Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A Genetic Survey of the Pathogenic Parasite Trypanosoma cruzi
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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. , p. 66
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1264
Keyword [en]
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
Keyword [sv]
Genetik
National Category
Genetics
Research subject
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-3425ISBN: 91-554-5635-9 (print)OAI: oai:DiVA.org:uu-3425DiVA, id: diva2:162763
Public defence
2003-05-23, Rudbeck Hall, Rudbeck Laboratory, Uppsala University, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
List of papers
1. A chromosome-specific dispersed gene family in Trypanosoma cruzi
Open this publication in new window or tab >>A chromosome-specific dispersed gene family in Trypanosoma cruzi
1999 (English)In: Molecular and biochemical parasitology (Print), ISSN 0166-6851, E-ISSN 1872-9428, Vol. 100, no 2, p. 229-234Article in journal (Refereed) Published
Keyword
Trypanosoma cruzi, Genome analysis, Chromosome 3, Dispersed gene family, DGC3
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90414 (URN)10.1016/S0166-6851(99)00049-3 (DOI)10391385 (PubMedID)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2017-12-14Bibliographically approved
2. Gene survey of the pathogenic protozoan Trypanosoma cruzi
Open this publication in new window or tab >>Gene survey of the pathogenic protozoan Trypanosoma cruzi
Show others...
2000 (English)In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 10, no 8, p. 1103-1107Article 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90415 (URN)10.1101/gr.10.8.1103 (DOI)10958628 (PubMedID)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2017-12-14Bibliographically approved
3. Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence
Open this publication in new window or tab >>Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence
2003 (English)In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 87, no 2, p. 269-278Article in journal (Refereed) Published
Abstract [en]

The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T. cruzi CL Brener strain, the reference clone for the genome project. The genes linked to the synthetase appeared to be involved in diverse cell-functions, not part of the trypanothione metabolism. The gene synteny was conserved at both allelic loci that were found to reside on a pair of homologous chromosomes with a size difference of about 2 Mb. The allelic polymorphism of TcTRS resulted in a protein sequence divergence of 4%, ten-times higher than in trypanothione reductase (TR), another key enzyme in the same pathway. Such allelic divergence observed in T. cruzi genes might have implications for drug design against Chagas' disease and the evolutional impact of the CL Brener strain.

Keyword
Trypanosoma cruzi, Trypanothione synthetase, CL Brener, TcTRS-1CL, TcTRS-2CL, Sequence polymorphism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90416 (URN)10.1016/S0001-706X(03)00067-6 (DOI)12826302 (PubMedID)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2017-12-14Bibliographically approved
4. Differential expression of a polypyrimidine binding-like protein in Trypanosoma cruzi during parasite development
Open this publication in new window or tab >>Differential expression of a polypyrimidine binding-like protein in Trypanosoma cruzi during parasite development
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-90417 (URN)
Available from: 2003-04-25 Created: 2003-04-25 Last updated: 2010-01-13Bibliographically approved

Open Access in DiVA

fulltext(1100 kB)1090 downloads
File information
File name FULLTEXT01.pdfFile size 1100 kBChecksum SHA-1
e744b5ffdc17670d9ff05c6599e2023c435a21f52f890b93295cff463f94f114af8bc7ae
Type fulltextMimetype application/pdf
Buy this publication >>

By organisation
Department of Genetics and Pathology
Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 1090 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1006 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf