Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid ofYersinia pestisfrom victims of the Black Death

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Abstract
Although investigations of medieval plague victims have identifiedYersinia pestisas the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348–1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human andY. pestisDNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modernY. pestisshows identity with several isolates matching theMedievalisbiovar; however, our chromosomal sequences indicate the victims were infected with aY. pestisvariant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant ofY. pestisthat may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms ofY. pestisinfections.