Telomere length in Trypanosoma brucei

Abstract

Trypanosoma brucei-thwarts the host immune response by replacing its variant surface glycoprotein (VSG). The actively transcribed VSG is located in one of ~20 telomeric expression sites (ES). Antigenic variation can occur by transcriptional switching, reciprocal translocations, or duplicative gene conversion events among ES or with the large repertoire of telomeric and nontelomeric VSG. In recently isolated strains, duplicative gene conversion occurs at a high frequency and predominates, but the switching frequency decreases dramatically upon laboratory-adaptation. Uniquely, T. brucei telomeres grow-apparently indefinitely-at a steady rate of 6-12 base pairs (bp) per population doubling (PD), but the telomere adjacent to an active ES undergoes frequent truncations. Using two-dimensional gel electrophoresis, we demonstrate that all of the chromosome classes of fast-switching and minimally propagated T. brucei have shorter telomeres than extensively propagated Lister 427 clones, suggesting a link between laboratory adaptation, telomere growth, and VSG switching rates.

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

“…In addition, T. brucei telomeres grow by 6–8 bp/PD during growth under laboratory conditions (a process that has only been observed in this organism) [25], [30]. What is distinct between the natural T. brucei lifecycle and their laboratory propagation that could account for the observed differences in telomere lengths?…”

“…Thus it has been suggested that when the telomere of the chromosome harboring the active BES is short the DNA breaks precipitating telomeric deletions would occur upstream of the VSG , resulting in an antigenic switch [24]. This claim was further correlated to the fact that strains of T. brucei that have been recently isolated from nature, who switch at a rate of approximately 10 −2 –10 −3 , have shorter telomeres than laboratory-adapted strains, whose rate of switching can be are 100–10,000-times lower [27], [28], [29], [30]. In all, this suggested an inverse correlation between telomere length and the amount antigenic switching in T. brucei [24], yet there were no data in direct support of this hypothesis.…”

The epigenome of Trypanosoma brucei: A regulatory interface to an unconventional transcriptional machine

“…In contrast to laboratory strains, T. brucei field strains possess shorter telomeres [49], and switch VSGs more frequently [50,51]. A recent study revealed that telomere length is correlated with VSG switching frequency, and demonstrated that the shorter the telomere structure at an active ES, the more frequently VSG switching occurred [52].…”

“…The localization of specific histone variants, modified histones [21] and glycosylated thymidines [49] at sites of pol II transcription initiation and termination is striking. Also, ORC1, implicated in the nucleation of a repressive heterochromatin at the silent mating type loci in S. cerevisiae , was shown to be recruited to PTU flanks as well as the silent VSG arrays in T. brucei .…”

Telomere as an Important Player in Regulation of Microbial Pathogen Virulence

“…In consistence with the hypothesis, several T. brucei strains with only limited propagation in a laboratory (usually called pleomorphic strains) have much higher VSG switching rate (10 -4 to 10 -2 per population doubling) and relatively shorter telomeres (3-12 kb long, with an average of 8-10 kb) (Dreesen & Cross 2008). In contrast, the 427 Lister strain has been extensively propagated in the laboratory, has a VSG switch rate of 10 -6 per generation, and has telomeres ranging 3-20 kb with an average of 15 kb .…”