%0 Journal Article
%T Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis
%A Abigail McGuire
%A Brian Weiner
%A Sang Park
%A Ilan Wapinski
%A Sahadevan Raman
%A Gregory Dolganov
%A Matthew Peterson
%A Robert Riley
%A Jeremy Zucker
%A Thomas Abeel
%A Jared White
%A Peter Sisk
%A Christian Stolte
%A Mike Koehrsen
%A Robert T Yamamoto
%A Milena Iacobelli-Martinez
%A Matthew J Kidd
%A Andreia M Maer
%A Gary K Schoolnik
%A Aviv Regev
%A James Galagan
%J BMC Genomics
%D 2012
%I BioMed Central
%R 10.1186/1471-2164-13-120
%X 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.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.Tuberculosis is still a major killer worldwide, causing an estimated 2-3 million deaths per year [1]. The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for a decade [2,3], but the biology of the pathogen remains poorly understood. Available genome sequences from Mtb strains and other closely related Mycobacteria present an opportunity to bring the power of comparative genomics to the study of Mtb.We report here the results of a comparative analysis of 31 publicly available genomes (http://www.tbdb.org webcite, Figure 1, Table 1). These include eight closely related members of the Mtb complex that can cause tuberculosis disease, (two M. bovis strains and six Mtb strains). Another 11 additional Mycobacteria range from obligate parasites to free-living soil bacteria: M. leprae an
%K Comparative genomics
%K M. tuberculosis
%K SYNERGY
%K Small RNAs
%K Lipid metabolism
%K Molybdopterin
%K DNA repair
%U http://www.biomedcentral.com/1471-2164/13/120