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A new evolutionary scenario for the Mycobacterium tuberculosis complex.

R Brosch1, S V Gordon, M Marmiesse

  • 1Unité de Génétique Moléculaire Bactérienne, Laboratoire de Génomique des Microorganismes Pathogènes, and Centre National de Référence des Mycobactéries, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.

Proceedings of the National Academy of Sciences of the United States of America
|March 14, 2002
PubMed
Summary

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Genetic analysis of 100 tubercle bacilli strains reveals that Mycobacterium tuberculosis likely evolved from a human pathogen, not Mycobacterium bovis. Ancient deletions shaped the Mycobacterium tuberculosis complex evolution.

Area of Science:

  • Genomics
  • Evolutionary Biology
  • Microbiology

Background:

  • The evolutionary history of Mycobacterium tuberculosis complex (MTC) strains, including Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium canettii, Mycobacterium microti, and Mycobacterium bovis, is debated.
  • Previous hypotheses suggested Mycobacterium tuberculosis evolved from Mycobacterium bovis, the agent of bovine tuberculosis.

Purpose of the Study:

  • To investigate the evolutionary relationships within the Mycobacterium tuberculosis complex.
  • To determine the origins and evolutionary trajectory of Mycobacterium tuberculosis strains.

Main Methods:

  • Genomic analysis of 20 variable regions resulting from insertion-deletion events.
  • Evaluation of 100 strains from five species: M. tuberculosis, M. africanum, M. canettii, M. microti, and M. bovis.

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  • Identification and characterization of specific deletions, such as TbD1 and Region of Difference 9 (RD9).

    • Main Results:

    • The majority of polymorphisms in MTC strains originated from ancient genetic events in common progenitors, not independent occurrences.
    • Mycobacterium tuberculosis strains were classified into ancestral and 'modern' types based on the TbD1 deletion.
    • An evolutionary lineage including M. africanum, M. microti, and M. bovis showed successive DNA loss, diverging before the TbD1 deletion event.

    Conclusions:

    • Findings contradict the hypothesis that Mycobacterium tuberculosis evolved from Mycobacterium bovis.
    • Mycobacterium canettii and ancestral Mycobacterium tuberculosis strains appear to be direct descendants of earlier tubercle bacilli.
    • The common ancestor of tubercle bacilli likely resembled Mycobacterium tuberculosis or Mycobacterium canettii and may have been a human pathogen.