title: Plasmid diversity and phylogenetic consistency in the Lyme disease agent Borrelia burgdorferi.
abstract: Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.
  
  
  
  We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination events. We identify 32 different putative plasmid compatibility types among the 236 plasmids, of which 15 are (usually) circular and 17 are linear. Because of past rearrangements, any given gene, even though it might be universally present in these isolates, is often found on different linear plasmid compatibility types in different isolates. For example, the arp gene and the vls cassette region are present on plasmids of four and five different compatibility types, respectively, in different isolates. A majority of the plasmid types have more than one organizationally different subtype, and the number of such variants ranges from one to eight among the 18 linear plasmid types. In spite of this substantial organizational diversity, the plasmids are not so variable that every isolate has a novel version of every plasmid (i.e., there appears to be a limited number of extant plasmid subtypes).
  
  
  
  Although there have been many past recombination events, both homologous and nonhomologous, among the plasmids, particular organizational variants of these plasmids correlate with particular chromosomal genotypes, suggesting that there has not been rapid horizontal transfer of whole linear plasmids among B. burgdorferi lineages. We argue that plasmid rearrangements are essentially non-revertable and are present at a frequency of only about 0.65% that of single nucleotide changes, making rearrangement-derived novel junctions (mosaic boundaries) ideal phylogenetic markers in the study of B. burgdorferi population structure and plasmid evolution and exchange.
authors.affiliation: Division of Microbiology and Immunology, Pathology Department and Biology Department, University of Utah School of Medicine, Room 2200 K Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT, 84112, USA. sherwood.casjens@path.utah.edu.|Biology Department, University of Utah, Salt Lake City, UT, USA. sherwood.casjens@path.utah.edu.
authors.forename: Sherwood R
authors.initials: SR
authors.lastname: Casjens
authors.affiliation: Division of Microbiology and Immunology, Pathology Department and Biology Department, University of Utah School of Medicine, Room 2200 K Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT, 84112, USA.
authors.forename: Eddie B
authors.initials: EB
authors.lastname: Gilcrease
authors.affiliation: Division of Microbiology and Immunology, Pathology Department and Biology Department, University of Utah School of Medicine, Room 2200 K Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT, 84112, USA.|Present Address: Janssen Disease and Vaccines, Pharmaceutical Companies of Johnson and Johnson, Leiden, The Netherlands.
authors.forename: Marija
authors.initials: M
authors.lastname: Vujadinovic
authors.affiliation: Institute for Genome Sciences, University of Maryland BioPark, Baltimore, MD, USA.
authors.forename: Emmanuel F
authors.initials: EF
authors.lastname: Mongodin
authors.affiliation: Department of Medicine, Health Science Center, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Luft
authors.affiliation: Department of Medicine, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, 07103, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schutzer
authors.affiliation: Institute for Genome Sciences, University of Maryland BioPark, Baltimore, MD, USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.affiliation: Department of Biology, The Graduate Center, City University of New York City, New York, NY, USA.|Department of Biological Sciences and Center for Translational and Basic Research, Hunter College of the City University of New York City, New York, NY, USA.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Qiu
mesh_terms: D025065:Borrelia burgdorferi / Q000235:genetics* / Q000502:physiology*; D002876:Chromosomes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics; D023281:Genomics; D008193:Lyme Disease / Q000382:microbiology*; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics*
keywords: B. burgdorferi; Genome rearrangement; Linear plasmid; Plasmid