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Medical Microbiology and Immunology

, Volume 190, Issue 1–2, pp 9–12 | Cite as

The Leishmania genome project: new insights into gene organization and function

  • Peter J. Myler
  • Stephen M. Beverley
  • Angela K. Cruz
  • Deborah E. Dobson
  • Alasdair C. Ivens
  • Paul D. McDonagh
  • Rentala Madhubala
  • Santiago Martinez-Calvillo
  • Jeronimo C. Ruiz
  • Alka Saxena
  • Ellen Sisk
  • Susan M. Sunkin
  • Elizabeth Worthey
  • Shaofeng Yan
  • Kenneth D. Stuart
Leishmania and the Leishmaniases

Abstract.

The sequencing of Leishmania major Friedlin chromosome 1 (Chr1), Chr3, and Chr4 has been completed, and several other chromosomes are well underway. The complete genome sequence should be available by 2003. Over 1,000 full-length new genes have been identified, with the majority (~75%) having unknown function. Many of these may be Leishmania (or kinetoplastid) specific. Most interestingly, the genes are organized into large (>100–500 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a "divergent" manner, i.e., the mRNAs for the two sets of genes are both transcribed towards the telomeres. Nuclear run-on analysis suggests that transcription is initiated in both directions within the "divergent" region. Chr3 and Chr4 contain two "convergent" clusters, with a single "divergent" gene at one telomere of Chr3. Sequence analysis of several genes from the LD1 region of Chr35 indicates a high degree of sequence conservation between L. major and L. donovani/L. infantum within protein-coding open reading frames (ORFs), with a lower degree of conservation within the non-coding regions. Immunization of mice with recombinant antigen from two of these genes, BT1 (formerly ORFG) and ORFF, results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania.

Keywords

Leishmaniasis Trypanosoma Brucei Leishmania Gene Leishmania Genome Polycistronic Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Peter J. Myler
    • 1
  • Stephen M. Beverley
    • 2
  • Angela K. Cruz
    • 3
  • Deborah E. Dobson
    • 2
  • Alasdair C. Ivens
    • 4
  • Paul D. McDonagh
    • 1
  • Rentala Madhubala
    • 5
  • Santiago Martinez-Calvillo
    • 1
  • Jeronimo C. Ruiz
    • 3
  • Alka Saxena
    • 1
  • Ellen Sisk
    • 1
  • Susan M. Sunkin
    • 1
  • Elizabeth Worthey
    • 1
  • Shaofeng Yan
    • 1
  • Kenneth D. Stuart
    • 1
  1. 1.Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109-1651, USAUSA
  2. 2.Department of Molecular Microbiology, Washington University School of Medicine, 660S. Euclid Ave., St. Louis, MO 63110-1093, USAUSA
  3. 3.Departamento de Bioquimica, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Sao Paulo, BrazilBrazil
  4. 4.Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UKUK
  5. 5.School of Life Sciences, Jawaharla Nehru University, New Delhi, 110067, IndiaIndia

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