The Fundamental Contribution of Genome Hypervariability to the Success of a Eukaryotic Pathogen,Trypanosoma brucei

Abstract

As a parasite that causes a variety of chronic human and livestock diseases in Africa and elsewhere, the trypanosome needs to overcome a number of grand challenges mounted, directly or indirectly, by its wide range of hosts. In general, the adaptations are all to do with the generation, diversification, and regulation of hypervariant, multigene families, the most important of which encodes thousands of variant surface glycoprotein (VSG) isoforms. To understand how the various interlinked processes in antigenic variation contribute to and are served by genome adaptations, it is necessary first to describe what we know, phenotypically and genotypically, about this variation system. Uniquely to the African trypanosomes that use antigenic variation, there is also a set of minichromosomes, Trypanosoma brucei number ~100. There is a set of potential transcription units, known as bloodstream expression sites (BES), adjacent to the telomeres of some of the megabase chromosomes and numbering 5 to 15 per genome, depending on the strain. The main function of BES is to provide transcription loci for VSG. Mechanisms for singular and differential expression of VSG center on the BES, which emphasizes the pivotal role of the expression site in antigenic variation. Importantly, short indels of a few bases also occur, creating frame-shifting: pseudogene formation. The other types of VSG locus also display signs of change through recombination, although fewer data are available.