Evolutionary and molecular analyses of the Borrelia bdr super gene family: delineation of distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs.

B. turicatae, a causative agent of relapsing fever, carries a polymorphic gene family that is homologous to the bdr gene family of the Lyme disease spirochetes (previously referred to as the rep+ or ORF-E gene family). Here we demonstrate that bdr related genes are widely distributed among pathogenic Borrelia species and exist as large, polymorphic, plasmid carried, gene families. Twenty distinct bdr alleles were identified in isolates of the relapsing fever spirochete, B. hermsii, and were localized to linear plasmids. Cloning and sequence analyses demonstrate that the putative Bdr functional domains (i.e. the phosphorylation motifs and the transmembrane C-terminal domain) are conserved across the genus while other regions of these proteins exhibit variability. An assessment of the evolutionary relationships among all known Bdr protein sequences obtained from five pathogenic Borrelia species revealed that there are distinct Bdr sub-families. The recognition of distinct phyletic clusters serves as the basis of a revised and simplified nomenclature for the bdr proteins that can be applied genus wide. At the biological level the delineation of multiple bdr sub-families within isogeneic populations raises the possibility that there may be functional partitioning among alleles. In summary, the distribution and conservation of the Bdr proteins suggests that they are important in the biology/pathogenesis of the Borrelia at the genus wide level.