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Open Access Research article

Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice

Roger M Wanner1, Carolin Güthlein1, Burkhard Springer2, Erik C Böttger1 and Martin Ackermann3*

Author Affiliations

1 Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastrasse 30/32, CH-8006 Zürich, Switzerland

2 Institute of Medical Microbiology and Hygiene Graz, Austrian Agency for Health and Food Safety, Beethovenstrasse 6, A-8010 Graz, Austria

3 Institute of Integrative Biology, ETH Zurich, Universitaetsstrasse 16, CH-8092 Zürich, Switzerland

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BMC Genomics 2008, 9:249  doi:10.1186/1471-2164-9-249

Published: 28 May 2008



The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable.


We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability.


These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.