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

我们缺乏关于(I)自然脊椎动物种群内免疫遗传随时间变化的速率，(Ii)不同的突变过程如何促进它，以及(Iii)特定病原体介导的机制(杂合子优势，频率依赖和波动选择)在这方面的作用的基础知识1，2。在后基因组学时代，已经识别了许多免疫基因3，并且存在使用博物馆样本筛选这些基因的方法7。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。横跨马卡罗尼亚的13个离散岛屿种群使其成为研究野生进化过程的极佳系统，主管人员对该物种的生态和人口统计学有深入的了解1，5-7。病原菌群在这些种群中的差异符合生物地理预期，因此产生了始终如一的不同选择制度。遗传漂移的力量也因不同的有效种群大小而有所不同6学生将使用13个微管基因组--最近作为另一个项目的一部分测序--来量化种群之间的基因组差异，并识别高度差异的免疫位点，这些免疫位点是病原体介导的选择的候选对象。然后，他们将开发序列捕获探针(MyBaits)，在每个时间点从四个最分散的种群中分别筛选25个样本。序列捕获允许以较低的成本对多个个体的大量基因进行测序。重要的是，使用少量降解的DNA(即博物馆样本)可以很好地工作7。学生将使用已有的1820(博物馆)和2006年的样本，但自己收集2020年的样本。他们将开展实现这些目标的所有分子工作和生物信息学工作，包括利用2020年的样本进行病原体筛选，以量化人群中的病原体状况。明确的目标为创作高质量、新颖的作品提供了一个坚实的概念框架，但也为独立开发留出了空间。例如，开发和测试关于病原体介导的选择机制将如何影响时间免疫遗传变异的假设，或跟进工作中产生的额外问题--例如特定病原体可能如何与基因组变异相关。初始基因组已经存在，大多数时间样本和病原体数据也是如此，加上主管在所需的基因组和生物信息学工具方面有相当多的经验，以及在概念领域1、2、5-7、9的专业知识。因此，这是一个以低风险方式研究围绕基本概念的前沿问题的特殊机会。产生的数据将足够强大和集中，足以提供明确的结果，但也足够温和，便于管理。因此，该项目非常适合博士生。UEA主管将提供专业的分子、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能力。野外工作和动物处理技能将由DSR教授。在特内里夫度过的时间将提供一个绝佳的机会来体验不同的学术环境，从而促进个人的全面发展，项目的整体合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.