Comparative Genomics Reveals Multiple Genetic Backgrounds of Human Pathogenicity in the Trypanosoma brucei Complex

Abstract

The Trypanosoma brucei complex contains a number of subspecies with exceptionally variable life histories, including zoonotic subspecies, which are causative agents of human African trypanosomiasis (HAT) in sub-Saharan Africa. Paradoxically, genomic variation between taxa is extremely low. We analyzed the whole-genome sequences of 39 isolates across the T. brucei complex from diverse hosts and regions, identifying 608,501 single nucleotide polymorphisms that represent 2.33% of the nuclear genome. We show that human pathogenicity occurs across a wide range of parasite genotypes, and taxonomic designation does not reflect genetic variation across the group, as previous studies have suggested based on a small number of genes. This genome-wide study allowed the identification of significant host and geographic location associations. Strong purifying selection was detected in genomic regions associated with cytoskeleton structure, and regulatory genes associated with antigenic variation, suggesting conservation of these regions in African trypanosomes. In agreement with expectations drawn from meiotic reciprocal recombination, differences in average linkage disequilibrium between chromosomes in T. brucei correlate positively with chromosome size. In addition to insights into the life history of a diverse group of eukaryotic parasites, the documentation of genomic variation across the T. brucei complex and its association with specific hosts and geographic localities will aid in the development of comprehensive monitoring tools crucial to the proposed elimination of HAT by 2020, and on a shorter term, for monitoring the feared merger between the two human infective parasites, T. brucei rhodesiense and T. b. gambiense, in northern Uganda.

A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda

“…The animal infective form of sleeping sickness, AAT, is caused by multiple Trypanosoma parasites in sub-Saharan Africa, including T. congolense, T. vivax, and T. brucei brucei. The human-infective form of sleeping sickness, HAT, is caused by parasites that are closely related to T. b. brucei (Balmer et al, 2010;Sistrom et al, 2014) with two distinct host-evasion types that cause unique disease symptoms known as "chronic" and "acute" sleeping sickness. Although the parasites that cause these two forms of the human disease are currently known in the literature as subspecies T. b. gambiense and T. b. rhodesiense, respectively, the formal taxonomic rank is under revision (Berriman et al, 2005;Echodu et al, 2015;Gibson, Marshall, Marshall, & Godfrey, 1980;Jackson et al, 2010;Sistrom et al, 2016).…”

Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis

“…b . rhodesiense [52,53]. SRA was an exception, since this antigen was much more reactive to rhodesiense than to gambiense samples.…”

Evolving anti-disease strategies from biochemical pathogenesis of african trypanosomiasis

“…Recently, the pathogenicity of trypanosomes was linked to multiple genes, which implied that the differences in disease processes caused by various trypanosome species might have genetically-based incitement from the parasites. 8 Variation in susceptibility of infected hosts to the pathogenic effects of trypanosomes has a connection with the host's genetic resources. Genetic resistance to African trypanosomiasis is termed trypanotolerance and it occurs in some breeds of livestock, species of wildlife, strains of laboratory animals and humans.…”