Study probes Trypanosoma genome for causes of human infectivity

Trypanosoma brucei Sleeping sickness, or Human African Trypanosomiasis, is a disease affecting the health and productivity of poor people in many rural areas of sub-Saharan Africa. The disease is caused by a single-celled flagellate, Trypanosoma brucei, which evades the immune system by periodically switching the proteins on its surface. Researchers have produced a genome sequence for T. brucei gambiense, which is the particular subspecies causing most disease in humans. They compared this with an existing reference genome for a non-human infecting strain to identify genes in T. b. gambiense that might explain its ability to infect humans and to assess how well the reference performs as a universal plan for all T. brucei. The genome sequences differ only due to rare insertions and duplications and homologous genes are over 95% identical on average. The archive of surface antigens that enable the parasite to switch its protein coat is remarkably consistent, even though it evolves very quickly. They also identified genes with predicted cell surface functions that are only present in T. b. brucei and have evolved rapidly in recent time. These genes might help to explain variation in disease pathology between different T. brucei strains in different hosts.

The team wanted to answer two questions: Is the existing T. b. brucei sequence representative of the full diversity of T. brucei parasites? And, is there anything in the T. b. gambiense genome that might explain its ability to infect and thrive in human populations? Historically, sleeping sickness has been a severely neglected disease, with considerable impact on human health and the well-being, and prosperity of communities. The genome comparison revealed a remarkable level of similarity between T. b. brucei and T. b. gambiense – just a single locus was unique to T. b. brucei. Moreover, the sequences of comparable genes were, on average, 98.2% identical. Because the genomes were so similar, the team could say with confidence that the T. b. brucei parasite and its genome are good models for future experiments to understand the biology of T. b. gambiense. The similarity between the two genomes also suggested that the source of T. b. gambiense’s ability to infect humans cannot be explained simply by the addition or removal of a few genes. Changes in the phenotype – the physical characteristics – seem to be down to more subtle changes in genetic information. Single letter changes in the genome; differences in the number of copies of genes; changes in how the activity of genes is regulated – all of these genetic nuances could play that crucial role in determining why T. b. gambiense behaves so differently to T. b. brucei. With two high-quality reference genome sequences in place for the T. brucei strains, the search for those small genetic differences is given a boost. It is this search that will fuel the pursuit of targeted drug treatments to tackle T. b. gambiense.

The Genome Sequence of Trypanosoma brucei gambiense, Causative Agent of Chronic Human African Trypanosomiasis. 2010 PLoS Negl Trop Dis 4(4): e658. doi:10.1371/journal.pntd.0000658

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About Alan Cann

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