Genomic organization and gene function in Leishmania

• Published in: Biochemical Society transactions Vol. 28; no. 5; p. 527
• Main Authors: Myler, P J, Sisk, E, McDonagh, P D, Martinez-Calvillo, S, Schnaufer, A, Sunkin, S M, Yan, S, Madhubala, R, Ivens, A, Stuart, K
• Format: Journal Article
• Language: English
• Published: England 01.10.2000
• Subjects: Animals; Genes, Protozoan; Genome, Protozoan; Leishmania - genetics; Mice
• ISSN: 0300-5127
• DOI: 10.1042/bst0280527

Sequencing of the Leishmania major Friedlin genome is well underway with chromosome 1 (Chr1) and Chr3 having been completely sequenced, and Chr4 virtually complete. Sequencing of several other chromosomes is in progress and the complete genome sequence may be available as soon as 2003. A large proportion ( approximately 70%) of the newly identified genes remains unclassified, with many of these being potentially Leishmania- (or kinetoplastid-) specific. Most interestingly, the genes are organized into large (>100-300 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. Chr3 contains two 'convergent' clusters, with a single 'divergent' gene at one telomere, with the two large clusters separated by a tRNA gene. We have characterized several genes from the LD1 (Leishmania DNA 1) region of Chr35. BT1 (formerly ORFG) encodes a biopterin transporter and ORFF encodes a nuclear protein of unknown function. Immunization of mice with recombinant antigens from these genes 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.