{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T10:39:00Z","timestamp":1778323140588,"version":"3.51.4"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>VMP-like sequence (<jats:italic>vls<\/jats:italic>) antigenic variation systems are present in every Lyme disease <jats:italic>Borrelia<\/jats:italic> strain with complete genome sequences. The linear plasmid-encoded <jats:italic>vls<\/jats:italic> system consists of a single expression site (<jats:italic>vlsE<\/jats:italic>) and contiguous array(s) of silent cassettes that have ~90% identity with the central cassette region of the cognate <jats:italic>vlsE<\/jats:italic> gene; antigenic variation occurs through random, segmental, and unidirectional recombination of <jats:italic>vls<\/jats:italic> silent cassette sequences into the <jats:italic>vlsE<\/jats:italic> expression site. Automated annotation programs do not accurately recognize <jats:italic>vls<\/jats:italic> silent cassette sequences, so these regions are not correctly annotated in most genomic sequences. In this study, the <jats:italic>vls<\/jats:italic> sequences were re-analyzed in the genomic sequences of 31 available Lyme disease <jats:italic>Borrelia<\/jats:italic> and one relapsing fever <jats:italic>Borrelia<\/jats:italic> organisms, and this information was utilized to systematically compare the <jats:italic>vls<\/jats:italic> systems in different species and strains. In general, the results confirm the conservation of the overall architecture of the <jats:italic>vls<\/jats:italic> system, such as the head-to-head arrangement of <jats:italic>vlsE<\/jats:italic> and a contiguous series of <jats:italic>vlsS<\/jats: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 <jats:italic>vls<\/jats:italic> silent cassette arrays through point mutations, short indels, duplication events, and rearrangements. The probable occurrence of convergent evolution toward a <jats:italic>vls<\/jats:italic> system-like locus is exemplified by <jats:italic>Borrelia turcica<\/jats:italic>, a variable large protein (Vlp) expressing organism that is a member of the relapsing fever <jats:italic>Borrelia<\/jats:italic> group.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1469411","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T04:45:07Z","timestamp":1728535507000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Meta-analysis of the Vmp-like sequences of Lyme disease Borrelia: evidence for the evolution of an elaborate antigenic variation system"],"prefix":"10.3389","volume":"15","author":[{"given":"Steven J.","family":"Norris","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalvis","family":"Brangulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s10482-014-0164-x","article-title":"A phylogenomic and molecular marker based proposal for the division of the genus Borrelia into two genera: the emended genus Borrelia containing only the members of the relapsing fever Borrelia, and the genus Borreliella gen. 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