Pathogens past and present - reconstructing historical and ancient host jumps

在过去的几十年里，被称为“古代DNA测序”的技术的快速发展优化了对尸体、博物馆和考古标本的DNA测序，为在其进化史的特定时间点恢复大量物种的基因组提供了前所未有的机会。鉴定古代DNA中的微生物基因组可以确定病原体何时开始在一个物种中传播，推断过去的传播以及鉴定宿主适应和传染性的基因组决定因素。这些观察结果可以与当代临床和兽医感染数据相结合，形成一个分析框架，揭示当今宿主-微生物关联的途径。这个博士项目将利用结合古代和现代微生物基因组数据的独特潜力来解决主要问题，包括：i)微生物在人类和其他动物之间的传播是如何在历史上保持或改变的？ii)与人类和动物相关的主要微生物的传播方向是什么？iii)在感染特定宿主的病原体中富集了哪些基因组特征？它们是何时进化的？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，包括人类和猪的主要人畜共患病(例如。沙门氏菌。丹毒杆菌（Erysipelothrix, Yersinia）和其他相关的驯化物种，从新石器时代一直到现在。利用在轮转项目中最初学到的技能，将应用包括宏基因组分类、群体遗传学和系统发育尖端年代测定在内的分析。利用泛基因组重建方法，与宿主变化相关的蛋白质将被确定为假定的适应机制，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进行背景化。综上所述，该博士将利用古代基因组学的扩展工具包，从一个新的历史角度来解决人畜共患疾病的当代挑战。

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.