title: Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.
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.
authors.affiliation: Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA. amcguire@broadinstitute.org
authors.forename: Abigail Manson
authors.initials: AM
authors.lastname: McGuire
authors.forename: Brian
authors.initials: B
authors.lastname: Weiner
authors.forename: Sang Tae
authors.initials: ST
authors.lastname: Park
authors.forename: Ilan
authors.initials: I
authors.lastname: Wapinski
authors.forename: Sahadevan
authors.initials: S
authors.lastname: Raman
authors.forename: Gregory
authors.initials: G
authors.lastname: Dolganov
authors.forename: Matthew
authors.initials: M
authors.lastname: Peterson
authors.forename: Robert
authors.initials: R
authors.lastname: Riley
authors.forename: Jeremy
authors.initials: J
authors.lastname: Zucker
authors.forename: Thomas
authors.initials: T
authors.lastname: Abeel
authors.forename: Jared
authors.initials: J
authors.lastname: White
authors.forename: Peter
authors.initials: P
authors.lastname: Sisk
authors.forename: Christian
authors.initials: C
authors.lastname: Stolte
authors.forename: Mike
authors.initials: M
authors.lastname: Koehrsen
authors.forename: Robert T
authors.initials: RT
authors.lastname: Yamamoto
authors.forename: Milena
authors.initials: M
authors.lastname: Iacobelli-Martinez
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kidd
authors.forename: Andreia M
authors.initials: AM
authors.lastname: Maer
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schoolnik
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: James
authors.initials: J
authors.lastname: Galagan
mesh_terms: D039903:Actinobacteria / Q000145:classification / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003067:Coenzymes / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D023281:Genomics; D050356:Lipid Metabolism / Q000235:genetics; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism; D000090006:Molybdenum Cofactors; D009161:Mycobacterium / Q000145:classification / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D011621:Pteridines / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003067:Coenzymes; D005227:Fatty Acids; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; D022661:RNA, Untranslated; C022261:molybdopterin