Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.
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.
Rohmer
Laurence
L
Department of Genome Sciences, University of Washington, Campus Box 357710, 1705 NE Pacific street Seattle, Washington 98195, USA. lrohmer@u.washington.edu
Fong
Christine
C
Abmayr
Simone
S
Wasnick
Michael
M
Larson Freeman
Theodore J
TJ
Radey
Matthew
M
Guina
Tina
T
Svensson
Kerstin
K
Hayden
Hillary S
HS
Jacobs
Michael
M
Gallagher
Larry A
LA
Manoil
Colin
C
Ernst
Robert K
RK
Drees
Becky
B
Buckley
Danielle
D
Haugen
Eric
E
Bovee
Donald
D
Zhou
Yang
Y
Chang
Jean
J
Levy
Ruth
R
Lim
Regina
R
Gillett
Will
W
Guenthener
Don
D
Kang
Allison
A
Shaffer
Scott A
SA
Taylor
Greg
G
Chen
Jinzhi
J
Gallis
Byron
B
D'Argenio
David A
DA
Forsman
Mats
M
Olson
Maynard V
MV
Goodlett
David R
DR
Kaul
Rajinder
R
Miller
Samuel I
SI
Brittnacher
Mitchell J
MJ
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
D004251:DNA Transposable Elements