Journal Article

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

Ginger, Michael L, Marcello, Lucio, Sanders, Mandy J, Hertz-Fowler, Christiane, Brown, Robert, Quail, Michael A, Burton, Peter, Gilderthorp, Ruth, Field, Mark C, Jackson, Andrew P, Vavrova-Anderson, Jana, Berriman, Matthew, Berry, Andrew, Allison, Harriet C, Gamble, John, Aslett, Martin, Otto, Thomas D, van Tonder, Andries, McQuillan, Jacqueline, Barry, J. David, Browne, Hilary, Corton, Nicola, Hauser, Heidi

2012

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: African trypanosomiasis / Amino Acid Sequence / Animals / Antigenic variation / Antigenic Variation - genetics / Antigens / Base Sequence / Biological Sciences / Biological variation / blood / Blood parasites / Cell surface / Charge transfer devices / Chronic infection / DNA, Protozoan - genetics / Evolution / Evolution, Molecular / Evolutionary biology / genes / Genome, Protozoan / Genomes / Glycoproteins / Humans / Immune Evasion - genetics / Immune response / interspecific variation / Models, Molecular / Molecular Sequence Data / Parasites / Parasitism / Pathogens / Phylogenetics / Phylogeny / Protein Conformation / Protozoan Proteins - chemistry / Protozoan Proteins - genetics / Recombination / Recombination, Genetic / Sequence Alignment / Sequence Homology, Amino Acid / species differences / Species Specificity / surface proteins / Trypanosoma brucei / Trypanosoma brucei brucei - genetics / Trypanosoma brucei brucei - immunology / Trypanosoma congolense / Trypanosoma congolense - genetics / Trypanosoma congolense - immunology / Trypanosoma vivax / Trypanosoma vivax - genetics / Trypanosoma vivax - immunology / Trypanosome / variant surface glycoprotein / variant surface glycoproteins / Variant Surface Glycoproteins, Trypanosoma - chemistry / Variant Surface Glycoproteins, Trypanosoma - genetics / Variant Surface Glycoproteins, Trypanosoma - immunology / Vector-borne diseases