Evolutionary genomics of Borrelia burgdorferi sensu lato: findings, hypotheses, and the rise of hybrids.

Borrelia burgdorferi sensu lato (B. burgdorferi s.l.), the group of bacterial species represented by Lyme disease pathogens, has one of the most complex and variable genomic architectures among prokaryotes. Showing frequent recombination within and limited gene flow among geographic populations, the B. burgdorferi s.l. genomes provide an excellent window into the processes of bacterial evolution at both within- and between-population levels. Comparative analyses of B. burgdorferi s.l. genomes revealed a highly dynamic plasmid composition but a conservative gene repertoire. Gene duplication and loss as well as sequence variations at loci encoding surface-localized lipoproteins (e.g., the PF54 genes) are strongly associated with adaptive differences between species. There are a great many conserved intergenic spacer sequences that are candidates for cis-regulatory elements and non-coding RNAs. Recombination among coexisting strains occurs at a rate approximately three times the mutation rate. The coexistence of a large number of genomic groups within local B. burgdorferi s.l. populations may be driven by immune-mediated diversifying selection targeting major antigen loci as well as by adaptation to multiple host species. Questions remain regarding the ecological causes (e.g., climate change, host movements, or new adaptations) of the ongoing range expansion of B. burgdorferi s.l. and on the genomic variations associated with its ecological and clinical variability. Anticipating an explosive growth of the number of B. burgdorferi s.l. genomes sampled from both within and among species, we propose genome-based methods to test adaptive mechanisms and to identify molecular bases of phenotypic variations. Genome sequencing is also necessary for monitoring a likely increase of genetic admixture of previously isolated species and populations in North America and elsewhere.