title: Natural Selection in Virulence Genes of Francisella tularensis.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, 84602, USA. mark.k.gunnell2.civ@mail.mil.|Microbiology Branch, Life Sciences Division, Dugway Proving Ground, Dugway, UT, 84022, USA. mark.k.gunnell2.civ@mail.mil.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Gunnell
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Robison
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, 84602, USA.
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Adams
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics; D005604:Francisella tularensis / Q000235:genetics* / Q000472:pathogenicity*; D005787:Gene Frequency; D016680:Genome, Bacterial; D012641:Selection, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins
keywords: Francisella tularensis; Genome decay; Natural selection; TreeSAAP; Virulence