Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death
- Verena J. Schuenemanna,1,
- Kirsten Bosb,1,
- Sharon DeWittec,
- Sarah Schmedesd,
- Joslyn Jamiesonb,
- Alissa Mittnika,
- Stephen Forrestb,
- Brian K. Coombese,
- James W. Woodf,g,
- David J. D. Earne,h,
- William Whitei,2,
- Johannes Krausea,j,3, and
- Hendrik N. Poinarb,e,3
- aInstitut für Naturwissenschaftliche Archäologie, University of Tübingen, 72072 Tübingen, Germany;
- bMcMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, ON, Canada L8S 4L8;
- cDepartment of Anthropology, University at Albany, State University of New York, Albany, NY 12222;
- dInstitute of Investigative Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107;
- eMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada L8S 4L8;
- fDepartment of Anthropology, Pennsylvania State University, University Park, PA 16802;
- gPopulation Research Institute, Pennsylvania State University, University Park, PA 16802;
- hDepartment of Mathematics and Statistics, McMaster University, Hamilton, ON, Canada L8S 4L8;
- iCentre for Human Bioarcheology, Museum of London, London EC2Y 5HN, United Kingdom; and
- jHuman Genetics Department, Medical Faculty, University of Tübingen, 72076 Tübingen, Germany
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Edited by Francisco Mauro Salzano, Instituto de Biociencias, Porto Alegre, RS, Brazil, and approved July 22, 2011 (received for review March 30, 2011)
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.
Footnotes
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↵1V.J.S. and K.B. contributed equally to this work.
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↵2Deceased December, 2010.
- 3To whom correspondence may be addressed. E-mail: johannes.krause{at}uni-tuebingen.de or poinarh{at}mcmaster.ca.
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Author contributions: K.B., S.D., B.K.C., J.W.W., D.J.D.E., W.W., J.K., and H.N.P. designed research; V.J.S., K.B., S.D., S.S., J.J., A.M., S.F., J.W.W., and J.K. performed research; B.K.C. and W.W. contributed new reagents/analytic tools; V.J.S., K.B., J.K., and H.N.P. analyzed data; and K.B., J.K., and H.N.P. wrote the paper.
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The authors declare no conflict of interest.
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Data deposition: The sequence reported in this paper has been deposited in the Genbank database (accession nos. HE576978–HE576987).
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See Commentary on page 15669.
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This article is a PNAS Direct Submission.
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See Author Summary on page 15673.
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This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1105107108/-/DCSupplemental.
Freely available online through the PNAS open access option.
