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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.

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis