Evolution in action: using museum DNA to understand disease resistance in island birds

我们缺乏以下方面的基本知识：(1)自然脊椎动物种群中免疫遗传随时间变化的速率，(2)不同的突变过程如何促进免疫遗传变化，以及(3)特定病原体介导的机制（杂合子优势、频率依赖和波动选择）在这一过程中的作用1,2。在后基因组学时代，许多免疫基因已经被鉴定出来，并且存在着利用博物馆样本筛选这些基因座的方法。因此，如果有足够的时间样本，现在就有可能研究野生种群的时间免疫遗传变化。在马卡罗尼西亚分布着13个分散的贝特洛特皮皮岛种群，这使它成为研究野外进化过程的一个极好的系统，管理人员对这个物种的生态学和人口学有深入的了解。根据生物地理预期，这些种群中的病原体区系各不相同，从而产生了一贯不同的选择机制。遗传漂变的力量也因有效种群规模的不同而不同。该学生将使用13个pipit基因组（最近作为另一个项目的一部分进行了测序）来量化种群之间的基因组差异，并确定高度分化的免疫位点，这些位点是病原体介导选择的候选位点。然后，他们将开发序列捕获探针（myBaits），在每个时间点从四个最不同的种群中筛选出25个样本。序列捕获允许以低成本对多个个体的大量基因进行测序。重要的是，它可以很好地使用少量降解的DNA（即博物馆样本）。学生将使用已有的1820年（博物馆）和2006年的样本，但自己收集2020年的样本。他们将承担所有的分子工作和生物信息学工作，以实现这些目标，包括病原体筛选，利用2020年的样本对人群中的病原体状况进行量化。明确的目标提供了一个坚实的概念框架，以产生高质量，新颖的工作，但允许独立开发的范围。例如，发展和测试关于病原体介导的选择机制如何影响时间免疫遗传变异的假设，或者跟进这项工作产生的其他问题——例如特定病原体如何与基因组变异相关联。最初的基因组已经存在，大多数时间样本和病原体数据也已经存在，加上导师在所需的基因组和生物信息学工具方面具有丰富的经验，并且在概念领域具有专业知识1,2,5-7,9。因此，这是一个极好的机会，以低风险的方式研究围绕一个基本概念的前沿问题。生成的数据将足够强大和集中，足以提供明确的结果，但又足够适度，便于管理。因此，这个项目非常适合博士研究生。东英吉利大学的导师将提供专家分子、生物信息学和数据分析培训。所有导师将帮助培养学生的概念理解和科学沟通技巧。现场工作和动物处理技能将由DSR教授。在特内里费岛度过的时间将提供一个极好的机会，体验不同的学术环境，从而促进个人的全面发展。项目的整体协作性质将促进团队合作，沟通和网络。

We lack fundamental knowledge of (i) the rate of immunogenetic change over time within natural vertebrate populations, (ii) how different mutational processes facilitate it, and (iii) the role of specific pathogen-mediated mechanisms (heterozygote advantage, frequency-dependent and fluctuating selection) in this1,2. In the post-genomics era numerous immune genes have been identified3 and methods exist to screen such loci using museum samples7. Consequently, it is now possible to investigate temporal immunogenetic change in wild populations if sufficient temporal samples are available4. The 13 discrete island populations of Berthelot's pipit across Macaronesia make it an excellent system for studying evolutionary processes in the wild, and the supervisors have in-depth understanding of this species' ecology and demography1,5-7. Pathogen faunas differ across these populations in line with biogeographical expectations5 thus generating consistently differing selection regimes. The force of genetic drift also differs because of contrasting effective population sizes6.The student will use 13 pipit genomes - recently sequenced as part of another project - to quantify genomic divergence between populations and identify highly divergent immune loci that are candidates for being under pathogen-mediated selection. They will then develop sequence capture probes (myBaits) to screen 25 samples from each of the four most divergent populations at each time point. Sequence capture allows for the sequencing of large numbers of genes across multiple individuals at low cost8. Importantly, it works well using small amounts of degraded DNA (i.e. museum samples)7. The student will use the 1820 (museum) and 2006 samples already available, but collect the 2020 samples themselves. They will undertake all the molecular work and bioinformatics work to address the objectives, including pathogen screening to quantify pathogen regimes across populations5 using the 2020 samples. The defined objectives provide a firm conceptual framework to produce high quality, novel work, but allow scope for independent development. For example, developing and testing hypotheses on how pathogen-mediated selection mechanisms will affect temporal immunogenetic variation, or following up additional questions arising from the work - such as how specific pathogens may be associated with genomic variation.The initial genomes already exist, as do the majority of temporal samples and pathogen data, plus the supervisors have considerable experience with the required genomic and bioinformatics tools, and expertise in the conceptual area1,2,5-7,9. This is therefore an exceptional opportunity to investigate cutting-edge questions around a fundamental concept in a low-risk manner. The data generated will be sufficiently powerful and focused enough to provide clear results, but modest enough to be manageable. Thus the project is ideally suited to a PhD studentship.The UEA supervisors will provide expert molecular, bioinformatics and data analysis training. All supervisors will help develop the student's conceptual understanding and scientific communication skills. Fieldwork and animal handling skills will be taught by DSR. The time spent in Tenerife will provide an excellent opportunity to experiencing a different academic environment thus promoting overall personal development, The overall collaborative nature of the project will facilitate teamwork, communication and networking.