title: A non-sense mutation in the putative anti-mutator gene ada/alkA of Mycobacterium tuberculosis and M. bovis isolates suggests convergent evolution.
abstract: BACKGROUND
  Previous studies have suggested that variations in DNA repair genes of W-Beijing strains may have led to transient mutator phenotypes which in turn may have contributed to host adaptation of this strain family. Single nucleotide polymorphism (SNP) in the DNA repair gene mutT1 was identified in MDR-prone strains from the Central African Republic. A Mycobacteriumtuberculosis H37Rv mutant inactivated in two DNA repair genes, namely ada/alkA and ogt, was shown to display a hypermutator phenotype. We then looked for polymorphisms in these genes in Central African Republic strains (CAR).
  
  
  RESULTS
  In this study, 55 MDR and 194 non-MDR strains were analyzed. Variations in DNA repair genes ada/alkA and ogt were identified. Among them, by comparison to M. tuberculosis published sequences, we found a non-sense variation in ada/alkA gene which was also observed in M. bovis AF2122 strain. SNPs that are present in the adjacent regions to the amber variation are different in M. bovis and in M. tuberculosis strain.
  
  
  CONCLUSIONS
  An Amber codon was found in the ada/alkA locus of clustered M. tuberculosis isolates and in M. bovis strain AF2122. This is likely due to convergent evolution because SNP differences between strains are incompatible with horizontal transfer of an entire gene. This suggests that such a variation may confer a selective advantage and be implicated in hypermutator phenotype expression, which in turn contributes to adaptation to environmental changes.
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris Cedex, France. x.nouvel@envt.fr <x.nouvel@envt.fr>
authors.forename: Laurent X
authors.initials: LX
authors.lastname: Nouvel
authors.forename: Tiago
authors.initials: T
authors.lastname: Dos Vultos
authors.forename: Eric
authors.initials: E
authors.lastname: Kassa-Kelembho
authors.forename: Jean
authors.initials: J
authors.lastname: Rauzier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D002488:Central African Republic; D018389:Codon, Nonsense / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D009163:Mycobacterium bovis / Q000235:genetics* / Q000302:isolation & purification; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D018389:Codon, Nonsense; D045643:DNA Repair Enzymes