The Genome of the African Trypanosome <i>Trypanosoma brucei</i>

TLDR

African trypanosomes cause sleeping sickness and livestock disease in sub‑Saharan Africa and possess large subtelomeric arrays of ~806 VSG genes, most of which are pseudogenes that can recombine to generate mosaic variants for immune evasion. The study sequenced and analyzed the 11 megabase chromosomes of *Trypanosoma brucei*. The 26‑megabase genome encodes 9,068 genes, ~900 pseudogenes, and ~1,700 species‑specific genes, and comparative analyses reveal major cytoskeletal and metabolic differences, bacterial gene acquisitions, and several novel drug‑target candidates.

Abstract

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.