title: Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.
abstract: BACKGROUND
  Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans.
  
  
  RESULTS
  Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation.
  
  
  CONCLUSIONS
  The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.
authors.affiliation: Department of Genome Sciences, University of Washington, Campus Box 357710, 1705 NE Pacific street Seattle, Washington 98195, USA. lrohmer@u.washington.edu
authors.forename: Laurence
authors.initials: L
authors.lastname: Rohmer
authors.forename: Christine
authors.initials: C
authors.lastname: Fong
authors.forename: Simone
authors.initials: S
authors.lastname: Abmayr
authors.forename: Michael
authors.initials: M
authors.lastname: Wasnick
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Larson Freeman
authors.forename: Matthew
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authors.lastname: Radey
authors.forename: Tina
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authors.lastname: Guina
authors.forename: Kerstin
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authors.lastname: Svensson
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobs
authors.forename: Larry A
authors.initials: LA
authors.lastname: Gallagher
authors.forename: Colin
authors.initials: C
authors.lastname: Manoil
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: Becky
authors.initials: B
authors.lastname: Drees
authors.forename: Danielle
authors.initials: D
authors.lastname: Buckley
authors.forename: Eric
authors.initials: E
authors.lastname: Haugen
authors.forename: Donald
authors.initials: D
authors.lastname: Bovee
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jean
authors.initials: J
authors.lastname: Chang
authors.forename: Ruth
authors.initials: R
authors.lastname: Levy
authors.forename: Regina
authors.initials: R
authors.lastname: Lim
authors.forename: Will
authors.initials: W
authors.lastname: Gillett
authors.forename: Don
authors.initials: D
authors.lastname: Guenthener
authors.forename: Allison
authors.initials: A
authors.lastname: Kang
authors.forename: Scott A
authors.initials: SA
authors.lastname: Shaffer
authors.forename: Greg
authors.initials: G
authors.lastname: Taylor
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Chen
authors.forename: Byron
authors.initials: B
authors.lastname: Gallis
authors.forename: David A
authors.initials: DA
authors.lastname: D'Argenio
authors.forename: Mats
authors.initials: M
authors.lastname: Forsman
authors.forename: Maynard V
authors.initials: MV
authors.lastname: Olson
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Rajinder
authors.initials: R
authors.lastname: Kaul
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Brittnacher
mesh_terms: D004251:DNA Transposable Elements; D019143:Evolution, Molecular; D005604:Francisella tularensis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D016680:Genome, Bacterial; D006801:Humans; D009154:Mutation; D011544:Pseudogenes; D014774:Virulence
chemical_list: D004251:DNA Transposable Elements