Suggested Role for G4 DNA in Recombinational Switching at the Antigenic Variation Locus of the Lyme Disease Spirochete

2013-03-01T12:48:03Z (GMT) by Rupali Walia George Chaconas
<div><p>Antigenic variation through targeted DNA rearrangements provides a powerful diversity generating mechanism that allows a variety of pathogens to stay one step ahead of acquired immunity in their hosts. The Lyme disease spirochete encodes such a system that is required for persistent infection. The <i>vls</i> locus, carried on a 29 kb linear plasmid (lp28-1) in the type strain B31, carries 15 silent cassettes from which information is unidirectionally transferred into the expression locus, <i>vlsE.</i> Recent studies have surprisingly shown that, with the exception of the RuvAB branch migrase, no other known recombination/repair proteins appear to play a role in the recombinational switching process. In the work presented here we show that G4 DNA can be formed by sequences within the B31 <i>vlsE</i> locus, prompting us to investigate the presence of potential G4-forming DNA throughout the <i>vls</i> locus of several Lyme spirochete strains and species. We found that runs of G, three nucleotides and longer occur at a very high density, with a greater than 100-fold strand-specific distribution in the <i>vls</i> locus of three <i>B. burgdorferi</i> strains as well as in <i>B. afzelii and B. garinii,</i> in spite of the bias for the use of A-T rich codons in <i>Borrelia</i> species. Our findings suggest the possibility that G4 DNA may be a mediator of recombinational switching at the <i>vlsE</i> locus in the Lyme spirochetes.</p> </div>