Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?
All pathogens must survive host immune attack and, amongst the survival strategies that have evolved, antigenic variation is a particularly widespread reaction to thwart adaptive immunity. Though the reactions that underlie antigenic variation are highly varied, recombination by gene conversion is a widespread approach to immune survival in bacterial and eukaryotic pathogens. In the African trypanosome, antigenic variation involves gene conversion-catalysed movement of a huge number of variant surface glycoprotein (VSG) genes into a few telomeric sites for VSG expression, amongst which only a single site is actively transcribed at one time. Genetic evidence indicates VSG gene conversion has co-opted the general genome maintenance reaction of homologous recombination, aligning the reaction strategy with targeted rearrangements found in many organisms. What is less clear is how gene conversion might be initiated within the locality of the VSG expression sites. Here, we discuss three emerging models for VSG switching initiation and ask how these compare with processes for adaptive genome change found in other organisms.
The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davis Building, 120 University Place, Glasgow, G12 8TA, UK.
Rebecca
R
Devlin
The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davis Building, 120 University Place, Glasgow, G12 8TA, UK.|Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, UK.
Catarina A
CA
Marques
The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davis Building, 120 University Place, Glasgow, G12 8TA, UK. Richard.mcculloch@glasgow.ac.uk.
Richard
http://orcid.org/0000-0001-5739-976X
R
McCulloch
D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D000940:Antigenic Variation / Q000235:genetics; D000941:Antigens / Q000032:analysis* / Q000276:immunology; D004261:DNA Replication / Q000235:genetics; D005785:Gene Conversion / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D057131:Immune Evasion / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D014347:Trypanosoma brucei gambiense / Q000235:genetics* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000235:genetics* / Q000276:immunology / Q000469:parasitology
D000941:Antigens
Antigenic variation; DNA repair; DNA replication; Trypanosome; Variant surface glycoprotein