BMC Genomics Research article Intergenic regions of Borrelia plasmids contain phylogenetically conserved RNA secondary structure motifs Nicholas Delihas BioMed Central Open Access Address: Department of Molecular Genetics and Microbiology, School of Medicine, Suny, Stony Brook, NY 11794-5222, USA Email: Nicholas Delihas - nicholas.delihas@sunysb.edu Published: 6 March 2009 BMC Genomics 2009, 10:101 doi:10.1186/1471-2164-10-101 This article is available from: http://www.biomedcentral.com/1471-2164/10/101 Received: 4 September 2008 Accepted: 6 March 2009 © 2009 Delihas; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Borrelia species are unusual in that they contain a large number of linear and circular plasmids. Many of these plasmids have long intergenic regions. These regions have many fragmented genes, repeated sequences and appear to be in a state of flux, but they may serve as reservoirs for evolutionary change and/or maintain stable motifs such as small RNA genes. Results: In an in silico study, intergenic regions of Borrelia plasmids were scanned for phylogenetically conserved stem loop structures that may represent functional units at the RNA level. Five repeat sequences were found that could fold into stable RNA-type stem loop structures, three of which are closely linked to protein genes, one of which is a member of the Borrelia lipoprotein_1 super family genes and another is the complement regulator-acquiring surface protein_1 (CRASP-1) family. Modeled secondary structures of repeat sequences display numerous base-pair compensatory changes in stem regions, including C-G→A-U transversions when orthologous sequences are compared. Base-pair compensatory changes constitute strong evidence for phylogenetic conservation of secondary structure. Conclusion: Intergenic regions of Borrelia species carry evolutionarily stable RNA secondary structure motifs. Of major interest is that some motifs are associated with protein genes that show large sequence variability. The cell may conserve these RNA motifs whereas allow a large flux in amino acid sequence, possibly to create new virulence factors but with associated RNA motifs intact. Background Intergenic regions of bacterial chromosomes carry impor- tant functional units such as transposable elements [1]. Small regulatory RNA genes are also abundantly found in regions between protein coding genes [2-7]. In E. coli, many intergenic regions and non-coding strands of known genes are transcribed, resulting in a heterogeneous collection of RNA transcripts, many of which are <65 nt [8]. Bacterial intergenic chromosomal regions also carry numerous small repeat sequences that can fold into RNA- type secondary structures [9-12]. Some represent non- autonomous miniature inverted repeat transposable ele- ments (MITEs) [13,1]. Many are found immediately downstream of, or overlapping terminal codons [14-16] and may be regulatory units [14,15,17]. Small repeat ele- ments carry a variety of motifs at either the DNA, tran- scribed RNA or translated protein levels and they may be engines for evolutionary change [16,17]. Borrelia burgdorferi was first isolated and shown to be the etiologic agent of Lyme Disease in the early 1980s [18,19]. The chromosomes of Borrelia burgdorferi str. B31 and its Page 1 of 12 (page number not for citation purposes)