Evolution of Borrelia burgdorferi | CDC EID

EID Journal Home > Volume 16, Number 6–June 2010

Volume 16, Number 6–June 2010
Research
Evolution of Northeastern and Midwestern Borrelia burgdorferi, United States
Dustin Brisson, Mary F. Vandermause, Jennifer K. Meece, Kurt D. Reed, and Daniel E. Dykhuizen
Author affiliations: University of Pennsylvania, Philadelphia, Pennsylvania, USA (D. Brisson); Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA (M.F. Vandermause, J.K. Meece); Northwestern University/Feinberg School of Medicine, Chicago, Illinois, USA (K.D. Reed); and Stony Brook University, Stony Brook, New York, USA (D.E. Dykhuizen)

Suggested citation for this article

Abstract
The per capita incidence of human Lyme disease in the northeastern United States is more than twice that in the Midwest. However, the prevalence of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the tick vector is nearly identical in the 2 regions. The disparity in human Lyme disease incidence may result from a disparity in the human invasiveness of the bacteria in the Northeast and Midwest caused by fundamentally different evolutionary histories. B. burgdorferi populations in the Northeast and Midwest are geographically isolated, enabling evolutionary divergence in human invasiveness. However, we found that B. burgdorferi populations in the Northeast and Midwest shared a recent common ancestor, which suggests that substantial evolutionary divergence in human invasiveness has not occurred. We propose that differences in either animal ecology or human behavior are the root cause of the differences in human incidence between the 2 regions.
Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common vector-borne disease in the United States (1). B. burgdorferi is transmitted to humans during the blood meal of an infected Ixodes tick, predominantly Ixodes scapularis in North America (2). The prevalence and density of B. burgdorferi–infected I. scapularis ticks are nearly identical in the northeastern and midwestern United States, the regions with the highest incidence of Lyme disease in humans (3–6); however, the number of human Lyme disease cases reported in the Northeast and Midwest is not (1). The overwhelming majority of Lyme disease cases in the United States are reported from the Northeast (82%), followed distantly by the Midwest (9%) (1). Similarly, per capita Lyme disease incidence is >2× greater in the Northeast than the Midwest. We address the hypothesis that B. burgdorferi populations in the Northeast and Midwest have fundamentally different evolutionary histories, which may result in differing degrees of human invasiveness.

The evolutionary and demographic histories of B. burgdorferi in the Northeast have been intensively studied. The effective population size of northeastern B. burgdorferi is small because of its recent colonization of the northern United States and its life-history strategy (7,8). The strikingly impoverished neutral genetic diversity and high linkage disequilibrium within B. burgdorferi populations likely result from small effective population sizes (9–11). Genetic loci are found in perfect or near-perfect association in B. burgdorferi in the Northeast (9–12). Strong linkage disequilibrium among genetic loci can result from several evolutionary and ecologic forces in addition to small population size (drift), such as lack of recombination machinery or limited opportunity for gene exchange (13). Genetically diverse strains of B. burgdorferi often are found within the same tick or same vertebrate host, suggesting ample opportunity for genetic exchange (4,14). Evidence is strong that recombination occurs within a genomic lineage of B. burgdorferi (15–17). Thus, B. burgdorferi has the opportunity and the recombination system needed for genetic exchange. A historically small effective population size is a parsimonious explanation for the low neutral genetic diversity and strong linkage disequilibrium.

The evolutionary and demographic histories of B. burgdorferi in the Midwest are comparatively understudied. On the coarse scale, the evolutionary history and ecology of B. burgdorferi in the Northeast and Midwest appear similar. Both regions have oak-maple–dominated forests ideal for deer and the small mammals that maintain the I. scapularis and B. burgdorferi populations, were under the Pleistocene ice sheet, and were recently colonized by B. burgdorferi. The differences accounting for a lower Lyme disease incidence in the Midwest than the Northeast are not clear but most likely can be found on a finer scale in the evolutionary history of B. burgdorferi (this study), the tick vector (8), or human exposure.

The differences accounting for a lower Lyme disease incidence in the Midwest than the Northeast are not clear but are likely to be found on a finer evolutionary or ecologic scale. A recent report suggested that a lower proportion of the 16S–23S rRNA intergenic spacer (IGS) type 1 (RST-1) allele in midwestern B. burgdorferi populations, an allele associated with human invasiveness in the northeastern United States, may account for the differences in human Lyme disease incidence (8). However, the 16S–23S rRNA IGS does not directly influence B. burgdorferi invasiveness; it is in linkage disequilibrium with a gene of major effect in the Northeast. The linkage patterns in midwestern B. burgdorferi are as yet unstudied. A fundamentally different evolutionary history would result in divergent linkage disequilibrium patterns between the Northeast and the Midwest and potentially result in differing degrees of human invasiveness associated with alleles at the 16S–23S rRNA spacer.

For this study, we used a phylogenetic framework to analyze the evolutionary and demographic histories of B. burgdorferi in the midwestern and northeastern United States (18). A previous multilocus sequencing typing study of 4 B. burgdorferi loci (outer surface protein C [ospC], 16S–23S rRNA (rrs-rrl-A), ospA, and outer membrane protein [p66]) from strains isolated in the Northeast identified 9 distinct lineages with complete linkage among alleles at the 4 loci (10). That study analyzed statistical associations of haplotypes at each locus without regard to the underlying evolutionary relationships of sequences. In this study, we analyzed ospC, rrs-rrlA, ospB, and ospA (p66 contains little evolutionary information [10]) from midwestern and northeastern populations in a phylogenetic framework to investigate the shared and vicariant evolutionary and demographic histories of B. burgdorferi from geographically isolated regions.

open here to see the full-text:
Evolution of Borrelia burgdorferi | CDC EID