The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.
The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.
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DOI：
10.1371/journal.pbio.0000005
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发表时间：
2003-10
期刊：
影响因子：
9.8
通讯作者：
DeRisi, Joseph L
中科院分区：
文献类型：
--
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
恶性疟原虫是最严重的人类疟疾的病原体，每年影响全世界2亿至3亿人。最近对恶性疟原虫的基因组进行了测序，发现了5,400多个基因，其中60%编码功能未知的蛋白质。深入了解这些基因的生化功能和调控将为未来根除这种疾病的药物和疫苗开发工作提供基础。通过分析完整的无性红细胞内发育周期（IDC）转录组的HB 3株恶性疟原虫，我们证明，至少60%的基因组是转录活跃在这个阶段。我们的数据表明，这种寄生虫已经进化出一种非常专门的转录调控模式，产生连续级联的基因表达，从对应于一般细胞过程的基因开始，如蛋白质合成，并以疟原虫特异性功能结束，如参与红细胞入侵的基因。这些数据表明，基因连续沿着染色体很少共调节，而质体基因组的转录是高度共调节，可能是多顺反子。HB3和参考基因组菌株（3D7）之间的比较基因组杂交用于区分IDC期间未表达的基因和由于可能的序列变异而未检测到的基因。发现这些菌株之间的基因组差异几乎完全在染色体的高度抗原性亚端粒区域。在真核生物学中，指导恶性疟原虫无性发育的基因调控的简单级联是前所未有的。IDC的转录组类似于“即时”制造过程，其中任何给定基因的诱导每个循环发生一次，并且仅在需要时发生。据我们所知，这些数据提供了第一个全面的看法，转录的时间在整个红细胞内的恶性疟原虫的发展，并提供了一个资源，用于识别新的化疗和疫苗的候选人。在人类血细胞中疟原虫的生命周期中，基因调控的紧密级联表明许多疟原虫基因具有新的功能
Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a “just-in-time” manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates. A tight cascade of gene regulation during the lifecycle of the malaria parasite in human blood cells suggests new functions for many Plasmodium genes