Schematic diagram of the vls system structure and recombination pattern. (A) In the B. burgdorferi of B31‐type strain, the vls locus is located on lp28‐1 and the vlsE gene is located near the telomere of the hairpin, 15 silent cassettes are located near and upstream of vlsE, but in the opposite direction (arrow). (B) The vlsE region is described in more detail. It is composed of the variable region (VR) and the constant region (CR), the variable region is flanked by 17‐bp direct repeats (DRs). To the left of vlsE is a part of the promoter (P), with the −10 and −35 inverted repeat sequences (about 100‐bp in length). (C) The central variable cassette region of vlsE is comprised of six variable regions (VR1–VR6) and six invariant regions (IRs). (D) In infected mammalian hosts, a random, unidirectional, and segmental combination of the vlsE protein‐coding site and the silent cassettes leads to differences in the expression of vlsE variants. Modified from Ref 16, 19, 30