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 g ene family that is homologous to the bdr gene family of the Lyme disease sp irochetes (previously referred to as the rep + or ORF-E gene family). Here we demonstrate that bdr related genes are widely distributed among pathogen ic Borrelia species and exist as large, polymorphic, plasmid carried, gene families. Twenty distinct bdr alleles were identified in isolates of the re lapsing fever spirochete, B. hermsii, and were localized to linear plasmids . Cloning and sequence analyses demonstrate that the putative Bdr functiona l domains (i.e. the phosphorylation motifs and the transmembrane C-terminal domain) are conserved across the genus while other regions of these protei ns exhibit variability. An assessment of the evolutionary relationships amo ng all known Bdr protein sequences obtained from five pathogenic Borrelia s pecies revealed that there are distinct Bdr sub-families. The recognition o f distinct phyletic clusters serves as the basis of a revised and simplifie d nomenclature for the bdr proteins that can be applied genus wide. At the biological level the delineation of multiple bdr sub-families within isogen eic populations raises the possibility that there may be functional partiti oning among alleles. In summary, the distribution and conservation of the B dr proteins suggests that they are important in the biology/pathogenesis of the Borrelia at the genus wide level. (C) 2000 Academic Press.