Meta-analysis of the Vmp-like sequences of Lyme disease : evidence for the evolution of an elaborate antigenic variation system.

VMP-like sequence () antigenic variation systems are present in every Lyme disease strain with complete genome sequences. The linear plasmid-encoded system consists of a single expression site () and contiguous array(s) of silent cassettes that have ~90% identity with the central cassette region of the cognate gene; antigenic variation occurs through random, segmental, and unidirectional recombination of silent cassette sequences into the expression site. Automated annotation programs do not accurately recognize silent cassette sequences, so these regions are not correctly annotated in most genomic sequences. In this study, the sequences were re-analyzed in the genomic sequences of 31 available Lyme disease and one relapsing fever organisms, and this information was utilized to systematically compare the systems in different species and strains. In general, the results confirm the conservation of the overall architecture of the system, such as the head-to-head arrangement of and a contiguous series of silent cassette sequences and presence of inverted repeat sequences between the two regions. However, the data also provide evidence for the divergence of the silent cassette arrays through point mutations, short indels, duplication events, and rearrangements. The probable occurrence of convergent evolution toward a system-like locus is exemplified by , a variable large protein (Vlp) expressing organism that is a member of the relapsing fever group.