The Genome of the African Trypanosome

Abstract

Trypanosoma brucei is a diploid organism with a nuclear haploid DNA content of 35 ± 9 megabase pairs (Mb) depending on the trypanosome isolate. About 15% of the total cellular DNA is in the kinetoplast where it is organized as homogenous 23-kb maxicircles and heterogeneous 1 -kb minicircles. The remaining 85% of the DNA occurs in the nucleus as linear DNA molecules ranging in size from 50 kb to 6 Mb. At least 11 pairs of megabase chromosomes of 1 to 6 Mb exist that are numbered I-XI from smallest to largest. The two homologues of a megabase chromosome pair can differ in size by as much as 4-fold. Several intermediate-sized chromosomes of 0.2 – 0.9 Mb and uncertain ploidy are also present. The telomeres of the megabase and intermediate chromosomes are linked to expression sites for the genes encoding the variant surface glycoproteins (VSGs). In addition, about 100 linear minichromosomes of 50–150 kb occur and serve as repositories for unexpressed, telomere-linked VSG genes. About 50% of the nuclear genome is coding sequence. To date only one tRNA gene and one protein-encoding gene, specifying poly(A) polymerase, have been found to contain an intron. The complete sequence determination of chromosomes I and II (about 1 Mb each) is nearing completion and more than 20 Mb of discontinuous single-pass genomic DNA sequence data have been generated. Based on analogy with the Leishmania genome, much of the African trypanosome nuclear genome is likely to be arrayed as long transcription units of 50 or more intronless genes. Knowledge of this genomic sequence and its complete set of genes will open many new avenues for identifying better ways to control or eliminate this pathogen and its deadly disease.