Journal of Molecular Evolution

, Volume 82, Issue 6, pp 264–278 | Cite as

Natural Selection in Virulence Genes of Francisella tularensis

  • Mark K. GunnellEmail author
  • Richard A. Robison
  • Byron J. Adams
Original Article


A fundamental tenet of evolution is that alleles that are under negative selection are often deleterious and confer no evolutionary advantage. Negatively selected alleles are removed from the gene pool and are eventually extinguished from the population. Conversely, alleles under positive selection do confer an evolutionary advantage and lead to an increase in the overall fitness of the organism. These alleles increase in frequency until they eventually become fixed in the population. Francisella tularensis is a zoonotic pathogen and a potential biothreat agent. The most virulent type of F. tularensis, Type A, is distributed across North America with Type A.I occurring mainly in the east and Type A.II appearing mainly in the west. F. tularensis is thought to be a genome in decay (losing genes) because of the relatively large number of pseudogenes present in its genome. We hypothesized that the observed frequency of gene loss/pseudogenes may be an artifact of evolution in response to a changing environment, and that genes involved in virulence should be under strong positive selection. To test this hypothesis, we sequenced and compared whole genomes of Type A.I and A.II isolates. We analyzed a subset of virulence and housekeeping genes from several F. tularensis subspecies genomes to ascertain the presence and extent of positive selection. Eleven previously identified virulence genes were screened for positive selection along with 10 housekeeping genes. Analyses of selection yielded one housekeeping gene and 7 virulence genes which showed significant evidence of positive selection at loci implicated in cell surface structures and membrane proteins, metabolism and biosynthesis, transcription, translation and cell separation, and substrate binding and transport. Our results suggest that while the loss of functional genes through disuse could be accelerated by negative selection, the genome decay in Francisella could also be the byproduct of adaptive evolution driven by complex interactions between host, pathogen, and thier environment, as evidenced by several of its virulence genes which are undergoing strong, positive selection.


Francisella tularensis Genome decay Natural selection TreeSAAP Virulence 



We thank the Utah Department of Health and the New Mexico Department of Health for help in obtaining the isolates used in this study, and for the thoughtful and constructive criticisms of the anonymous reviewers. Dr. Angelo Madonna of Dugway Proving Ground provided expert guidance and assistance in completing this work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mark K. Gunnell
    • 1
    • 2
    Email author
  • Richard A. Robison
    • 1
  • Byron J. Adams
    • 3
  1. 1.Department of Microbiology and Molecular BiologyBrigham Young UniversityProvoUSA
  2. 2.Microbiology Branch, Life Sciences DivisionDugway Proving GroundDugwayUSA
  3. 3.Department of BiologyBrigham Young UniversityProvoUSA

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