鼠疫是严重危害人类健康的烈性传染病，历史上曾有三次大流行；基于群体遗传学和考古微生物学的研究已将导致三次大流行的鼠疫菌株进行了系统发育定位。本项目将选择分离自我国12个鼠疫疫源地的2000株代表性菌株，基于前期确定的鼠疫菌精细群体遗传结构，筛选关键SNP位点进行菌株分型和系统发育分析，确定菌株的种群位置。随后选择关键种群的中国菌株进行全基因组序列测定，进一步了解鼠疫菌物种发生早期时的遗传事件，并厘清中国菌株与黑死病（第二次大流行）菌株、查士丁尼（第一次大流行）菌株之间的遗传关系。同时对所有菌株进行MLVA分析和CRISPR分析，深入解析中国鼠疫菌株基因组多态性及其微进化过程，以谱系生物地理学的研究思路，重建鼠疫菌在中国境内扩散及向境外扩散的精细路线图。最后将所有数据加以整合，建立我国鼠疫菌代表性菌株的基因组多态性数据库，为特定种群菌株的快速检测、菌株溯源以及鼠疫疫情扩至等工作提供科学依据。

Plague, caused by Yersinia pestis, is a notorious infectious disease, which had claimed millions of lives during the three major plague pandemics (the first pandemic: Justinian Plague, the second pandemic: Black Death, the third pandemic: Modern Plague) in the human history. Based on the population genetics and palaeomicrobiological analysis, the causative isolates of the historical plague pandemics had been mapped to the phylogenic tree of Y. pestis. In this study, we will select 2000 representative strains isolated from all 12 plague foci in China. Then we will choose the key informative SNPs based on the predefined fine population structure framework of Y. pestis, and mapped all the isolates into the corresponding populations according to the SNP genotyping and phylogenic analysis. By deciphering the genomes of specific strains from important populations (such as the most ancient populations, populations related to Justinian plague isolates and Black Death isolates), we will be able to understand the evolution events during the origination and speciation of Y. pestis, and clarify the genetic relationships between Chinese isolates and the historical pandemic strains as well. Meanwhile, we will perform extensive MLVA and CRIPSR genotyping, aiming to portrait the genomic polymorphisms and evolutionary scenarios of all the Chinese isolates in details, which will be of great help in reconstructing the dissemination routes of Y. pestis inside and outside of China. More importantly, we will integrate all the polymorphism data and isolates information to develop a genomic polymorphisms database for Y. pestis, which will serve as a fundamental tool for strain source-tracing in plague outbreaks or bioterrorism attacks.