Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death

Verena J. Schuenemann, Kirsten Bos, Sharon DeWitte, Sarah Schmedes, Joslyn Jamieson, Alissa Mittnik, Stephen Forrest, Brian K. Coombes, James W. Wood, David J.D. Earn, William White, Johannes Krause, Hendrik N. Poinar

Research output: Contribution to journalArticle

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Abstract

Although investigations of medieval plague victims have identified Yersinia pestis as 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 and Y. pestis DNA 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 modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that 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 of Y. pestis infections.

Original languageEnglish (US)
Pages (from-to)E746-E752
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number38
DOIs
StatePublished - Oct 20 2011

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Yersinia pestis
Plague
Plasmids
Virulence
Yersinia Infections
Burial
High-Throughput Nucleotide Sequencing
Mitochondrial Genome
DNA
Pandemics
Human Genome
England

All Science Journal Classification (ASJC) codes

  • General

Cite this

Schuenemann, Verena J. ; Bos, Kirsten ; DeWitte, Sharon ; Schmedes, Sarah ; Jamieson, Joslyn ; Mittnik, Alissa ; Forrest, Stephen ; Coombes, Brian K. ; Wood, James W. ; Earn, David J.D. ; White, William ; Krause, Johannes ; Poinar, Hendrik N. / Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 38. pp. E746-E752.
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Schuenemann, VJ, Bos, K, DeWitte, S, Schmedes, S, Jamieson, J, Mittnik, A, Forrest, S, Coombes, BK, Wood, JW, Earn, DJD, White, W, Krause, J & Poinar, HN 2011, 'Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 38, pp. E746-E752. https://doi.org/10.1073/pnas.1105107108

Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. / Schuenemann, Verena J.; Bos, Kirsten; DeWitte, Sharon; Schmedes, Sarah; Jamieson, Joslyn; Mittnik, Alissa; Forrest, Stephen; Coombes, Brian K.; Wood, James W.; Earn, David J.D.; White, William; Krause, Johannes; Poinar, Hendrik N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 38, 20.10.2011, p. E746-E752.

Research output: Contribution to journalArticle

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N2 - Although investigations of medieval plague victims have identified Yersinia pestis as 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 and Y. pestis DNA 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 modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that 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 of Y. pestis infections.

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