Genomic organization and gene function in Leishmania.
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.
Myler
P J
PJ
Seattle Biomedical Research Institute, 4 Nickerson Street, Seattle, WA 98109-1651, USA. mylepj@sbri.org
Sisk
E
E
McDonagh
P D
PD
Martinez-Calvillo
S
S
Schnaufer
A
A
Sunkin
S M
SM
Yan
S
S
Madhubala
R
R
Ivens
A
A
Stuart
K
K
D000818:Animals; D017125:Genes, Protozoan; D018503:Genome, Protozoan; D007891:Leishmania / Q000235:genetics*; D051379:Mice