Abstract
African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as “Expression Site Associated Genes (ESAGs)”, are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.
Highlights
Many eukaryotic genomes display a distinct elaboration of the subtelomere, the region between chromosomal cores and the telomeres, through the accumulation of species-specific, contingency gene families (Das et al 2008; Brown et al 2010).This is especially true for parasites, in which multicopy gene families are often implicitly associated with virulence and mechanisms for pathogenesis and immuno-modulation (Rehmeyer et al 2006; Sargeant et al 2006; Hayashida et al 2013; Reid 2015)
We describe a conserved telomeric region associated with Variant Surface Glycoproteins (VSGs) loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; these are not orthologous to T. brucei Expression Site Associated Genes (ESAGs)
In T. brucei, $70% of VSG are either frameshifted or fragmentary pseudogenes (Berriman 2005), and this includes many found adjacent to telomeres in expression sites (Hertz-Fowler et al 2008). In both T. congolense strains, we find that most (62%/93%) VSG found in conserved telomeric regions are intact genes predicted to encode functional VSG, which is consistent with the much lower prevalence of pseudogenes across the genome compared with VSG in
Summary
Many eukaryotic genomes display a distinct elaboration of the subtelomere, the region between chromosomal cores and the telomeres, through the accumulation of species-specific, contingency gene families (Das et al 2008; Brown et al 2010). This is especially true for parasites, in which multicopy gene families are often implicitly associated with virulence and mechanisms for pathogenesis and immuno-modulation (Rehmeyer et al 2006; Sargeant et al 2006; Hayashida et al 2013; Reid 2015). Evol. 10(9):2458–2473. doi:10.1093/gbe/evy186 Advance Access publication August 25, 2018
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