title: Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids.
abstract: Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. sherwood.casjens@path.utah.edu
authors.forename: Sherwood R
authors.initials: SR
authors.lastname: Casjens
authors.forename: Emmanuel F
authors.initials: EF
authors.lastname: Mongodin
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Qiu
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Luft
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schutzer
authors.forename: Eddie B
authors.initials: EB
authors.lastname: Gilcrease
authors.forename: Wai Mun
authors.initials: WM
authors.lastname: Huang
authors.forename: Marija
authors.initials: M
authors.lastname: Vujadinovic
authors.forename: John K
authors.initials: JK
authors.lastname: Aron
authors.forename: Levy C
authors.initials: LC
authors.lastname: Vargas
authors.forename: Sam
authors.initials: S
authors.lastname: Freeman
authors.forename: Diana
authors.initials: D
authors.lastname: Radune
authors.forename: Janice F
authors.initials: JF
authors.lastname: Weidman
authors.forename: George I
authors.initials: GI
authors.lastname: Dimitrov
authors.forename: Hoda M
authors.initials: HM
authors.lastname: Khouri
authors.forename: Julia E
authors.initials: JE
authors.lastname: Sosa
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Halpin
authors.forename: John J
authors.initials: JJ
authors.lastname: Dunn
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000302:isolation & purification; D002876:Chromosomes, Bacterial / Q000235:genetics; D004269:DNA, Bacterial / Q000378:metabolism; D014644:Genetic Variation; D016680:Genome, Bacterial; D042822:Genomic Instability / Q000235:genetics*; D023281:Genomics; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology*; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010957:Plasmids / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial