The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense

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.

VAPPER: High-throughput variant antigen profiling in African trypanosomes of livestock

“…Ideally, the user would provide their own reference genome for the mapping step. Because that is not always possible, especially for field isolate analysis, we provide 2 reference genomes, the IL3000 Kenyan isolate [7, 29] and the Tc1/148 (MBOI/NG/60/1-148) Nigerian isolate [30, 31]. Choosing the most adequate reference for the sample being analysed may potentially improve VAPPER results by increasing mapping sensitivity.…”

VAPPER: High-throughput Variant Antigen Profiling in African trypanosomes

“…Ideally, the user would provide their own reference genome for the mapping step. As that is not always possible, especially for field isolate analysis, we provide two reference genomes, the IL3000 Kenyan isolate [14, 28], and the Tc1/148 Nigerian isolate [29, 30]. Choosing the most adequate reference for the sample being analysed may potentially improve the VAPPER results by increasing mapping sensitivity.…”

African trypanosomes

“…The recent advances in culture techniques and genetic manipulation of T. congolense [87, 88] and T. vivax [89] will enable similar strides to be made in the understanding of the distinct cell biology of these important veterinary pathogens. Each African trypanosome species has developed significant and surprisingly distinct adaptations to their hosts, for example in their predicted surface-expressed proteins [90] and VSG gene archive and expression architecture [91, 92]. Each also shows a distinct developmental path in their tsetse fly vector [9].…”