title: Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom. andrew.jackson@sanger.ac.uk
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jackson
authors.forename: Andrew
authors.initials: A
authors.lastname: Berry
authors.forename: Martin
authors.initials: M
authors.lastname: Aslett
authors.forename: Harriet C
authors.initials: HC
authors.lastname: Allison
authors.forename: Peter
authors.initials: P
authors.lastname: Burton
authors.forename: Jana
authors.initials: J
authors.lastname: Vavrova-Anderson
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: Hilary
authors.initials: H
authors.lastname: Browne
authors.forename: Nicola
authors.initials: N
authors.lastname: Corton
authors.forename: Heidi
authors.initials: H
authors.lastname: Hauser
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.forename: Ruth
authors.initials: R
authors.lastname: Gilderthorp
authors.forename: Lucio
authors.initials: L
authors.lastname: Marcello
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McQuillan
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: Sanders
authors.forename: Andries
authors.initials: A
authors.lastname: van Tonder
authors.forename: Michael L
authors.initials: ML
authors.lastname: Ginger
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
authors.forename: J David
authors.initials: JD
authors.lastname: Barry
authors.forename: Christiane
authors.initials: C
authors.lastname: Hertz-Fowler
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation / Q000235:genetics*; D001483:Base Sequence; D016054:DNA, Protozoan / Q000235:genetics; D019143:Evolution, Molecular; D018503:Genome, Protozoan; D006801:Humans; D057131:Immune Evasion / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology*; D014348:Trypanosoma congolense / Q000235:genetics / Q000276:immunology*; D016689:Trypanosoma vivax / Q000235:genetics / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma