基于古DNA技术的中国古代疫病致病菌的基因组学和进化历史研究

获取并分析中国古代重大疫情爆发中致病菌基因组可以揭示破坏性历史灾难背后的动因，追踪史前时期致病菌的地理传播以及进化模式，对于考古学和微生物学研究意义重大。目前国内还没有相关研究的报道。本研究组通过筛查本实验室的中国新石器至铁器时代古代个体的Shotgun数据，发现四处遗址的个体牙髓腔宏基因组中含有致病菌阳性信号，并进一步获取了新疆泉儿沟遗址发现的肠炎沙门氏菌杆菌完整的基因组信息，建立了完善的古致病菌研究流程。本研究拟针对在古代样本中发现的鼠疫耶尔森氏菌和结核杆菌设计合成目标捕获探针，结合高通量测序平台进行致病菌基因组重建, 通过分析与欧亚大陆其他地区发现的古代致病菌的系统发育关系，来推测致病菌的传播模式和传播历史；并研究导致细菌生境适应、毒力进化、耐药性产生等表型进化的遗传基础。本研究可以帮助了解中国疫病史以及致病菌进化历史，同时为传染病的防治提供重要的理论基础。

Obtaining and analyzing the genomes of pathogens in major outbreaks of ancient China can reveal the motivation behind the devastating historical catastrophe and trace the geographical dissemination and evolutionary patterns of pathogens in prehistoric times, which are of great significance to archaeological and microbiological research. So far, there has been no report on retrieving the ancient pathogen genome successfully in China. Four archaeological sites were identified as study targets through screening whole-genome data of ancient individuals which were collected from the Bronze Age to Iron Age in our laboratory. In this study, the target capture probes were designed and synthesized based on the bacterial strains found, and then combined with high-throughput sequencing platform for deep sequencing; Meanwhile，the calculation method for automatic pathogen screening and candidate sequence certification was used to reconstruct the genomes of pathogenic bacteria.The patterns of dissemination of pathogens were speculated by analyzing the phylogenetic relationships with ancient pathogens found in other parts of Eurasia. We will study the genetic basis that led to phenotypic evolution such as bacterial adaptation, virulence evolution and drug resistance. This study can help to understand the history of human diseases and the evolutionary history of pathogens, and provide an important theoretical basis for the prevention and treatment of infectious diseases.