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Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species

Jackson, Andrew P. and Berry, Andrew and Aslett, Martin and Allinson, Harriet C. and Burton, Peter and Vavrova-Anderson, Jana and Brown, Robert and Browne, Hilary and Corton, Nicola and Hauser, Heidi and Gamble, John and Gilderthorp, Ruth and Marcello, Lucio and McQuillan, Jacqueline and Otto, Thomas D. and Quail, Michael A. and Sanders, Mandy J. and van Tonder, Andries and Ginger, Michael and Field, Mark C. and Barry, J. David and Hertz-Fowler, Christiane and Berriman, Matthew (2012) Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. Proceedings of the National Academy of Sciences, 109 (9). pp. 3416-3421. ISSN 0027-8424

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Abstract

Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections.

Item Type: Article
Journal or Publication Title: Proceedings of the National Academy of Sciences
Subjects: Q Science > QR Microbiology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 56719
Deposited By: ep_importer_pure
Deposited On: 07 Aug 2012 15:06
Refereed?: Yes
Published?: Published
Last Modified: 09 Apr 2014 23:56
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/56719

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