title: Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.
abstract: A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG) coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom. james.hall@york.ac.uk
authors.forename: James P J
authors.initials: JP
authors.lastname: Hall
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wang
authors.forename: J David
authors.initials: JD
authors.lastname: Barry
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017125:Genes, Protozoan; D014644:Genetic Variation; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D011544:Pseudogenes; D016053:RNA, Protozoan / Q000097:blood / Q000378:metabolism; D013499:Surface Properties; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014352:Trypanosomiasis / Q000097:blood / Q000276:immunology / Q000469:parasitology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016053:RNA, Protozoan