Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?

Devlin, R., Marques, C. A. and McCulloch, R. (2017) Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome? Current Genetics, 63(3), pp. 441-449. (doi: 10.1007/s00294-016-0662-7) (PMID:27822899) (PMCID:PMC5422504)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:De Almeida Marques, Dr Catarina and McCulloch, Professor Richard
Authors: Devlin, R., Marques, C. A., and McCulloch, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Current Genetics
Publisher:Springer Berlin Heidelberg
ISSN (Online):1432-0983
Published Online:07 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Current Genetics 63(3):441-449
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
515891Chromosomal recombination and repair in African trypanosomesRichard McCullochWellcome Trust (WELLCOME)089172/Z/09/ZIII - PARASITOLOGY
558541Do DNA double strand breaks initiate antigenic variation by homologous recombination in Trypanossoma brucei?Richard McCullochWellcome Trust (WELLCOME)093589/Z/10/ZIII - PARASITOLOGY
606431Kinase dependent control of DNA replication and repair as a drug target in Trypanosoma brucei.Richard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/K006495/1III - PARASITOLOGY