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Keller, Marcel; Spyrou, Maria A.; Scheib, Christiana L.; Neumann, Gunnar U.; Kropelin, Andreas; Haas-Gebhard, Brigitte; Paffgen, Bernd; Haberstroh, Jochen; Ribera i Lacomba, Albert; Raynaud, Claude; Cessford, Craig; Durand, Raphael; Stadler, Peter; Nagele, Kathrin; Bates, Jessica S.; Trautmann, Bernd; Inskip, Sarah A.; Peters, Joris; Robb, John E.; Kivisild, Toomas; Castex, Dominique; McCormick, Michael; Bos, Kirsten I.; Harbeck, Michaela; Herbig, Alexander and Krause, Johannes (2019): Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750). In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 25: pp. 12363-12372

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The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleo-genomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium's spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymor-phisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

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