Limits...
Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids.

Casjens SR, Mongodin EF, Qiu WG, Luft BJ, Schutzer SE, Gilcrease EB, Huang WM, Vujadinovic M, Aron JK, Vargas LC, Freeman S, Radune D, Weidman JF, Dimitrov GI, Khouri HM, Sosa JE, Halpin RA, Dunn JJ, Fraser CM - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. sherwood.casjens@path.utah.edu

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.

Show MeSH

Related in: MedlinePlus

Comparison of lp28-1 plasmids and the vls cassette and vlsE loci.Percent G+C plots for the plasmids were created by DNA Strider [135]. Different background color indicates very different sequence in the different plasmids (note that the partition gene regions in the two lp28-1 plasmids are homologous, but moderately divergent from those of lp36; see text).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3303823&req=5

pone-0033280-g005: Comparison of lp28-1 plasmids and the vls cassette and vlsE loci.Percent G+C plots for the plasmids were created by DNA Strider [135]. Different background color indicates very different sequence in the different plasmids (note that the partition gene regions in the two lp28-1 plasmids are homologous, but moderately divergent from those of lp36; see text).

Mentions: The B31 plasmid lp28-1 has received considerable attention because it carries two genes, arp (b31_f01) and vlsE (near the left and right ends, respectively), that are important in the mouse model of Lyme borreliosis. Loss of lp28-1 severely reduces strain B31 infectivity in mice but not in ticks [81], [89], [115], [116], [121]–[124], and antibodies against the B31 Arp protein cause resolution of B. burgdorferi induced arthritis in mice [125]–[127]. N40 does not carry a plasmid with an lp28-1 PFam32 gene, and the JD1 and 297 lp28-1 plasmids are very similar to each other (99.5% identical over the nearly 15 Kbp), but are quite different from B31 lp28-1. These two lp28-1 types only have the partition genes and vls/vlsE region in common (Figures 5 and S2I). Between these two regions of the JD1 and 297 plasmids lies about 2.6 Kbp of DNA that contains a PFam106 gene (jd1_f23 and 297_f25) that is homologous to B31 lp38 genes b31_j23 and b31_j24. This JD1 protein is only about 40% identical to B31_J23 protein. At their left ends JD1 and 297 lp28-1s have about 6 Kbp that is about 99% identical to the right end extension of the B31 chromosome (above) and which contains an apparently intact PFam138 gene (b31_0852 in B31) and about 2.7 Kbp that has no ortholog in B31 and no convincing intact genes. The arp gene is not present on lp28-1 in the three new genomes discussed here. In N40 it is near the right end of lp28-5 (gene n40_y16), and in JD1 it is near the left end of lp28-4 (jd1_i37; and perhaps also in 297, although the sequence of the parallel region of its lp28-4 was not determined). The B31 and N40 Arp proteins are identical, and the JD1 homolog is 99.1% identical to them, so this movement of the arp gene among these different plasmids happened quite recently.


Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids.

Casjens SR, Mongodin EF, Qiu WG, Luft BJ, Schutzer SE, Gilcrease EB, Huang WM, Vujadinovic M, Aron JK, Vargas LC, Freeman S, Radune D, Weidman JF, Dimitrov GI, Khouri HM, Sosa JE, Halpin RA, Dunn JJ, Fraser CM - PLoS ONE (2012)

Comparison of lp28-1 plasmids and the vls cassette and vlsE loci.Percent G+C plots for the plasmids were created by DNA Strider [135]. Different background color indicates very different sequence in the different plasmids (note that the partition gene regions in the two lp28-1 plasmids are homologous, but moderately divergent from those of lp36; see text).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303823&req=5

pone-0033280-g005: Comparison of lp28-1 plasmids and the vls cassette and vlsE loci.Percent G+C plots for the plasmids were created by DNA Strider [135]. Different background color indicates very different sequence in the different plasmids (note that the partition gene regions in the two lp28-1 plasmids are homologous, but moderately divergent from those of lp36; see text).
Mentions: The B31 plasmid lp28-1 has received considerable attention because it carries two genes, arp (b31_f01) and vlsE (near the left and right ends, respectively), that are important in the mouse model of Lyme borreliosis. Loss of lp28-1 severely reduces strain B31 infectivity in mice but not in ticks [81], [89], [115], [116], [121]–[124], and antibodies against the B31 Arp protein cause resolution of B. burgdorferi induced arthritis in mice [125]–[127]. N40 does not carry a plasmid with an lp28-1 PFam32 gene, and the JD1 and 297 lp28-1 plasmids are very similar to each other (99.5% identical over the nearly 15 Kbp), but are quite different from B31 lp28-1. These two lp28-1 types only have the partition genes and vls/vlsE region in common (Figures 5 and S2I). Between these two regions of the JD1 and 297 plasmids lies about 2.6 Kbp of DNA that contains a PFam106 gene (jd1_f23 and 297_f25) that is homologous to B31 lp38 genes b31_j23 and b31_j24. This JD1 protein is only about 40% identical to B31_J23 protein. At their left ends JD1 and 297 lp28-1s have about 6 Kbp that is about 99% identical to the right end extension of the B31 chromosome (above) and which contains an apparently intact PFam138 gene (b31_0852 in B31) and about 2.7 Kbp that has no ortholog in B31 and no convincing intact genes. The arp gene is not present on lp28-1 in the three new genomes discussed here. In N40 it is near the right end of lp28-5 (gene n40_y16), and in JD1 it is near the left end of lp28-4 (jd1_i37; and perhaps also in 297, although the sequence of the parallel region of its lp28-4 was not determined). The B31 and N40 Arp proteins are identical, and the JD1 homolog is 99.1% identical to them, so this movement of the arp gene among these different plasmids happened quite recently.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. sherwood.casjens@path.utah.edu

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.

Show MeSH
Related in: MedlinePlus