BMC Genomics (Mar 2012)

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of <it>mycobacterium tuberculosis </it>pathogenesis

  • McGuire Abigail,
  • Weiner Brian,
  • Park Sang,
  • Wapinski Ilan,
  • Raman Sahadevan,
  • Dolganov Gregory,
  • Peterson Matthew,
  • Riley Robert,
  • Zucker Jeremy,
  • Abeel Thomas,
  • White Jared,
  • Sisk Peter,
  • Stolte Christian,
  • Koehrsen Mike,
  • Yamamoto Robert T,
  • Iacobelli-Martinez Milena,
  • Kidd Matthew J,
  • Maer Andreia M,
  • Schoolnik Gary K,
  • Regev Aviv,
  • Galagan James

DOI
https://doi.org/10.1186/1471-2164-13-120
Journal volume & issue
Vol. 13, no. 1
p. 120

Abstract

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Abstract Background The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Results Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Conclusions Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

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