Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Journal name:
Nature Genetics
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Published online

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.

At a glance


  1. Genomic maximum parsimony tree and divergence dates based on 1,364 non-repetitive, non-homoplastic SNPs from 3,349 coding sequences in 16 Y. pestis genomes (excluding FV-1).
    Figure 1: Genomic maximum parsimony tree and divergence dates based on 1,364 non-repetitive, non-homoplastic SNPs from 3,349 coding sequences in 16 Y. pestis genomes (excluding FV-1).

    Black text, names of genomic sequences (Supplementary Table 1); colored text, branch and population names; gray, ranges of maximal and minimal dates of divergence for individual branches calculated22 with strict mutation rates of 2.9 × 10−9 and 2.3 × 10−8 per site per year (Supplementary Table 2). Comparable results were obtained using intergenic SNPs or a variable clock rate (Supplementary Table 2b). ya, years ago.

  2. Fully parsimonious minimal spanning tree of 933 SNPs for 282 isolates of Y. pestis colored by location.
    Figure 2: Fully parsimonious minimal spanning tree of 933 SNPs for 282 isolates of Y. pestis colored by location.

    Large, bold text, branches 1, 2 and 0; smaller letters, populations (for example, 1.ORI3); lower case letters, nodes (for example, 1.ORI3.a). Strain designations near terminal nodes, genomic sequences. Roman numbers, hypothetical nodes. Gray text on lines between nodes, numbers of SNPs, except that one or two SNPs are indicated by thick and thin black lines, respectively. Six additional isolates in 0.PE1 and 0.PE2b (blue dashes) were tested only for selected, informative SNPs.

Accession codes

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Author information

  1. These authors contributed equally to this work. Present addresses: Max-Planck-Institut für molekulare Genetik, Berlin, Germany (G.M. and B.K.), Berlin Center for Genomics in Biodiversity Research, Berlin, Germany (C.J.M.) and Max-Delbrück-Centrum für molekulare Medizin (MDC) Berlin-Buch, Berlin, Germany (M.F.).

    • Giovanna Morelli,
    • Yajun Song,
    • Camila J Mazzoni &
    • Mark Eppinger


  1. Max-Planck-Institut für Infektionsbiologie, Department of Molecular Biology, Berlin, Germany.

    • Giovanna Morelli,
    • Camila J Mazzoni,
    • Philippe Roumagnac,
    • Mirjam Feldkamp,
    • Barica Kusecek,
    • Thierry Wirth &
    • Mark Achtman
  2. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

    • Yajun Song,
    • Yanjun Li,
    • Yujun Cui &
    • Ruifu Yang
  3. Environmental Research Institute, University College Cork, Cork, Ireland.

    • Yajun Song,
    • Camila J Mazzoni &
    • Mark Achtman
  4. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Mark Eppinger &
    • Jacques Ravel
  5. Centre de Coopération Internationale en Recherche Agronomique pour le Développement, Mixte Research Unit Biology and Genetics of Plant/Pathogen Interactions (UMR BGPI), Montpellier, France.

    • Philippe Roumagnac
  6. Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, USA.

    • David M Wagner,
    • Amy J Vogler &
    • Paul Keim
  7. The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Nicholas R Thomson
  8. Medical Research Council (MRC) Centre for Outbreak Analysis and Modeling, Imperial College Faculty of Medicine, London, UK.

    • Thibaut Jombart &
    • Francois Balloux
  9. Muséum National d′Histoire Naturelle–Ecole Pratique des Hautes Etudes, Department of Systematics and Evolution UMR-CNRS 7205, Paris, France.

    • Raphael Leblois &
    • Thierry Wirth
  10. Institute of Human Genetics, German Research Center for Environmental Health, Neuherberg, Germany.

    • Peter Lichtner
  11. Unité Peste, Institut Pasteur de Madagascar, Madagascar.

    • Lila Rahalison
  12. Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.

    • Jeannine M Petersen
  13. Pathogen Genomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.

    • Paul Keim
  14. Institut Pasteur, Yersinia Research Unit, Paris, France.

    • Elisabeth Carniel
  15. Department of Microbiology, University College Cork, Cork, Ireland.

    • Mark Achtman


M.A., T.W., D.M.W., P.R., J.R., R.Y. and P.K. designed the study. L.R., J.M.P., R.Y. and E.C. contributed Y. pestis DNA and demographic information. G.M., Y.S., M.E., P.R., M.F., B.K., A.J.V., Y.L., Y.C., P.L. and N.R.T. performed sequencing, SNP discovery, MassArray and SNP testing. G.M., Y.S., C.J.M., M.E., P.R., D.M.W. and P.L. performed bioinformatic analyses of the data. C.J.M., T.J., R.L., F.B. and T.W. performed population genetic analyses. M.A., C.J.M., M.E., P.R., D.M.W., T.J., F.B., P.K., T.W., J.R., R.Y. and E.C. wrote the manuscript.

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The authors declare no competing financial interests.

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