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INITIAL CONDITIONS FOR PARASITISM IN TRYPANOSOMES: APOSSIBLE ROLE OF ANAEROBIC PYRIMIDINE BIOSYNTHESIS

Research Project

Project/Area Number 17590377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionJUNTENDO UNIVERSITY

Principal Investigator

NARA Takeshi  JUNTENDO UNIVERSITY SCHOOL OF MIDICINE, DEPARTMENT OF MOLECULAR AND CELLULAR PARASITOLOGY, ASSOCIATE PROFESSOR, 医学部, 講師 (40276473)

Co-Investigator(Kenkyū-buntansha) ANNOURA Takeshi  JUNTENDO UNIVERSITY SCHOOL OF MIDICINE, DEPARTMENT OF MOLECULAR AND CELLULAR PARASITOLOGY, RESEARCH ASSOCIATE, 医学部, 助手 (90407239)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsTRYPANOSOMES / PYRIMIDINE BIOSYNTHESIS / MOLECULAR EVOLUTION / LATERAL GENE TRANSFER / ADAPTATION FOR PARASITISM
Research Abstract

In this project, we aimed to verify evolutionary implications of de novo pyrimidine biosynthetic pathway, which includes six sequential enzymatic reactions, in trypanosomes. Genes for the fourth and sixth enzymes of the pathway, dihydroorotate dehydrogenase (DHOD) and orotidine-5'-monophosphate decarboxylase (OMPDC), respectively, have been previously shown to have a lateral-gene-transfer (LGT) origin, highlighting the distinct nature of the pathway in trypanosomes. We demonstrated that genetic diversity and the kinetic properties of DHOD in Trypanosoma cruzi, the agent of Chagas' disease. Three DHOD genes in T. cruzi Tulahuen strain were comprised of 942 bp and differed by 26 nucleotides, resulting in replacement of 8 amino acid residues. Recombinant DHODs showed similar enzymatic properties, including optimal pH, optimal temperature, V_<max>, and K_m for the substrate and electron acceptor. These results suggest that, despite their genetic variations, kinetic properties of the three … More T. cruzi DHODs are conserved.
OMPDC gene is fused with the fifth enzyme, orotate phosphoribosyltransferase (OPRT) as OMPDC-OPRT fusion and localized in glycosomes in trypanosomes, while they occur as OPRT-OMPDC fusion in animals and plants. Gene cloning and phylogenetic analyses suggested that OMPDC-OPRT fusion emerged in a common ancestor of kinetoplastids that comprises trypanosomatids and bodonids, via split of OPRT-OMPDC and re-fusion. OMPDC-OPRT fusion was also found in another eukaryotic group, stramenopiles. Phylogenetic reconstruction rejected statistically the monophyly of the OPRT domains of stramenopile and kinetoplastid OMPDC-OPRT, demonstrating that these gene fusions do not share a common evolutionary origin, despite the identical gene order. Thus, the OMPDC-OPRT fusion is likely to have emerged independently in these eukaryotic groups. We conclude that gene fusion events occur more frequently than previously thought and that LGT has made a marked contribution to establishment of the rearranged structure of OPRT and OMPDC genes in eukaryotes. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (20 results)

All 2007 2006 2005 Other

All Journal Article (20 results)

  • [Journal Article] Antibody isotype responses to paramyosin, a vaccine candidate for schistosomiasis, and their correlations with resistance and fibrosis in patients with Schistosoma japonicum in Leyte, the Philippines2007

    • Author(s)
      Takeshi Nara
    • Journal Title

      American Journal of Tropical Medicine and Hygiene 76(2)

      Pages: 384-391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ANTIBODY ISOTYPE RESPONSES TO PARAMYOSIN, A VACCINE CANDIDATE FOR SCHISTOSOMIASIS, AND THEIR CORRELATIONS WITH RESISTANCE AND FIBROSIS IN PATIENTS WITH SCHISTOSOMA JAPONICUM IN LEYTE, THE PHILIPPINES2007

    • Author(s)
      NARA T, ET AL.
    • Journal Title

      AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE 76-2

      Pages: 384-391

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antibody isotype responses to paramyosin, a vaccine cardidate for schistosomiasis, and their correlations eith resistance and fibrosis in patients with Schistosoma japonicum in Leyte, the Philippines2007

    • Author(s)
      Nara T, Iizumi K, Ohmae H, Sy O, Tsubata S, Inaba Y, Tsubouchi A, tanabe M, Kojima S, Aoki T
    • Journal Title

      American Journal of Tropical Medicine and Hygiene 76(2)

      Pages: 384-391

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic diversity and kinetic properties of Trypanosoma cruzi dihydroorotate dehydrogenase isoforms2006

    • Author(s)
      Idalia Sariego
    • Journal Title

      Parasitology International 55(1)

      Pages: 11-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of ouabain-insensitive Na^+-ATPase in the parasitic protist, Trypanosoma cruzi2006

    • Author(s)
      Kyoichi Iizumi
    • Journal Title

      Biochimica et Biophysica Acta 1758(6)

      Pages: 738-746

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] シャーガス病、特集「注目される人獣共通感染症-原虫・プリオン・リケッチア性人獣共通感染症」2006

    • Author(s)
      奈良武司
    • Journal Title

      化学療法の領域 22(8)

      Pages: 1239-1243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] GENETIC DIVERSITY AND KINETIC PROPERTIES OF TRYPANOSOMA CRUZI DIHYDROOROTATE DEHYDROGENASE ISOFORMS2006

    • Author(s)
      SARIEGO I, ETAL.
    • Journal Title

      PARASITOLOGY INTERNATIONAL 55-1

      Pages: 11-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] MOLECULAR CLONING AND CHARACTERIZATION OF OUABAIN-INSENSITIVE NA+-ATPASE IN THE PARASITIC PROTIST, TRYPANOSOMA CRUZI2006

    • Author(s)
      IIZUMI K, ETAL.
    • Journal Title

      BIOCHIMICA ET BIOPHYSICA ACTA 1758-6

      Pages: 738-746

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of ouabain-insensitive Na^+-ATPase in the parasitic protist, Trypanosoma cruzi2006

    • Author(s)
      Iizumi K, Mikami Y, Hashimoto M, Nara T, Hara Y, Aoki T
    • Journal Title

      Biochimica et Biophysica Acta 1758(6)

      Pages: 738-746

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic diversity and kinetic properties of Trypanosoma cruzi dihydroorotate dehydrogenase isoforms2006

    • Author(s)
      Idalia Sariego
    • Journal Title

      Parasitol International 55(1)

      Pages: 11-16

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The origin of dihydroorotate dehydrogenase genes of kinetoplastids, with special reference to their biological significance and adaptation to anaerobic, parasitic conditions2005

    • Author(s)
      Takeshi Annoura
    • Journal Title

      Journal of Molecular Evolution 60(1)

      Pages: 113-127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibitory action of marine algae extracts on the Trypanosoma cruzi dihydroorotate dehydrogenase activity and on the protozoan growth in mammalian cells2005

    • Author(s)
      Takeshi Nara
    • Journal Title

      Parasitology International 54(1)

      Pages: 59-64

    • NAID

      10015455204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression, purification and crystallization of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with orotate2005

    • Author(s)
      Daniel K. Inaoka
    • Journal Title

      Acta Crystallographica Section F 61(10)

      Pages: 875-878

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] THE ORIGIN OF DIHYDROOROTATE DEHYDROGENASE GENES OF KINETOPLASTIDS, WITH SPECIAL REFERENCE TO THEIR BIOLOGICAL SIGNIFICANCE AND ADAPTATION TO ANAEROBIC, PARASITIC CONDITIONS.2005

    • Author(s)
      ANNOURA T, et al.
    • Journal Title

      JOURNAL OF MOLECULAR EVOLUTION 60-1

      Pages: 113-127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] INHIBITORY ACTION OF MARINE ALGAE EXTRACTS ON THE TRYPANOSOMA CRUZI DIHYDROOROTATE DEHYDROGENASE ACTIVITY AND ON THE PROTOZOAN GROWTH IN MAMMALIAN CELLS.2005

    • Author(s)
      NARA T, et al.
    • Journal Title

      PARASITOLOGY INTERNATIONAL 54-1

      Pages: 59-64

    • NAID

      10015455204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EXPRESSION, PURIFICATION AND CRYSTALLIZATION OF TRYPANOSOMA CRUZI DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH OROTATE2005

    • Author(s)
      INAOKA DK, et al.
    • Journal Title

      ACTA CRYSTALLOGRAPHICA SECTION F 61-10

      Pages: 875-878

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression, purification and crystallization of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with orotate2005

    • Author(s)
      Inaoka Daniel K.
    • Journal Title

      Acta Crystallographica Section F 61(10)

      Pages: 875-878

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Occurrence of multiple, independent gene fusion events for the fifth and sixth enzymes of pyrimidine biosynthesis in different eukaryotic groups

    • Author(s)
      Takashi Makiuchi
    • Journal Title

      Gene (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] OCCURRENCE OF MULTIPLE, INDEPENDENT GENE FUSION EVENTS FOR THE FIFTH AND SIXTH ENZYMES OF PYRIMIDINE BIOSYNTHESIS IN DIFFERENT EUKARYOTIC GROUPS

    • Author(s)
      MAKIUCHI T, et al.
    • Journal Title

      GENE (IN PRESS)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Occurrence of multiple, independent gene fusion events for the fifth and sixth enzymes of primidine biosynthesis in different eukaryotic groups

    • Author(s)
      Makiuchi T, Nara T, Annoura T, Hashimoto T, Aoki T
    • Journal Title

      Gene (In press)

    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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