title: Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level.
abstract: BACKGROUND
  Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background.
  
  
  RESULTS
  Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains.
  
  
  CONCLUSIONS
  This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus.
authors.affiliation: Programs in Genomics and Vector-borne Diseases, Department of Veterinary Microbiology & Pathology and Paul G, Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, USA. laua@vetmed.wsu.edu
authors.forename: Audrey Ot
authors.initials: AO
authors.lastname: Lau
authors.forename: Ananth
authors.initials: A
authors.lastname: Kalyanaraman
authors.forename: Ignacio
authors.initials: I
authors.lastname: Echaide
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Russell
authors.initials: R
authors.lastname: Bock
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Pedroni
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rameshkumar
authors.forename: Mariano B
authors.initials: MB
authors.lastname: Ferreira
authors.forename: Taryn I
authors.initials: TI
authors.lastname: Fletcher
authors.forename: Terry F
authors.initials: TF
authors.lastname: McElwain
mesh_terms: D000818:Animals; D016793:Babesia bovis / Q000235:genetics* / Q000472:pathogenicity*; D001769:Blood / Q000469:parasitology*; D014644:Genetic Variation / Q000235:genetics*; D023281:Genomics; D005843:Geography; D010641:Phenotype; D017421:Sequence Analysis; D013045:Species Specificity