Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
| العنوان: | Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species |
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| المؤلفون: | Michael L. Ginger, Andrew Berry, Christiane Hertz-Fowler, Michael A. Quail, Andrew P. Jackson, Mark C. Field, Harriet C. Allison, Thomas D. Otto, Nicola Corton, Jana Vavrova-Anderson, Heidi Hauser, J. David Barry, Robert W. Brown, Jacqueline A. McQuillan, Peter Burton, Ruth Gilderthorp, Mandy Sanders, Andries J. van Tonder, Hilary P. Browne, Lucio Marcello, John Gamble, Martin Aslett, Matthew Berriman |
| المصدر: | Proceedings of the National Academy of Sciences. 109:3416-3421 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Models, Molecular, Protein Conformation, Trypanosoma congolense, Molecular Sequence Data, Trypanosoma brucei brucei, 030231 tropical medicine, Protozoan Proteins, Trypanosoma brucei, Evolution, Molecular, 03 medical and health sciences, Antigenic Diversity, 0302 clinical medicine, Species Specificity, Phylogenetics, parasitic diseases, Antigenic variation, medicine, Animals, Humans, African trypanosomiasis, Amino Acid Sequence, Trypanosoma vivax, Phylogeny, Immune Evasion, 030304 developmental biology, Recombination, Genetic, Genetics, 0303 health sciences, Multidisciplinary, Base Sequence, Sequence Homology, Amino Acid, biology, Phylogenetic tree, DNA, Protozoan, Biological Sciences, biology.organism_classification, medicine.disease, Antigenic Variation, QR, 3. Good health, Trypanosoma, Genome, Protozoan, Sequence Alignment, Variant Surface Glycoproteins, Trypanosoma |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1117313109 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::90c6367e0f99367927ad86e08239e99b https://doi.org/10.1073/pnas.1117313109 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....90c6367e0f99367927ad86e08239e99b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.1117313109 |