Article

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

Department of Biology, The Graduate Center, City University of New York, New York, New York 10016, USA.
Genetics (Impact Factor: 5.96). 09/2011; 189(3):951-66. DOI: 10.1534/genetics.111.130773
Source: PubMed

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.

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    • "The mechanism by which ospC diversity is maintained is also debated and mixed theoretical and empirical evidence exists as to whether each host species transmits a consistent subset of genotypes , a prerequisite for the maintenance of ospC diversity by MNP (Anderson and Norris, 2006; Brisson and Dykhuizen, 2004; Hanincova et al., 2006; Vuong et al., 2013). Furthermore, even if certain hosts transmit a subset of genotypes at a higher frequency than others, whether any selection pressure exerted by host specialization can overcome other selective or non-selective forces and significantly influence genotype diversity in a community remains to be tested (Brisson et al., 2012; Haven et al., 2011; Kurtenbach et al., 2006). The dilution effect and MNP hypotheses jointly predict additive increases in human Lyme disease risk in species-poor, P. leucopusdominated , communities (Brisson and Dykhuizen, 2006). "

    Full-text · Dataset · Nov 2014
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    • "The mechanism by which ospC diversity is maintained is also debated and mixed theoretical and empirical evidence exists as to whether each host species transmits a consistent subset of genotypes , a prerequisite for the maintenance of ospC diversity by MNP (Anderson and Norris, 2006; Brisson and Dykhuizen, 2004; Hanincova et al., 2006; Vuong et al., 2013). Furthermore, even if certain hosts transmit a subset of genotypes at a higher frequency than others, whether any selection pressure exerted by host specialization can overcome other selective or non-selective forces and significantly influence genotype diversity in a community remains to be tested (Brisson et al., 2012; Haven et al., 2011; Kurtenbach et al., 2006). The dilution effect and MNP hypotheses jointly predict additive increases in human Lyme disease risk in species-poor, P. leucopusdominated , communities (Brisson and Dykhuizen, 2006). "
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    ABSTRACT: The effect of biodiversity declines on human health are currently debated, but empirical assessments are lacking. Lyme disease provides a model system to assess relationships between biodiversity and human disease because the etiologic agent, Borrelia burgdorferi, is transmitted in the United States by the generalist black-legged tick (Ixodes scapularis) among a wide range of mammalian and avian hosts. The 'dilution effect' hypothesis predicts that species-poor host communities dominated by white-footed mice (Peromyscus leucopus) will pose the greatest human risk because P. leucopus infects the largest numbers of ticks, resulting in higher human exposure to infected I. scapularis ticks. P. leucopus-dominated communities are also expected to maintain a higher frequency of those B. burgdorferi outer surface protein C (ospC) genotypes that this host species more efficiently transmits ('multiple niche polymorphism' hypothesis). Because some of these genotypes are human invasive, an additive increase in human disease risk is expected in species-poor settings. We assessed these theoretical predictions by comparing I. scapularis nymphal infection prevalence, density of infected nymphs and B. burgdorferi genotype diversity at sites on Block Island, RI, where P. leucopus dominates the mammalian host community, to species-diverse sites in northeastern Connecticut. We found no support for the dilution effect hypothesis; B. burgdorferi nymphal infection prevalence was similar between island and mainland and the density of B. burgdorferi infected nymphs was higher on the mainland, contrary to what is predicted by the dilution effect hypothesis. Evidence for the multiple niche polymorphism hypothesis was mixed: there was lower ospC genotype diversity at island than mainland sites, but no overrepresentation of genotypes with higher fitness in P. leucopus or that are more invasive in humans. We conclude that other mechanisms explain similar nymphal infection prevalence in both communities and that high ospC genotype diversity can be maintained in both species-poor and species-rich communities.
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    • "Selective survival of B. burgdorferi sl in the tick midgut, depending on the source of serum and the genetic background of the bacteria, can manifest itself in the selective replacement of Borrelia strains during the tick life cycle [36]. The high diversity of local spirochete populations has often been connected to host specialization or to the coexistence of multiple genospecies in the region with pervasive recombination among sympatric genomes [11,47]. Multiple-niche polymorphism, a form of balancing selection, can maintain diversity within the population [44]. "
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