The mechanism of duplicative VSG gene activation during antigenic variation in Trypanosoma brucei

Burton, Peter (2003) The mechanism of duplicative VSG gene activation during antigenic variation in Trypanosoma brucei. PhD thesis, University of Glasgow.

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Abstract

Trypanosoma brucei is a parasitic protozoan of the order Kinetoplastida. In sub-Saharan Africa it causes nagana in livestock and wild mammals, and sleeping sickness in humans. It is transmitted between mammalian hosts by the tsetse fly vector and during its life in both hosts it proceeds through a unidirectional life cycle, involving several morphological and molecular changes as adaptations to life in different environments. During growth in the mammalian host the parasite undergoes the phenomenon of antigenic variation in order to escape the immune system of the host. A highly immunogenic surface protein known as the variant surface glycoprotein (VSG) is expressed, preventing the immune response from reacting with any other invariant surface proteins. Periodically, the VSG on the surface is altered to one with immunologically distinct epitopes, making the immune response specific to the prior VSG ineffective. VSGS, in the bloodstream form, are expressed from specialised polycistronic, telomeric transcription units named bloodstream expression sites (BESs). There are approximately 20 BESs in the genome, only one of which is active at any time. Different VSG genes can be activated by turning on the expression of a different BES and silencing the previously active one, a process termed in situ switching. There are, however, an estimated 1000 silent VSG genes; some of these reside in the subtelomeres of the minichromosomes whereas the rest are located in chromosome-internal arrays. Chromosome-internal and minichromosomal VSG genes can only be activated by moving the gene sequence into the active BES, replacing the previously expressed VSG. This transposition most frequently occurs through a duplication of the VSG gene. It has been proposed to occur by homologous recombination as sequence homologies appear to mark the limits of such events. The VSG switching rate varies depending on the strain examined, ranging from as rapid as ~2 x 10.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Genetics, Parasitology
Date of Award: 2003
Depositing User: Enlighten Team
Unique ID: glathesis:2003-71386
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 10 May 2019 10:49
URI: http://theses.gla.ac.uk/id/eprint/71386

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