Jackson, A.P. et al. (2012) Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. Proceedings of the National Academy of Sciences of the United States of America, 109(9), pp. 3416-3421. (doi: 10.1073/pnas.1117313109)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.1117313109
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: | Articles (Other) |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Marcello, Dr Lucio and Anderson, Dr Jana and Barry, Professor J |
| Authors: | Jackson, A.P., Berry, A., Aslett, M., Allison, H.C., Burton, P., Vavrova-Anderson, J., Brown, R., Browne, H., Corton, N., Hauser, H., Gamble, J., Gilderthorp, R., Marcello, L., McQuillan, J., Otto, T.D., Quail, M.A., Sanders, M.J., van Tonder, A., Ginger, M.L., Field, M.C., Barry, J.D., Hertz-Fowler, C., and Berriman, M. |
| Subjects: | Q Science > QR Microbiology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Journal Abbr.: | PNAS |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 13 February 2012 |
| Copyright Holders: | Copyright © 2012 National Academy of Sciences |
| First Published: | First published in Proceedings of the National Academy of Sciences |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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