Pathogens past and present - reconstructing historical and ancient host jumps

在过去的几十年里，被优化为对身体、博物馆和考古标本的DNA进行测序的技术的快速发展，被称为“古代DNA测序”，为在物种进化史上的特定时间点恢复物种的正常基因组提供了前所未有的机会。对古代DNA中微生物基因组的识别可以准确地确定病原体何时开始在物种中传播，推断过去的传播，并识别宿主适应和传染性的基因组决定因素。这种观察可以与当代临床和兽医感染数据相结合，在一个分析框架中揭示当今宿主-微生物联系的途径。这个博士项目将利用古代和现代微生物基因组数据相结合的独特潜力来解决主要问题，包括：i)历史上微生物在人类和其他动物之间的传播是如何维持或改变的？二)与人和动物有关的主要微生物的传播方向是什么？Iii)感染特定宿主的病原体丰富了哪些基因组特征，它们是什么时候进化的？在博士期间，学生将筛选从一系列历史和考古材料中获得的已发表和新生成的数据，包括人和猪的关键人畜共患病(例如。沙门氏菌。Erysipelothrix，Yersinia)和其他相关的家养动物从新石器时代一直到现在。利用在轮换项目中最初学到的技能，将进行分析，包括元基因组分类、种群遗传学和系统发育尖端年代测定。利用泛基因组重建方法，与宿主变化相关的蛋白质将被识别为假定的适应机制，包括对它们何时进化的估计。结果将通过与考古学家、流行病学家和微生物学家的合作来确定。综上所述，这位博士将利用古代基因组学的扩展工具包，从一个新颖的历史角度来应对人畜共患病的当代挑战。

Over the past decades, the rapid development of techniques optimised to sequencethe DNA of post-mortem, museum, and archaeological specimens, termed 'ancientDNA sequencing', has provided unprecedented opportunities to recover genomes of amultitude of species at specific points in their evolutionary history. Identification of thegenomes of microbes within ancient DNA can pinpoint when a pathogen first started tocirculate in a species, inference of past transmissions and identification of genomicdeterminants of host-adaptation and infectivity. Such observations can be combinedwith contemporary clinical and veterinary infection data in an analytical frameworkthat unveils the path to host-microbe associations today. This PhD project will harnessthe unique potential of combining ancient and modern microbial genomic data toaddress major questions including: i) How has the spread of microbes betweenhumans and other animals been maintained or changed over history? ii) What is thedirection of transmission of major microbes associated to humans and animals? iii)What genomic features are enriched in pathogens infecting specific hosts and whendid they evolve? During the PhD, the student will screen published and newlygenerated data obtained from a range of historic and archaeological material toinclude key zoonoses of humans and swine (eg. Salmonella. Erysipelothrix, Yersinia)and other relevant domesticates spanning the Neolithic through to present. Using skillsinitially learned during the rotation project, analyses will be applied includingmetagenomic classification, population genetics and phylogenetic tip-dating. Usingpan-genome reconstruction methods, proteins correlated with changing hosts will beidentified as putative adaptive mechanisms including estimation of when they evolved.Results will be contextualised via collaboration with archaeologists, epidemiologists,and microbiologists. Taken together, this PhD will take advantage of the expandingtoolkit of ancient genomics to address the contemporary challenge of zoonotic diseasefrom a novel historic perspective.