Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei

Here we present a comprehensive analysis of mRNA expression in several stages of parasite development. Utilizing microarrays that have multiple copies of multiple probes for each gene, we were able to demonstrate with a high degree of statistical confidence that approximately one-fourth of genes show differences in mRNA expression levels in the stages examined. These include complex patterns of gene expression within gene families, including the large family of variant surface glycoproteins (VSGs) and their relatives, where we have identified a number of constitutively expressed family members. Furthermore, we were able to assess the relative abundance of all transcripts in each stage, identifying the genes that are either weakly or highly expressed. Very few genes show no evidence of expression.Despite the lack of gene regulation at the level of transcription initiation, our results reveal extensive regulation of mRNA abundance associated with different life cycle and growth stages. In addition, analysis of variant surface glycoprotein gene expression reveals a more complex picture than previously thought. These data provide a valuable resource to the community of researchers studying this lethal agent.Trypanosoma brucei subspecies are unicellular pathogens that infect humans, as well as domestic and wild animals. The infections of humans are fatal without treatment, and the treatments are suboptimal due to resistance, toxicity, and cost. Furthermore, no vaccine is available due to rampant antigenic variation in which hundreds of variant surface glycoproteins (VSGs) are sequentially displayed on the parasite surface [1]. Additionally, this group of organisms, along with their relatives Trypanosoma congolense and Trypanosoma vivax, have hampered the development of sub-Saharan Africa by their severe effects on cattle and draft animals.In both the mammalian host and the insect vector (tsetse fly), T. brucei undergoes multiple developmental changes that are reflected b