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Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

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  • 10 February 2015

    In the version of this article initially published online, affiliation 3 was incomplete, and the middle initials of author Michael Blum were inadvertently omitted. These errors have been corrected for the print, PDF and HTML versions of this article.


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We gratefully acknowledge L. Cowan and J. Posey (US Centers for Disease Control and Prevention) for providing us with significant amounts of genotyping data for M. tuberculosis Beijing isolates. We thank T. Ubben, I. Radzio, T. Struwe-Sonnenschein and J. Zallet (Research Center Borstel) for excellent technical assistance. We acknowledge J. Peh for her assistance and support in the study and I. Comas for statistical advice. Parts of this work have been supported by grants from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 278864 in the framework of the European Union PathoNGenTrace project and grant agreement 223681 in the framework of the TB-PAN-NET project. We also thank Action Transversale du Muséum National d'Histoire Naturelle 'Les Microorganismes, Acteurs Clés dans les Ecosystèmes' for financial support. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Author notes

    • Philip Supply
    • , Stefan Niemann
    •  & Thierry Wirth

    These authors contributed equally to this work.


  1. Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.

    • Matthias Merker
    • , Thomas A Kohl
    •  & Stefan Niemann
  2. Laboratoire Biologie Intégrative des Population, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, Paris, France.

    • Camille Blin
    • , Stefano Mona
    •  & Thierry Wirth
  3. Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d'Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France.

    • Camille Blin
    • , Stefano Mona
    •  & Thierry Wirth
  4. Université Joseph Fourier, Centre National de la Recherche Scientifique, Laboratoire Techniques de l'Ingénierie Médicale et de la Complexité–Informatique, Mathématiques et Applications, Grenoble, France.

    • Nicolas Duforet-Frebourg
    •  & Michael G B Blum
  5. INSERM U1019, Center for Infection and Immunity of Lille, Lille, France.

    • Sophie Lecher
    • , Eve Willery
    •  & Philip Supply
  6. Centre National de la Recherche Scientifique, UMR 8204, Lille, France.

    • Sophie Lecher
    • , Eve Willery
    •  & Philip Supply
  7. Université Lille Nord, Center for Infection and Immunity of Lille, Lille, France.

    • Sophie Lecher
    • , Eve Willery
    •  & Philip Supply
  8. Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.

    • Sophie Lecher
    • , Eve Willery
    •  & Philip Supply
  9. National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.

    • Sabine Rüsch-Gerdes
  10. Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, St. Petersburg, Russia.

    • Igor Mokrousov
  11. Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.

    • Eman Aleksic
    •  & Suzanne Crowe
  12. Genoscreen, Lille, France.

    • Caroline Allix-Béguec
    • , Céline Wahl
    •  & Philip Supply
  13. Medical Department, Médecins sans Frontières Switzerland, Geneva, Switzerland.

    • Annick Antierens
  14. Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.

    • Ewa Augustynowicz-Kopeć
  15. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

    • Marie Ballif
  16. Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit–Tuberculosis, Universidad Peruana Cayetano Heredia, Lima, Peru.

    • Francesca Barletta
  17. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

    • Hans Peter Beck
    •  & Sébastien Gagneux
  18. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.

    • Clifton E Barry III
    •  & Isdore Chola Shamputa
  19. Clinical Research Department, Epicentre, Paris, France.

    • Maryline Bonnet
    •  & Elisabeth Sanchez-Padilla
  20. Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy.

    • Emanuele Borroni
    •  & Daniela Cirillo
  21. Department of Microbiology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.

    • Isolina Campos-Herrero
  22. Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.

    • Helen Cox
  23. Department of Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia.

    • Suzanne Crowe
  24. Central Clinical School, Monash University, Melbourne, Victoria, Australia.

    • Suzanne Crowe
  25. National Tuberculosis Reference Laboratory, Phthysiopneumology Institute, Chisinau, Republic of Moldova.

    • Valeriu Crudu
  26. Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Germany.

    • Roland Diel
  27. Public Health England National Mycobacterial Reference Laboratory and Clinical Tuberculosis and Human Immunodeficiency Virus Group, Queen Mary's School of Medicine and Dentistry, London, UK.

    • Francis Drobniewski
    •  & Vladyslav Nikolayevskyy
  28. Department of Infectious Diseases, Imperial College, London, UK.

    • Francis Drobniewski
    •  & Vladyslav Nikolayevskyy
  29. Tuberculosis and Mycobacteria, Scientific Institute of Public Health, Brussels, Belgium.

    • Maryse Fauville-Dufaux
  30. Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.

    • Solomon Ghebremichael
  31. Department of Science and Technology/National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research/Medical Research Council, Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

    • Madeleine Hanekom
    •  & Robin Warren
  32. Department of Diagnostics and Vaccinology, Swedish Institute for Communicable Disease Control, Solna, Sweden.

    • Sven Hoffner
  33. Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.

    • Wei-wei Jiao
    •  & Adong Shen
  34. US Agency for International Development Quality Health Care Project, Bishkek, Kyrgyzstan.

    • Stobdan Kalon
  35. Samara Oblast Tuberculosis Service, Samara, Russia.

    • Irina Kontsevaya
  36. Statens Serum Institute, International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark.

    • Troels Lillebæk
    •  & Michael Rasmussen
  37. Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.

    • Shinji Maeda
  38. World Health Organization Supranational Tuberculosis Reference Laboratory, Institut Pasteur de la Guadeloupe, Abymes, France.

    • Nalin Rastogi
  39. Instituto de Investigación Sanitaria Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain.

    • Sofia Samper
  40. Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

    • Branislava Savic
    •  & Dragana Vukovic
  41. Central Tuberculosis Laboratory, Department of Pathology, Singapore General Hospital, Singapore.

    • Li-Hwei Sng
  42. Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.

    • Petras Stakenas
  43. Tartu University Hospital United Laboratories, Mycobacteriology, Tartu, Estonia.

    • Kadri Toit
  44. Medical Department, Médecins sans Frontières, Paris, France.

    • Francis Varaine
  45. German Center for Infection Research, Borstel Site, Borstel, Germany.

    • Stefan Niemann


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I.M., P. Supply, S.N. and T.W. designed the study. M.M., P. Supply, S.N. and T.W. analyzed data and wrote the manuscript with comments from all authors. M.M., C.B., S. Mona and T.W. performed population genetics and phylogenetic analyses. M.M., N.D.-F., M.G.B.B. and T.W. conducted selection tests. T.A.K. performed whole-genome sequencing and SNP calling. P. Supply, M.M., E.W., S.L., S.R.-G., I.M., S.N., E.A., C.A.-B., A.A., E.A.-K., M. Ballif, F.B., H.P.B., C.E.B., M. Bonnet, E.B., I.C.-H., D.C., H.C., S.C., V.C., R.D., F.D., M.F.-D., S. Gagneux, S. Ghebremichael, M.H., S.H., W.-w.J., S.K., I.K., T.L., S. Maeda, V.N., M.R., N.R., S.S., E.S.-P., B.S., I.C.S., A.S., L.-H.S., P. Stakenas, K.T., F.V., D.V., C.W. and R.W. obtained mycobacterial genotyping data and drug susceptibility test results.

Competing interests

P. Supply is a consultant for Genoscreen. C.A.-B. and C.W. were or are employees of the same company. The other authors declare no competing financial interests.

Corresponding authors

Correspondence to Philip Supply or Stefan Niemann or Thierry Wirth.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–10 and Supplementary Tables 2–10 and 12.

Excel files

  1. 1.

    Supplementary Table 1

    Genotyping results (24-locus MIRU-VNTR), country of origin, geolocalization and available phenotypic drug susceptibility test results for 4,987 analyzed clinical isolates from the MTBC Beijing lineage.

  2. 2.

    Supplementary Table 11

    Top Bayes factor variants. SNPs are given relative to the H37Rv reference sequence, and putative targets of selection are highlighted. The color codes along the logBF column correspond, respectively, to SNPs specific to the central Asia outbreak (blue), the European-Russian W148 outbreak (green) and the members of the modern Beijing lineage (orange).

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