AUTHOR=Norris Steven J. , Brangulis Kalvis 

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

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1469411

DOI=10.3389/fmicb.2024.1469411

ISSN=1664-302X

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