Genomic organization and gene function in Leishmania
Genomic organization and gene function in Leishmania
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DOI：
10.1042/bst0280527
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发表时间：
2000-10-01
影响因子：
3.9
通讯作者：
Ivens, A
中科院分区：
文献类型：
--
作者：
Myler, PJ;Sisk, E;Ivens, A
利什曼原虫主要弗里德林基因组的测序正在顺利进行，染色体1 （Chr1）和Chr3已经完全测序，Chr4几乎已经完成。其他几条染色体的测序正在进行中，完整的基因组序列最早将于2003年公布。新发现的基因中有很大一部分（约70%）仍未分类，其中许多可能是利什曼原虫（或着丝质体）特异性的。最有趣的是，这些基因在同一条DNA链上被组织成大的（> -300 kb）多顺反子基因簇。Chr1包含两个以“发散”方式组织的这样的簇，即两组基因的mrna都向端粒转录。Chr3包含两个“趋同”簇，在一个端粒上有一个单一的“发散”基因，两个大簇被一个tRNA基因分开。我们已经鉴定了来自Chr35的LD1（利什曼原虫DNA 1）区域的几个基因。BT1编码一种生物蛋白转运体，ORFF编码一种功能未知的核蛋白。用这些基因的重组抗原免疫小鼠可显著减少利什曼原虫攻击后的寄生虫负担。重组ORFF抗原有望用于血清诊断。我们还开发了四环素调控启动子系统，使我们能够调节利什曼原虫的基因表达。
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 (approximate to 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.