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Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains

Laurence Rohmer1*, Christine Fong1, Simone Abmayr1, Michael Wasnick1, Theodore J Larson Freeman1, Matthew Radey1, Tina Guina2, Kerstin Svensson34, Hillary S Hayden5, Michael Jacobs5, Larry A Gallagher1, Colin Manoil1, Robert K Ernst6, Becky Drees7, Danielle Buckley5, Eric Haugen5, Donald Bovee5, Yang Zhou5, Jean Chang5, Ruth Levy5, Regina Lim5, Will Gillett5, Don Guenthener5, Allison Kang5, Scott A Shaffer8, Greg Taylor8, Jinzhi Chen8, Byron Gallis8, David A D'Argenio7, Mats Forsman3, Maynard V Olson156, David R Goodlett8, Rajinder Kaul56, Samuel I Miller167 and Mitchell J Brittnacher1

Author Affiliations

1 Department of Genome Sciences, University of Washington, Campus Box 357710, 1705 NE Pacific street Seattle, Washington 98195, USA

2 Department of Pediatrics, Division of Infectious Diseases, University of Washington, Campus Box 357710, 1720 NE Pacific street, Seattle, Washington 98195, USA

3 NBC Analysis, Division of NBC Defence, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden

4 Department of Clinical Microbiology, Infectious Diseases, Umeå University, SE-901 85 Umeå, Sweden

5 University of Washington Genome Center, University of Washington, Campus Box 352145, Mason Road, Seattle, Washington 98195, USA

6 Department Medicine, University of Washington, Seattle, Washington 98195, USA

7 Department of Microbiology, University of Washington, Box 357242, 1720 NE Pacific street, Seattle, Washington 98195, USA

8 Department of Medicinal Chemistry, Box 357610, University of Washington, Seattle, Washington 98195, USA

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Genome Biology 2007, 8:R102  doi:10.1186/gb-2007-8-6-r102

Published: 5 June 2007



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.


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.


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.