telomere length affects the frequency and mechanism of antigenic variation in trypanosoma brucei端粒长度影响抗原变异的频率和机制在锥虫属brucei.pdf

Telomere Length Affects the Frequency and Mechanism of Antigenic Variation in Trypanosoma brucei 1 1 1 2 Galadriel A. Hovel-Miner , Catharine E. Boothroyd , Monica Mugnier , Oliver Dreesen , 3 1 George A. M. Cross , F. Nina Papavasiliou * 1 Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York, United States of America, 2 Institute of Medical Biology, Immunos, Singapore, 3 Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America Abstract 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 genet