Telomeric Expression Sites Are Highly Conserved in Trypanosoma brucei

• DOI: 10.1371/journal.pone.0003527
• Publication Date: 2008-10-24T17:07:37Z
• Authors: Christiane Hertz-...; Luisa M. Figueiredo; Michael A. Quail; Marion Becker; Andrew Jackson; Nathalie Bason; Karen Brooks; Carol Churcher; Samah Fahkro; Ian Goodhead; Paul Heath; Magdalena Kartvel...; Karen Mungall; David Harris; Heidi Hauser; Mandy Sanders; David Saunders; Kathy Seeger; Sarah Sharp; Jesse E. Taylor; Danielle Walker; Brian White; Rosanna Young; George A. M. Cross; Gloria Rudenko; J. David Barry; Edward J. Louis; Matthew Berriman
• Keywords: 570; 572; General Science & Technology; Science; Trypanosoma brucei brucei; 610; Cell Line; Host-Parasite Interactions; 03 medical and health sciences; MD Multidisciplinary; Animals; Gene Silencing; Cloning, Molecular; Conserved Sequence; Phylogeny; Sequence Tagged Sites; 0303 health sciences; Science & Technology; Q; R; Molecular; Chromosome Mapping; DNA; Sequence Analysis, DNA; Telomere; Antigenic Variation; QR; Multidisciplinary Sciences; Gene Expression Regulation; Science & Technology - Other Topics; Medicine; Transcription Initiation Site; Sequence Analysis; Cloning; Research Article

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.