ArticleProceedings of the National Academy of Sciences of the United States of America2012
Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 157 citations in OpenAlex.
- De Novo Assembly of the Trypanosoma congolense Genome Reveals an Organization Influenced by Antigenic Variation but Distinct from Trypanosoma brucei.Genome biology and evolution · 2026Article
- Trypanosoma vivax elicits both Th1 and Th2 immunological responses in experimentally infected cattle.PloS one · 2025Article
- Why the Jenner/Pasteur paradigm is insufficient for controlling vector-borne diseases and the role of microbiota-mediated interactions.Current research in parasitology & vector-borne diseases · 2025Review
- Insights into the evolution, virulence and speciation ofEmerging microbes & infections · 2024Article
- Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.Genome research · 2024Article
- Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2.International journal of molecular sciences · 2024Review
- Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.Virulence · 2023Review
- Molecular identification ofFrontiers in veterinary science · 2023Article
- Vivaxin genes encode highly immunogenic, non-variant antigens on the Trypanosoma vivax cell-surface.PLoS neglected tropical diseases · 2022Article
- Transcriptomic profiling of Trypanosoma congolense mouthpart parasites from naturally infected flies.Parasites & vectors · 2022Article
- An Update on African Trypanocide Pharmaceutics and Resistance.Frontiers in veterinary science · 2022Review
- Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.Frontiers in cellular and infection microbiology · 2022Review
- Genomics of Trypanosomatidae: Where We Stand and What Needs to Be Done?Pathogens (Basel, Switzerland) · 2021Review
- Identification of a novel variant erythrocyte surface antigen-1 (VESA1) in Babesia orientalis.Parasitology research · 2021Article
- Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Article
- Reliable, scalable functional genetics in bloodstream-form Trypanosoma congolense in vitro and in vivo.PLoS pathogens · 2021Article
- Variant antigen diversity in Trypanosoma vivax is not driven by recombination.Nature communications · 2020Article
- Escaping the immune system by DNA repair and recombination in African trypanosomes.Open biology · 2019Review
27 more citing papers are in PubMed but not listed here.
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23 authors at 5 institutions in 1 country.
Funding
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.
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