title: Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B (OSU18) genome sequence.
abstract: The gamma-proteobacterium Francisella tularensis is one of the most infectious human pathogens, and the highly virulent organism F. tularensis subsp. tularensis (type A) and less virulent organism F. tularensis subsp. holarctica (type B) are most commonly associated with significant disease in humans and animals. Here we report the complete genome sequence and annotation for a low-passage type B strain (OSU18) isolated from a dead beaver found near Red Rock, Okla., in 1978. A comparison of the F. tularensis subsp. holarctica sequence with that of F. tularensis subsp. tularensis strain Schu4 (P. Larsson et al., Nat. Genet. 37:153-159, 2005) highlighted genetic differences that may underlie different pathogenicity phenotypes and the evolutionary relationship between type A and type B strains. Despite extensive DNA sequence identity, the most significant difference between type A and type B isolates is the striking amount of genomic rearrangement that exists between the strains. All but two rearrangements can be attributed to homologous recombination occurring between two prominent insertion elements, ISFtu1 and ISFtu2. Numerous pseudogenes have been found in the genomes and are likely contributors to the difference in virulence between the strains. In contrast, no rearrangements have been observed between the OSU18 genome and the genome of the type B live vaccine strain (LVS), and only 448 polymorphisms have been found within non-transposase-coding sequences whose homologs are intact in OSU18. Nonconservative differences between the two strains likely include the LVS attenuating mutation(s).
authors.affiliation: Department of Molecular Virology and Microbiology, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, BCM280, Houston, TX 77030, USA. jpetrosi@bcm.edu
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiang
authors.forename: Sandor E
authors.initials: SE
authors.lastname: Karpathy
authors.forename: Huaiyang
authors.initials: H
authors.lastname: Jiang
authors.forename: Shailaja
authors.initials: S
authors.lastname: Yerrapragada
authors.forename: Yamei
authors.initials: Y
authors.lastname: Liu
authors.forename: Jason
authors.initials: J
authors.lastname: Gioia
authors.forename: Lisa
authors.initials: L
authors.lastname: Hemphill
authors.forename: Arely
authors.initials: A
authors.lastname: Gonzalez
authors.forename: T M
authors.initials: TM
authors.lastname: Raghavan
authors.forename: Akif
authors.initials: A
authors.lastname: Uzman
authors.forename: George E
authors.initials: GE
authors.lastname: Fox
authors.forename: Sarah
authors.initials: S
authors.lastname: Highlander
authors.forename: Mason
authors.initials: M
authors.lastname: Reichard
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Morton
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Clinkenbeard
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
mesh_terms: D002876:Chromosomes, Bacterial / Q000235:genetics*; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005604:Francisella tularensis / Q000235:genetics*; D015321:Gene Rearrangement; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011544:Pseudogenes; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014774:Virulence / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D004269:DNA, Bacterial