The availability of multiple genomes of closely related pathogen strains makes it possible to identify genome-wide variations associated with strain-specific phenotypes such as pathogenicity and virulence. One main challenge of gene-trait associative mapping in bacterial species is finding a way to minimize the effect of linkage among loci due to pervasive clonal population structures. A second concern is to distinguish selective sequence variations from random, selectively neutral differences among strains. Here we identified adaptive, strain-specific nucleotide polymorphisms (SSNPs) on the core genome of Borrelia burgdorferi, the Lyme disease pathogen. We minimized the linkage effect by comparing the genomes of seven isolates representing four genospecies (B. burgdorferi sensu stricto, B. bissettii, B. afzelii, and B. garinii) and four clonal groups of a single species (A, C, E, and K clones of B. burgdorferi sensu stricto). Identification of selective nucleotide polymorphisms was achieved by applying codon-based, tests of positive selection based on rates of synonymous ( KS) and nonsynonymous (KA) substitutions. We then tested for the presence of positive selection at 824 gene loci on the main chromosome, 68 loci on the linear plasmid lp54, and 26 loci on the circular plasmid cp26. Consequently, we identified 28 genes under positive selection without regard for lineage, 12 genes associated with genospecies divergence, and 7 genes associated with the adaptive divergence of B31, a highly invasive strain. We checked results by excluding loci with high alignment uncertainties, mapping positively selected sites on protein structure models, and evaluating the possibility of false positives. Cell envelope genes are significantly over-represented among the positively selected genes. Additional categories of interest are DNA metabolism, transcription, cell division, and regulation. Focused analyses on copy number variation of established immune elicitors and a survey of intraspecific recombination support a prominent role for adaptive evolution in the maintenance of the B. burgdorferi pathogen cycle. These findings highlight immune escape as a driver of positive natural selection via surface protein variation and possibly pathogen replication dynamics.
|Commitee:||Boissinot, Stephane, Lahti, David, Ostfeld, Richard, Singh, Shaneen|
|School:||City University of New York|
|School Location:||United States -- New York|
|Source:||DAI-B 72/05, Dissertation Abstracts International|
|Subjects:||Evolution and Development, Bioinformatics|
|Keywords:||Adaptive evolution, Borrelia burgdorferi, Hematogenous dissemination, Recombination, Relaxed selection, Single stage genes, Virulence|
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