ArticleJournal of molecular evolution2005
The origin of dihydroorotate dehydrogenase genes of kinetoplastids, with special reference to their biological significance and adaptation to anaerobic, parasitic conditions.
Article in Journal of molecular evolution, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 102 citations in OpenAlex.
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Hit-to-Lead Studies of Pyrazinylpiperazines against Visceral Leishmaniasis: Pharmacokinetic Profile andACS pharmacology & translational science · 2025Article
- Molecular Dynamics Studies onACS omega · 2025Article
- Class-II dihydroorotate dehydrogenases from three phylogenetically distant fungi support anaerobic pyrimidine biosynthesis.Fungal biology and biotechnology · 2021Article
- In vivo efficacy of combination therapy with albendazole and atovaquone against primary hydatid cysts in mice.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Anaerobic peroxisomes inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Untargeted LC-MS metabolomic studies of Asteraceae species to discover inhibitors of Leishmania major dihydroorotate dehydrogenase.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Identification of candidate pathogenicity determinants of Rhizoctonia solani AG1-IA, which causes sheath blight disease in rice.Current genetics · 2018Article
- Crystal structures of FMN-bound and FMN-free forms of dihydroorotate dehydrogenase fromFEBS open bio · 2018Article
- Fresh insights into the pyrimidine metabolism in the trypanosomatids.Parasites & vectors · 2018Review
- Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets.Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology · 2017Review
- Drug search for leishmaniasis: a virtual screening approach by grid computing.Journal of computer-aided molecular design · 2016Article
- Article
- Genome evolution in trypanosomatid parasites.Parasitology · 2015Review
- Pharmacophore modeling for anti-Chagas drug design using the fragment molecular orbital method.PloS one · 2015Article
- Revisiting the central metabolism of the bloodstream forms of Trypanosoma brucei: production of acetate in the mitochondrion is essential for parasite viability.PLoS neglected tropical diseases · 2013Article
- Biochemical and molecular characterization of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase from Toxoplasma gondii.Molecular and biochemical parasitology · 2012Article
- Genetic dissection of pyrimidine biosynthesis and salvage in Leishmania donovani.The Journal of biological chemistry · 2012Article
- SUMOylation of paraflagellar rod protein, PFR1, and its stage-specific localization in Trypanosoma cruzi.PloS one · 2012Article
- Knockout of the dhfr-ts gene in Trypanosoma cruzi generates attenuated parasites able to confer protection against a virulent challenge.PLoS neglected tropical diseases · 2011Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma cruzi dihydroorotate dehydrogenase (DHOD), the fourth enzyme of the de novo pyrimidine biosynthetic pathway, is localized in the cytosol and utilizes fumarate as electron acceptor (fumarate reductase activity), while the enzyme from other various eukaryotes is mitochondrial membrane-linked. Here we report that DHOD-knockout T. cruzi did not express the enzyme protein and could not survive even in the presence of pyrimidine nucleosides, substrates for the potentially active salvage pathway, suggesting a vital role of fumarate reductase activity in the regulation of cellular redox balance. Cloning and phylogenetic analysis of euglenozoan DHOD genes showed that the euglenoid Euglena gracilis had a mitochondrial DHOD and that biflagellated bodonids, a sister group of trypanosomatids within kinetoplastids, harbor the cytosolic DHOD. Further, Bodo saliens, a bodonid, had an ACT/DHOD gene fusion encoding aspartate carbamoyltransferase (ACT), the second enzyme of the de novo pyrimidine pathway, and DHOD. This is the first report of this novel gene structure. These results are consistent with suggestions that an ancient common ancestor of Euglenozoa had a mitochondrial DHOD whose descendant exists in E. gracilis and that a common ancestor of kinetoplastids (bodonids and trypanosomatids) subsequently acquired a cytosolic DHOD by horizontal gene transfer. The cytosolic DHOD gene thus acquired may have contributed to adaptation to anaerobiosis in the kinetoplastid lineage and further contributed to the subsequent establishment of parasitism in a trypanosomatid ancestor. Different molecular strategies for anaerobic adaptation in pyrimidine biosynthesis, used by kinetoplastids and by euglenoids, are discussed. Evolutionary implications of the ACT/DHOD gene fusion are also discussed.
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