Sequencing of Trypanosoma brucei rhodesiense genomes reveal haplotypes shared with other subspecies that associate with clinical phenotype

Samples of T. brucei rhodesiense from an outbreak in Uganda in the 1980s were associated with either chronic or acute disease. We demonstrate that they also show differential disease progression and elicit different immune responses in mice and these differences are correlated with the frequencies of slender and stumpy parasite forms. Samples associated with the different virulence phenotypes have been classified into discrete zymodemes however they were indistinguishable using microsatellites. Full genome sequencing of two isolates demonstrates that certain chromosomes do have distinct haplotypes, and SNP genotyping showed that some of these haplotypes associate with the different virulence phenotypes. While it has been shown recently that T. b. brucei and T. b rhodesiense populations undergo genetic exchange in natural populations, our comparative analysis of the T. b rhodesiense genome places these strains between the reference genome sequences of T. b gambiense and T. b. brucei and that some haplotypes are more similar to T. b gambiense. Analysis of SNP markers in a panel of isolates further confirms a mixture of East African and West African genotypes. This suggests that human infective subspecies of T. brucei are not genetically isolated. This has major implications for the control of the parasite, the spread of drug resistance and understanding the variation in virulence and the emergence of human infectivity.