TY - JOUR
T1 - The Leishmania genome project
T2 - New insights into gene organization and function
AU - Myler, Peter J.
AU - Beverley, Stephen M.
AU - Cruz, Angela K.
AU - Dobson, Deborah E.
AU - Ivens, Alasdair C.
AU - McDonagh, Paul D.
AU - Madhubala, Rentala
AU - Martinez-Calvillo, Santiago
AU - Ruiz, Jeronimo C.
AU - Saxena, Alka
AU - Sisk, Ellen
AU - Sunkin, Susan M.
AU - Worthey, Elizabeth
AU - Yan, Shaofeng
AU - Stuart, Kenneth D.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035171871&partnerID=8YFLogxK
U2 - 10.1007/s004300100070
DO - 10.1007/s004300100070
M3 - Article
C2 - 11770120
AN - SCOPUS:0035171871
VL - 190
SP - 9
EP - 12
JO - Medical Microbiology and Immunology
JF - Medical Microbiology and Immunology
SN - 0300-8584
IS - 1-2
ER -