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Related Experiment Videos

Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis

David Alland1, Thomas S Whittam, Megan B Murray

  • 1Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Newark, New Jersey 07103, USA. allandda@umdnj.edu

Journal of Bacteriology
|May 20, 2003
PubMed
Summary

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Comparative-genomic sequencing identified single nucleotide polymorphism (SNP) markers for Mycobacterium tuberculosis evolution. These markers reveal a highly clonal bacterial species with limited lateral gene exchange and potential evolutionary bottlenecks.

Area of Science:

  • Genomics
  • Evolutionary Biology
  • Microbiology

Background:

  • Comparative-genomic sequencing of Mycobacterium tuberculosis (M. tuberculosis) strains can identify markers for evolutionary and epidemiological studies.
  • Phylogenetic analysis using comparative-genome markers (CGMs) has yielded unusual M. tuberculosis phylogenies lacking secondary branches.

Purpose of the Study:

  • To investigate the properties of CGMs and their impact on phylogenetic analysis.
  • To reconstruct the evolutionary history of M. tuberculosis using refined CGM methodology.

Main Methods:

  • Devised computer models to simulate sequence evolution and phylogenetic calculations based on single nucleotide polymorphism (SNP) data.
  • Analyzed M. tuberculosis phylogenies using CGMs, considering the genetic distances between reference strains.

Related Experiment Videos

  • Examined population-based evidence for specific genetic polymorphisms and IS6110 element copy numbers.

    • Main Results:

    • CGMs are a distinct class of phylogenetic markers critically dependent on the genetic distance between reference strains.
    • Properly selected reference strains yield accurate CGMs, while improperly selected ones distort phylogenetic signals.
    • M. tuberculosis appears highly clonal with minimal lateral gene exchange, exhibiting evolutionary bottlenecks and specific genetic patterns like IS6110 loss and KasA polymorphisms.

    Conclusions:

    • CGMs can accurately reflect evolutionary relationships when reference strains are appropriately chosen.
    • The M. tuberculosis species exhibits a clonal structure, suggesting limited horizontal gene transfer.
    • Evidence suggests evolutionary bottlenecks and selective pressures acting on specific genes like KasA.