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Gene survey of the pathogenic protozoan Trypanosoma cruzi
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2000 (English)In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 10, no 8, 1103-1107 p.Article in journal (Refereed) Published
Abstract [en]

We have performed a survey of the active genes in the important human pathogen Trypanosoma cruzi by analyzing 5013 expressed sequence tags (ESTs) generated from a normalized epimastigote cDNA library. Clustering of all sequences resulted in 771 clusters, comprising 54% of the ESTs. In total, the ESTs corresponded to 3054 transcripts that might represent one-fourth of the total gene repertoire in T. cruzi. About 33% of the T. cruzi transcripts showed similarity to sequences in the public databases, and a large number of hitherto undiscovered genes predicted to be involved in transcription, cell cycle control, cell division, signal transduction, secretion, and metabolism were identified. More than 140 full-length gene sequences were derived from the ESTs. Comparisons with all open reading frames in yeast and in Caenorhabditis elegans showed that only 12% of the T. cruzi transcripts were shared among diverse eukaryotic organisms. Comparison with other kinetoplastid sequences identified 237 orthologous genes that are shared between these evolutionarily divergent organisms. The generated data are a useful resource for further studies of the biology of the parasite and for development of new means to combat Chagas' disease.

Place, publisher, year, edition, pages
2000. Vol. 10, no 8, 1103-1107 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-90415DOI: 10.1101/gr.10.8.1103PubMedID: 10958628OAI: oai:DiVA.org:uu-90415DiVA: diva2:162760
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2014-10-02Bibliographically approved
In thesis
1. A Genetic Survey of the Pathogenic Parasite Trypanosoma cruzi
Open this publication in new window or tab >>A Genetic Survey of the Pathogenic Parasite Trypanosoma cruzi
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Trypanosoma cruzi, the causative agent of Chagas´ disease, is an evolutionarily ancient species with distinct biological and immunological characteristics. A fundamental understanding of the basic biology of the parasite is necessary in order to develop reliable therapeutic and prophylactic agents against T. cruzi. We have, as a part of the T. cruzi genome project launched by the WHO, generated ESTs corresponding to about one third of the functional genes in the parasite. Only about 1/3 of the unique ESTs could be assigned a function upon sequence comparison to all publicly available data. Comparative analysis of the ESTs to functional genes in S. cerevisiae and C. elegans as well as to sequence data from all other kinetoplastids provided primary insights into the evolutionary divergence of T. cruzi.

A novel dispersed gene family (DGC3) was identified and shown to be present specifically on chromosome 3 and its homologue. Sequence analysis of ten isolated DGC3 genes revealed a high sequence similarity of almost 98% among copies. The DGC3 genes were transcribed, trans-spliced with the spliced leader and polyadenylated, but did not seem to have any protein-coding property. These data preliminary suggest that it encodes a novel family of functional RNA.

In the T. cruzi CL Brener strain, the two alleles of a single copy gene encoding the trypanothione synthetase (TcTRS) enzyme appeared to be highly polymorphic. The divergence of the deduced protein sequence was 4%, almost ten-fold higher than another protein, trypanothione reductase, involved in the same pathway. The observed allelic divergence might influence the TcTRS activity thereby having implications for drug design. Moreover, the TcTRS gene was found to be flanked by a number of genes involved in diverse functions and located to a pair of homologous chromosomes with a size difference of about 2 Mbp.

A gene potentially encoding the polypyrimidine-binding protein (TcPTB) was identified and characterised regarding its organisation and function. The deduced amino acid sequence was shown to comprise four RRM domains generally present in other PTBs. Interestingly, the TcPTB gene appeared to be expressed in a stage-specific manner implicating different functions during parasite development.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 66 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1264
Molecular genetics, Trypanosoma cruzi, Chagas', gene discovery, EST, sequencing, DGC3, repeats, gene family, CL Brener, trypanothione synthetase, TcTRS locus, alleles, polymorphism, RNA-binding protein, TcPTB, stage-specific expression, Genetik
National Category
Research subject
Medical Genetics
urn:nbn:se:uu:diva-3425 (URN)91-554-5635-9 (ISBN)
Public defence
2003-05-23, Rudbeck Hall, Rudbeck Laboratory, Uppsala University, Uppsala, 13:15
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved

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