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

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 (approximately 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, BTI (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.

journal_name

Med Microbiol Immunol

authors

Myler PJ,Beverley SM,Cruz AK,Dobson DE,Ivens AC,McDonagh PD,Madhubala R,Martinez-Calvillo S,Ruiz JC,Saxena A,Sisk E,Sunkin SM,Worthey E,Yan S,Stuart KD

doi

10.1007/s004300100070

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

9-12

issue

1-2

eissn

0300-8584

issn

1432-1831

journal_volume

190

pub_type

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