Genetic Evidence of Yersinia pestis from the First Pandemic.

Background/Objectives: The Plague of Justinian marked the beginning of the First Pandemic (541-750 CE), yet no genomic evidence of Yersinia pestis has previously been recovered from the Eastern Mediterranean, where the outbreak was first recorded. This study aimed to determine whether Y. pestis was present in a mid-6th to early 7th century mass grave in Jerash, Jordan, and to characterize its genome within the broader context of First Pandemic strains. Methods: We analyzed samples from multiple individuals recovered from the Jerash mass grave. Initial screening for potential pathogen presence was conducted using proteomics. Select samples were subjected to ancient DNA extraction and whole genome sequencing. Comparative genomic and phylogenetic analyses were conducted to assess strain identity and evolutionary placement. Results: Genomic sequencing recovered Y. pestis DNA from five individuals, revealing highly similar genomes. All strains clustered tightly with other First Pandemic lineages but were notably recovered from a region geographically close to the pandemic's historical epicenter for the first time. The near-identical genomes across diverse individuals suggest an outbreak of a single circulating lineage at the time of this outbreak. Conclusions: This study provides the first genomic evidence of Y. pestis in the Eastern Mediterranean during the First Pandemic, linking archaeological findings with pathogen genomics near the origin point of the Plague of Justinian. Summary Sentence: Genomic evidence links Y. pestis to the First Pandemic in an ancient city.