title: Conservation of a gene conversion mechanism in two distantly related paralogues of Anaplasma marginale.
abstract: Anaplasmataceae, the causative agents of anaplasmosis and ehrlichiosis, persist in the bloodstream of their mammalian hosts, allowing acquisition and transmission by tick vectors. Anaplasma marginale establishes persistent infection characterized by sequential cycles of rickettsaemia in which new antigenic variants emerge. The two most immunodominant outer membrane proteins, MSP2 and MSP3, are paralogues, each encoded by a distinct family of related genes. This study demonstrates that, although the two gene families have diverged substantially, each has maintained a similar mechanism to generate structurally and antigenically polymorphic surface antigens. Like MSP2, MSP3 is expressed from a single locus in which variation of the expressed msp3 gene is generated by recombination using msp3 pseudogenes. Each of the msp3 pseudogenes encodes a unique central variable region (CVR) flanked by conserved 5' and 3' regions. Changes in the CVR of the expressed msp3, concomitant with invariance of the pseudogenes, indicate that expression site variation is generated using gene conversion. A. marginale thus maintains two large, separate systems within its small genome to generate antigenic variation of its surface proteins, while analogous structural elements indicate a common mechanism.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Florida, 2015 SW 16th Avenue, Gainesville, FL 32611-0880, USA. meeusp@mail.vetmed.ufl.edu
authors.forename: Patrick F M
authors.initials: PF
authors.lastname: Meeus
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Brayton
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Barbet
mesh_terms: D000208:Acute Disease; D000709:Anaplasma / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D000712:Anaplasmosis / Q000382:microbiology; D000818:Animals; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology*; D002908:Chronic Disease; D005785:Gene Conversion; D008969:Molecular Sequence Data; D011544:Pseudogenes; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C103346:major surface protein 3, Anaplasma marginale; C103348:msp2 protein, Anaplasma marginale