的结果置于更生态的背景下。在这样做的过程中，我们的结果可能有助于为人类的免疫学研究提供信息，特别是在发展中国家，人们对理解为什么有些人对疟疾和结核病等常见和致命疾病具有抵抗力而有些人则易感有相当大的兴趣。在进化生物学中，有大量关于病原体驱动宿主进化的理论，反之亦然。但是，用来检验这一理论并推动这一领域向前发展的数据大多缺乏。我们现在有工具来提供这些数据，并研究病原体在自然环境中宿主基因组进化中的作用。拟议的工作可能会突出高度多样化或快速进化的新基因，这将为未来的研究提供令人兴奋的途径。

项目成果

Host-parasite biology in the real world: the field voles of Kielder.

• DOI: 10.1017/s0031182014000171
• 发表时间: 2014-07
• 期刊: Parasitology
• 影响因子: 2.4
• 作者: Turner AK;Beldomenico PM;Bown K;Burthe SJ;Jackson JA;Lambin X;Begon M
• 通讯作者: Begon M

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis).

在田鼠（Microtus agrestis）自然群体中鉴定出的候选耐受基因。

• DOI: 10.1111/mec.14476
• 发表时间: 2018
• 期刊: Molecular ecology
• 影响因子: 4.9
• 作者: Wanelik KM