Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

Casjens, Sherwood; Mongodin, Emmanuel F.; Qiu, Wei; Dunn, John J.; Luft, Benjamin J.; Fraser, Claire M.; Schutzer, Steve E.

doi:10.1128/jb.05951-11

Cited by 64 publications

(51 citation statements)

References 12 publications

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“…genomes and focused on the comparison of 14 conspecific genomes of the genospecies B. burgdorferi sensu stricto (B. burgdorferi s.s.) (Table 1) (Fraser et al 1997;Casjens et al 2000Casjens et al , 2011aCasjens et al , 2011bGlockner et al 2004Glockner et al , 2006Schutzer et al 2011). Ten of the B. burgdorferi s.s. genomes were from sympatric isolates from the northeastern United States (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of .13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. We suggest that pervasive recombination makes it less likely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in the northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and human virulence. G ENETIC discontinuity, the basis of biodiversity, is ubiquitous in prokaryotes as well as in eukaryotes. Most bacterial populations display a highly clonal genetic structure, in which the observable number of multilocus genotypes is far fewer than the number expected under the assumption of free recombination (Maynard Smith et al. 1993). Bacterial clonality was originally thought of as a result of a lack or rarity of recombination among asexually reproducing and independently evolving clones (Ochman and Selander 1984). Since then, molecular surveys of natural bacterial populations using protein electrophoresis, multilocus sequencing typing (MLST), and whole-genome PRJNA3, PRJNA28633, PRJNA19839, PRJNA29359, PRJNA28629, PRJNA29357, PRJNA21003, PRJNA19835, PRJNA28627, PRJNA21001, PRJNA29361, PRJNA28621, PRJNA19837, PRJNA20999, PRJNA28631, PRJNA29363, PRJNA17057, PRJNA19841, PRJNA12554, PRJNA28625, PRJNA29573, PRJNA19843, and PRJNA28635. 1 Present address: Odum School of Ecology, University of Georgia, Athens, GA 30602. sequencing revealed that horizontal genetic exchange is in fact often more frequent than point mutations in bacteria, including species known as strongly clonal (Maynard Smith et al. 1993;Feil and Spratt 2001;Didelot and Maiden 2010;Retc...

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Section: Methodsmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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“…Compared to LD Borrelia species, for which genome sequences are available for 20 or more strains among 5 species (20)(21)(22)(23), less is known about the genomes of RF Borrelia species. Reportedly complete chromosome and plasmid sequences are available for only three Old World species: B. duttonii, B. recurrentis, and B. crocidurae (24,25).…”

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confidence: 99%

Large Linear Plasmids of Borrelia Species That Cause Relapsing Fever

et al. 2013

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c Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of ϳ160 kb, or ϳ10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central ϳ25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids.

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“…The chromosomes, ranging in size from 904 kb to 932 kb, exhibit a high degree of synteny in terms of both gene content and order. (Three of the chromosomes in the report by Casjens et al [5] were not closed and thus are not complete.) The linear plasmids, like the chromosome, have hairpin telomeres that are recognized by the telomere resolvase ResT, which cleaves the circular dimer resulting from replication into two linear daughter molecules (6).…”

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confidence: 84%

“…Much can be learned from continued analysis and experimentation using the wealth of genome sequence information generated by Casjens et al (5), as well as by other groups that have sequenced the genomes of other borreliae. Future studies will likely include (i) comparison of metabolic pathways, nutrient transport systems, DNA recombination and repair, and other mechanisms potentially crucial to the organisms' survival and growth in different host species; (ii) identification of the important conserved proteins and domains involved in adherence, antigenic variation, and other activities critical to colonization, dissemination, inflammatory reactions and immune evasion; (iii) clarification of the roles of the multiple paralogous families present in the plasmids in pathogenesis; and (iv) the characterization of cis-and trans-acting elements involved in the elaborate gene regulation that is essential in the transition between vertebrate and arthropod environments.…”

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confidence: 99%