Academic journal article Genetics

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

Academic journal article Genetics

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

Article excerpt

ABSTRACT 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.

GENETIC 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 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; Retchless and Lawrence 2010). A paradox thereby arises as to how distinct clonal groups may rise and be maintained in local bacterial populations in the absence of intrinsic gene-flow barriers akin to reproductive isolation between eukaryotic species. A widely held hypothesis is adaptive specialization, in which distinct genotypes coexisting within local bacterial populations are thought to represent ecologically differentiated subpopulations or "ecotypes" (Cohan 2002; Koeppel et al. 2008). In the ecotype model, though, natural selection needs to be persistent and strong enough to overcome the homogenizing effects of genetic exchange (Doolittle and Papke 2006; Fraser et al. 2007; Lawrence and Retchless 2010). Frequencydependent selection (FDS) is a form of balancing selection capable of maintaining genetic diversity at an antigenic locus in a pathogen without the assumption of differentially adapted alleles (Levin 1988; Takahata and Nei 1990; Wiener 1996). To date, however, genome-wide consequences of FDS are largely unknown and FDS as a possible common cause of sympatric genome diversity in bacteria has not received nearly as much attention as the ecotype model.

Here we use comparative population genomics and computer simulation to understand the origin and maintenance of high local genomic diversity in natural populations of Borrelia burgdorferi sensu lato ("B. …

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