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Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans

Nature Genetics 45, 1176–1182 (2013) | Download Citation

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Abstract

Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities.

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European Nucleotide Archive

Sequence Read Archive

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Acknowledgements

We thank D. Behar and S. Rosset for providing the mitochondrial genome sequences and C. Gignoux for advice on the mitochondrial Neolithic data set, N. Mistry (The Foundation for Medical Research) for providing bacterial strains and C. Dye, F. Balloux and L. Weinert for comments on the manuscript. This work was supported by the MRC UK (grants U.1175.02.002.00015.01 to S.G. and U117581288 to D.Y.), the Swiss National Science Foundation (PP0033-119205 to S.G.), the US National Institutes of Health (AI090928 and HHSN266200700022C to S.G.), the Leverhulme-Royal Society Africa Award (AA080019 to S.G.) and the Natural Science Foundation of China (grant 91231115 to Q.G.). DNA sequencing was partially supported by core funding of the Wellcome Trust (grant 098051) and by a Framework Programme 7 project of the European Community (SysteMTb HEALTH-F4-2010-241587 to D.Y.). I.C. is supported by European Union funding from the Marie Curie Framework Programme 7 actions (project 272086) and project BFU2011-24112 from the Ministerio de Economía y Competitividad (Spain).

Author information

    • Mireia Coscolla
    •  & Tao Luo

    These authors contributed equally to this work.

    • Douglas Young
    •  & Sebastien Gagneux

    These authors jointly directed this work.

Affiliations

  1. Genomics and Health Unit, Centre for Public Health Research (CSISP-FISABIO), Valencia, Spain.

    • Iñaki Comas

  2. CIBER (Centros de Investigación Biomédica en Red) in Epidemiology and Public Health, Barcelona, Spain.

    • Iñaki Comas

  3. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

    • Mireia Coscolla
    • , Sonia Borrell
    • , Bijaya Malla
    •  & Sebastien Gagneux

  4. University of Basel, Basel, Switzerland.

    • Mireia Coscolla
    • , Sonia Borrell
    • , Bijaya Malla
    •  & Sebastien Gagneux

  5. Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.

    • Tao Luo
    •  & Qian Gao

  6. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Victoria, Australia.

    • Kathryn E Holt

  7. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.

    • Kathryn E Holt

  8. Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California, USA.

    • Midori Kato-Maeda

  9. Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Julian Parkhill
    • , Stephen Bentley
    •  & Simon R Harris

  10. TB Research Group, Veterinary Laboratories Agency, Weybridge, New Haw and Addlestone, UK.

    • Stefan Berg

  11. Department of Infectious Disease, King's College London, London, UK.

    • Guy Thwaites

  12. Centre for Clinical Infection and Diagnostics Research, King's College London, London, UK.

    • Guy Thwaites

  13. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.

    • Dorothy Yeboah-Manu

  14. Department of Respiratory Medicine, Homerton University Hospital, London, UK.

    • Graham Bothamley

  15. Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

    • Jian Mei

  16. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

    • Lanhai Wei

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

    • Stefan Niemann

  18. Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Germany.

    • Roland Diel

  19. Armauer Hansen Research Institute, Addis Ababa, Ethiopia.

    • Abraham Aseffa

  20. Medical Research Council (MRC) National Institute for Medical Research, Mill Hill, London, UK.

    • Douglas Young

  21. Department of Medicine, Imperial College London, London, UK.

    • Douglas Young

  22. Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.

    • Douglas Young

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Contributions

I.C., Q.G., D.Y. and S.G. designed and supervised the study. M.C., S. Borrell, K.E.H., M.K.-M., J.P., B.M., S. Berg, G.T., D.Y.-M., G.B., J.M., L.W., S.R.H., S.N., R.D., A.A., Q.G. and S.G. provided MTBC strains and/or reagents. J.P., S. Bentley and S.R.H. contributed to the genome sequencing. I.C., M.C. and T.L. analyzed the data. I.C., M.C., T.L., S. Borrell, K.E.H., J.P., S. Berg, G.T., D.Y.-M., S. Bentley, S.R.H., S.N., A.A., Q.G., D.Y. and S.G. contributed to the manuscript writing. All authors read and approved the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Iñaki Comas or Qian Gao or Sebastien Gagneux.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–10, Supplementary Table 7 and Supplementary Note

Excel files

  1. 1.

    Supplementary Table 1

    List of mycobacterial strains used in this study

  2. 2.

    Supplementary Table 2

    Variable single nucleotide positions in the 219 MTBC dataset (excluding outgroup)

  3. 3.

    Supplementary Table 3

    Accession number and haplogroup of the 4,955 human mitochondrial (mtDNA) genomes reference dataset

  4. 4.

    Supplementary Table 4

    MTBC strains and human mtDNA genomes used to test for the statistical association

  5. 5.

    Supplementary Table 5

    Accession number, haplogroup and prehistoric period of the 423 human mtDNA genomes obtained from Gignoux et al. 2011

  6. 6.

    Supplementary Table 6

    Accession number and haplogroup of the human mtDNA genomes used for the analysis of the Neolithic in East Asia

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DOI

https://doi.org/10.1038/ng.2744

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