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

BMC Genomics

Research Article

Jeremy Zucker¹  Jared White¹  Peter Sisk¹  Brian Weiner¹  Mike Koehrsen¹  Aviv Regev¹  Christian Stolte¹  James Galagan²  Ilan Wapinski³  Abigail Manson McGuire⁴  Thomas Abeel⁵  Robert Riley⁶  Matthew Peterson⁷  Sang Tae Park⁸  Sahadevan Raman⁸  Milena Iacobelli-Martinez⁹  Matthew J Kidd⁹  Robert T Yamamoto⁹  Andreia M Maer⁹  Gary K Schoolnik^1,10  Gregory Dolganov^1,10 

[1] Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;Department of Biomedical Engineering, Boston University, Boston, MA, USA;Departments of Microbiology and National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA;Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;Department of Systems Biology, Harvard Medical School, 200 Longwood Ave., 02115, Boston, MA, USA;Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;The Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;Broad Institute, 7 Cambridge Center, 02142, Cambridge, MA, USA;VIB Department of Plant Systems Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium;DOE Joint Genome Institute, Walnut Creek, CA, USA;Department of Biomedical Engineering, Boston University, Boston, MA, USA;Departments of Microbiology and National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA;FLIR, Chem-Bio Detection, 505 Coast Boulevard South, Suite 309, 92037, La Jolla, CA, USA;Stanford University, Palo Alto, CA, USA;

关键词: Comparative genomics;    M. tuberculosis;    SYNERGY;    Small RNAs;    Lipid metabolism;    Molybdopterin;    DNA repair;   

DOI  :  10.1186/1471-2164-13-120

 received in 2011-09-23, accepted in 2012-03-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsOur 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© McGuire et al; licensee BioMed Central Ltd. 2012