A Population Genetic Study of Borrelia burgdorferi Sensu Stricto from Eastern Long Island, New York, Suggested Frequency-Dependent Selection, Gene Flow and Host Adaptation

Abstract

Eastern Long Island, New York, is one of the major foci of Lyme disease in the United States. As in almost all other parts of North America, Lyme disease in this region is caused by a single genomic species of spirochete, Borrelia burgdorferi sensu stricto. For three consecutive years, natural populations of Lyme Borrelia in this region were sampled and studied for gene flow among different locations, changes in population structure over time, and selective forces. The genetic diversity of Borrelia populations was measured at the outer surface protein A (ospA) locus using Cold Single-Stranded Conformation Polymorphism (Cold SSCP) analysis. The Borrelia populations were found to be highly polymorphic within any of thirteen local populations. Ewens-Watterson tests of neutrality revealed that the high level of genetic diversity within local Borrelia populations is maintained by balancing selection. Frequency-dependent selection for the different strains distinguished by the ospA alleles is likely the mechanism of the balancing selection. Allele frequency distributions of Borrelia populations were homogeneous across the region in any particular year, although different infection rates of local tick (Ixodes scapularis) populations suggested that the Borrelia populations were at least partially isolated. Since the allele frequency distribution changed over time, while remaining homogeneous over space, the nearly uniform allele frequency distribution across the region cannot be explained by recent geographic expansion from a single population. This uniform distribution across the region thus may be maintained by selection, or by a significant amount of migration or both. The genetic structure of B. burgdorferi sensu stricto also differed between spirochetes infecting nymphal ticks and those infecting adult ticks. Since larval and nymphal ticks have distinctly different host feeding preferences, host adaptation of spirochete populations is implied. This distinction and an animal study using chipmunks suggest that ticks infected by Borrelia as larvae may have high mortality in the wild. This study represents a genetic analysis of local populations of a bacterial species.

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

“…First, as a direct consequence of this balanced genome genealogy allele frequencies at all genomic loci tend to be evenly distributed (Figure 4). Indeed, allele frequency distributions in natural populations of B. burgdorferi s.s. are more even than expected from neutral evolution (Qiu et al 1997(Qiu et al , 2002Rannala et al 2000). Second, a genome genealogy with long internal and short terminal branches results in a clustering of genomic sequences into distinct groups, with large sequence differences between the groups and sequence homogeneity within the groups (Figure 7).…”

“…remain unclear. Initial surveys of genetic diversity at loci under strong immune-escape selection revealed evenly distributed allele frequencies consistent with frequency-dependent selection (Qiu et al 1997(Qiu et al , 2002). An alternative, although not necessarily mutually exclusive, hypothesis is that distinct clonal groups are maintained by host specialization Dykhuizen 2004, 2006).…”

Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe

“…Of the 16 ospC types found among isolates from various locations in Europe, including Slovenia, Austria, Switzerland, Germany, France and Denmark, 8 were identified in ticks collected from a 15 000 m 2 area of forest in southern Sweden. Table 3 shows how the nine multi-locus types would likely be classified by other typing systems: three based on single-strand conformation polymorphisms or reverse line-blotting of ospA or ospC (Lagal et al, 2003;Qiu et al, 1997Qiu et al, , 2002, and one based on RFLPs of the rrs-rrlA IGS (Liveris et al, 1995). Each of the nine multi-locus types of B. burgdorferi corresponded with a different ospC group of Wang et al (1999) and Seinost et al (1999a).…”

“…In fact, studies to date of strain diversity indicate that each Borrelia species comprises a variety of strains under what appears to be balancing selection (Dykhuizen et al, 1993;Mathiesen et al, 1997;Qiu et al, 1997). The presence of multiple strains has been suggested by studies of different genetic loci, both chromosomal and plasmid.…”

“…The presence of multiple strains has been suggested by studies of different genetic loci, both chromosomal and plasmid. Loci that have been studied include the chromosomal intergenic spacer (IGS) between the single 16S (rrs) rRNA and the first of two 23S (rrlA) rRNA genes (Liveris et al, 1995); the spacer between a 5S (rrf ) and the second 23S (rrlB) rRNA gene (Lee et al, 2000;Postic et al, 1994); ospA, a plasmidborne gene for an outer membrane lipoprotein Norris et al, 1999;Qiu et al, 1997;Wilske et al, 1993); ospC, a plasmid-borne gene for another outer membrane lipoprotein (Lagal et al, 2003;Livey et al, 1995;Theisen et al, 1995;Wang et al, 1999;Wilske et al, 1995); p66, a chromosomal gene for an integral outermembrane protein (Bunikis et al, 1998;Norris et al, 1997); and variable-number tandem repeat (VNTR) loci on both the chromosome and the plasmids (Farlow et al, 2002).…”