Uncovering the genomic history of the second plague pandemic through analysis of historical Yersinia pestis genomes

Yersinia pestis, the causative agent of plague, has affected humans in Eurasia since 5,000 years ago and was the main culprit of two historically recorded pandemics that caused immense populating declines between the 6th century AD and the Early Modern Era. The present study focuses on the second plague pandemic, which began with the Black Death (1346-1353 AD) and persisted with repeated epidemics in Europe until the 18th century AD. Here, we report over 30 ancient Y. pestis genomes spanning the 14th to 17th century AD through the analysis of human remains from epidemics cemeteries across the continent. Our data support historical sources suggesting an initial entry of the bacterium from Eastern Europe. In addition, we show an absence of genetic diversity in the bacterium during the Black Death as well as low diversity during local outbreaks thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. Finally, through integration of the newly generated genomes with available modern and ancient Y. pestis datasets, we show the loss of a genomic region that includes virulence-associated genes in strains associated with late stages of the second plague pandemic (17th - 18th century AD). This deletion could not be detected in extant strains within our modern dataset, though it was identified among the most derived isolates of a today-extinct lineage associated with the first plague pandemic (6th - 8th century AD), potentiating a case of convergent evolution between both pandemic events within Europe