Molecular and evolutionary analysis of Borrelia burgdorferi 297 circular plasmid-encoded lipoproteins with OspE- and OspF-like leader peptides

We previously described two OspE and three OspF homologs in Borrelia burgdo rferi 297 (D. R. Akins, S. F. Porcella, T. G. Popova, D. Shevchenko, S. I. Baker, M. Li, M. V. Norgard, and J. D. Radolf, Mol. Microbiol. 18:507-520, 1995; D, R, Akins, K. W, Bourell, M. J. Caimano, M. V. Norgard, and J. D. R adolf, J. Clin. Investig. 101:2240-2250, 1998). In this study, we character ized four additional lipoproteins with OspE/F-like leader peptides (Elps) a nd demonstrated that all are encoded on plasmids homologous to cp32 and cp1 8 from the B31 and N40 strains, respectively. Statistical analysis of seque nce similarities using the binary comparison algorithm revealed that the ni ne lipoproteins from strain 297, as well as the OspE, OspF, and Erp protein s from the N40 and B31 strains, fall into three distinct families. Based up on the observation that these lipoproteins all contain highly conserved lea der peptides, we now propose that the ancestors of each! of the three famil ies arose from gene fusion events which joined a common N terminus to unrel ated proteins. Additionally, further sequence analysis of the strain 297 ci rcular plasmids revealed that rearrangements appear to have played an impor tant role in generating sequence diversity among the members of these three families and that recombinational events in the downstream flanking region s appear to have occurred independently of those within the lipoprotein-enc oding genes. The association of hypervariable regions with genes which are differentially expressed and/or subject to immunological pressures suggests that the Lyme disease spirochete has exploited recombinatorial processes t o foster its parasitic strategy and enhance its immunoevasiveness.