Insights into Mechanisms of Bacterial Antigenic Variation Derived from the Complete Genome Sequence of Anaplasma marginale

: Persistence of Anaplasma spp. in the animal reservoir host is required for efficient tick‐borne transmission of these pathogens to animals and humans. Using A. marginale infection of its natural reservoir host as a model, persistent infection has been shown to reflect sequential cycles in which antigenic variants emerge, replicate, and are controlled by the immune system. Variation in the immunodominant outer‐membrane protein MSP2 is generated by a process of gene conversion, in which unique hypervariable region sequences (HVRs) located in pseudogenes are recombined into a single operon‐linked msp2 expression site. Although organisms expressing whole HVRs derived from pseudogenes emerge early in infection, long‐term persistent infection is dependent on the generation of complex mosaics in which segments from different HVRs recombine into the expression site. The resulting combinatorial diversity generates the number of variants both predicted and shown to emerge during persistence.