Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation

Emmanuel F Mongodin,Sherwood R Casjens,Wei-Gang Qiu,David R Riley,Levy C Vargas,Steven E Schutzer,Benjamin J Luft,Elliott Drabek,John F Bruno,Yozen A Hernandez,Brandi L Cantarel,John J Dunn,Yun Xu,Pedro E Pagan,Claire M Fraser

doi:10.1186/1471-2164-14-693

Abstract

BackgroundLyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. “bavariensis” (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. “finlandensis” (1).ResultsRobust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases.ConclusionsIntra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues.

Highlights

Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex
Because of recent dramatic reductions in the DNA sequencing costs, comparative genomics studies of Borrelia species are a cost effective way to provide a firm foundation for the generation of new, informed, and testable hypotheses which would be difficult or impossible to formulate by other means
In order to choose a panel of isolates for genome sequencing that maximized the represented B. burgdorferi s.s. genetic diversity, we Multi-locus sequence typing (MLST)-typed 64 such isolates (Figure 1) that reside in different major groups based on rRNA IGS1 spacer sequence [35,38] and outer surface protein C gene (ospC) sequence [35,36] while attempting to include a variety of hosts and geographical regions

Summary

Introduction

Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. Lyme disease, caused by the spirochete bacteria Borrelia burgdorferi, has become the most common vector-borne disease in the United States and Europe [1]. The B. burgdorferi species complex [12], B. burgdorferi sensu lato (B. burgdorferi s.l.), is classified into different genomic groups or species (sometimes called “genospecies”) on the basis of their molecular phylogeny. The most common species in Europe are B. garinii [19], B. afzelii [20], B. burgdorferi s.s., B. valaisiana and B spielmanii [9,21]. We find that genotypes characterized as highly pathogenic in humans are the ones that have a broad host-species range, able to colonize both continents [34]

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Results

Conclusion