The African trypanosome genome

The haploid nuclear genome of the African trypanosome, Trypanosoma brucei, is about 35 Mb and varies in size among different trypanosome isolates by a s much as 25%. The nuclear DNA of this diploid organism is distributed amon g three size classes of chromosomes: the megabase chromosomes of which ther e are at least 11 pairs ranging from 1 Mb to more than 6 Mb (numbered I-XI from smallest to largest); several intermediate chromosomes of 200-900 kb a nd uncertain ploidy; and about 100 linear minichromosomes of 50-150 kb. Siz e differences of as much as four-fold can occur, both between the two homol ogues of a megabase chromosome pair in a specific trypanosome isolate and a mong chromosome pairs in different isolates. The genomic DNA sequences dete rmined to date indicated that about 50% of the genome is coding sequence. T he chromosomal telomeres possess TTAGGG repeats and many, if not all, of th e telomeres of the megabase and intermediate chromosomes are linked to expr ession sites for genes encoding variant surface glycoproteins (VSGs). The m inichromosomes serve as repositories for VSG genes since some but not all o f their telomeres are linked to unexpressed VSG genes. A gene discovery pro gram, based on sequencing the ends of cloned genomic DNA fragments, has gen erated more than 20 Mb of discontinuous single-pass genomic sequence data d uring the past year, and the complete sequences of chromosomes I and II (ab out 1 Mb each) in T. brucei GUTat 10.1 are currently being determined, It i s anticipated that the entire genomic sequence of this organism will be kno wn in a few years. Analysis of a test microarray of 400 cDNAs and small ran dom genomic DNA fragments probed with RNAs from two developmental stages of T. brucei demonstrates that the microarray technology can be used to ident ify batteries of genes differentially expressed during the various life cyc le stages of this parasite. Published by Elsevier Science Ltd. All rights r eserved.