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Comparative Study
. 2007;8(6):R102.
doi: 10.1186/gb-2007-8-6-r102.

Comparison of Francisella Tularensis Genomes Reveals Evolutionary Events Associated With the Emergence of Human Pathogenic Strains

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Free PMC article
Comparative Study

Comparison of Francisella Tularensis Genomes Reveals Evolutionary Events Associated With the Emergence of Human Pathogenic Strains

Laurence Rohmer et al. Genome Biol. .
Free PMC article

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.

Conclusion: 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.

Figures

Figure 1
Figure 1
The alignment of the genomes reveals multiple genomic rearrangements probably mediated by IS elements. Each genome was aligned against each of the others using Nucmer (see Materials and methods). Horizontal and vertical lines represent the location of the IS elements in the compared genomes. The breakpoints of the syntenic blocks in the subspecies holarctica and tularensis are often associated with IS elements, whereas IS elements do not border most syntenic blocks in the genome of novicida. bp, base pairs; F.t., Francisella tularensis; IS, insertion sequences; LVS, live vaccine strain.
Figure 2
Figure 2
The distribution of pseudogenes is uneven in the genome and across functional categories. (a) Pseudogenes are more likely to be found near genomic breakpoints than in the rest of the genome. B. Genes inactivated both in Schu S4 and live vaccine strain (LVS) and sharing the same inactivating mutation are more likely to be near a genomic breakpoint than those not sharing the same inactivating mutation. (c) Missing and inactivated genes in the genomes of Francisella tularensis subspecies tularensis (F.t.t.) Schu S4 and Francisella tularensis subspecies holarctica (F.t.h.) LVS are not evenly distributed across functional categories. F.t.n., Francisella tularensis subspecies novicida; kb, kilobases; LPS, lipopolysaccharide.
Figure 3
Figure 3
Inactivating mutations in two operons illustrate the ongoing process of gene decay. The leu operon and the ilv operon, which work in concert, accumulated inactivating mutations in the genome of Francisella tularensis subspecies tularensis (F.t.t.) Schu S4 and F tularensis subspecies holarctica (F.t.h.) live vaccine strain (LVS). The ISFtu1 element that disrupted leuA and the ISFtu1 integrated upstream of leuB share the same bordering sequences in both genomes. The inactivating mutation in leuB is the same in both genomes as well. Therefore, these events are believed to have taken place in the leu operon before divergence into two subspecies. The other mutations in the regions of the leu operon and the ilv operon are of different origins in the two genomes, indicating that these mutations took place after the subspeciation.

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