Telomere Length Affects the Frequency and Mechanism of Antigenic Variation in Trypanosoma brucei

PLoS Pathogens

Oliver Dreesen¹  Catharine E. Boothroyd²  Galadriel A. Hovel-Miner²  Monica Mugnier²  F. Nina Papavasiliou²  George A. M. Cross³ 

[1] Institute of Medical Biology, Immunos, Singapore;Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York, United States of America;Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America

关键词: Telomeres;    Cloning;    Trypanosoma;    Trypanosoma brucei gambiense;    Telomere length;    Southern blot;    Antigenic variation;    Gene conversion;   

DOI  :  10.1371/journal.ppat.1002900

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by “switching” from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC). How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions.

【 授权许可】

CC BY