| Summary: | Tsetse flies are a type of blood-sucking insect living in diverse locations in sub-Saharan Africa. These insects can transmit the unicellular parasite <i>Trypanosoma brucei</i> (<i>T. brucei</i>) which causes African trypanosomiasis in mammals. There remain huge unmet needs for prevention, early detection, and effective treatments for this disease. Currently, few studies have investigated the molecular mechanisms of parasite–host interactions underlying African trypanosomiasis, mainly due to a lack of understanding of the <i>T. brucei</i> genome. In this study, we dissected the genomic and transcriptomic profiles of <i>T. brucei</i> by annotating the genome and analyzing the gene expression. We found about 5% of <i>T. brucei</i> proteins in the human proteome, while more than 80% of <i>T. brucei</i> protein in other trypanosomes. Sequence alignment analysis showed that 142 protein homologs were shared among <i>T. brucei</i> and mammalian genomes. We identified several novel proteins with pathogenic potential supported by their molecular functions in <i>T. brucei</i>, including 24 RNA-binding proteins and six variant surface glycoproteins. In addition, 26 novel microRNAs were characterized, among which five miRNAs were not found in the mammalian genomes. Topology analysis of the miRNA-gene network revealed three genes (RPS27A, UBA52 and GAPDH) involved in the regulation of critical pathways related to the development of African trypanosomiasis. In conclusion, our work opens a new door to understanding the parasite–host interaction mechanisms by resolving the genome and transcriptome of <i>T. brucei</i>.
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