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.
Subject(s)
Genome, Protozoan , Glutathione/analogs & derivatives , Protozoan Proteins/genetics , Sequence Analysis, DNA , Spermidine/analogs & derivatives , Trypanosoma brucei brucei/genetics , Amino Acids/metabolism , Animals , Antigenic Variation , Antigens, Protozoan/chemistry , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Carbohydrate Metabolism , Chromosomes/genetics , Cytoskeleton/chemistry , Cytoskeleton/genetics , Cytoskeleton/physiology , Ergosterol/biosynthesis , Genes, Protozoan , Glutathione/metabolism , Glycosylphosphatidylinositols/biosynthesis , Humans , Lipid Metabolism , Molecular Sequence Data , Protein Transport , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Pseudogenes , Purines/metabolism , Pyrimidines/biosynthesis , Recombination, Genetic , Spermidine/metabolism , Trypanosoma brucei brucei/chemistry , Trypanosoma brucei brucei/immunology , Trypanosoma brucei brucei/metabolism , Trypanosomiasis, African/parasitologyABSTRACT
The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99-100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters.
