Co-ordinated programme of gene expression during asexual intraerythrocytic development of the human malaria parasite Plasmodium falciparum revealed by microarray analysis
Co-ordinated programme of gene expression during asexual intraerythrocytic development of the human malaria parasite Plasmodium falciparum revealed by microarray analysis
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DOI：
10.1046/j.1365-2958.2001.02222.x
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发表时间：
2001-01-01
影响因子：
3.6
通讯作者：
Goldberg, DE
中科院分区：
文献类型：
--
作者：
Mamoun, CB;Gluzman, IY;Goldberg, DE
恶性疟原虫是一种原生动物寄生虫，导致人类最严重的疟疾形式。人类感染期间出现的所有临床症状和病理变化都是由疟原虫的无性血液阶段引起的。在宿主红细胞内，寄生虫在成熟过程中经历了巨大的发育变化。为了分析红细胞内发育过程中基因的表达，构建了DNA微阵列，并用阶段特异的cDNAs进行了探测。特定mRNAs的发育上调被发现聚集成功能基团，并揭示了基因表达的协调程序。那些参与蛋白质合成(核糖体蛋白、翻译因子)的基因在发育早期达到顶峰，其次是参与新陈代谢的基因，最显著的是糖酵解基因。黏附/侵袭基因在成熟过程的后期被激活。在红细胞内发育的末期(分裂晚期)，基因表达普遍关闭，尽管有一小部分基因，包括一些蛋白激酶，在这个阶段被激活。几乎所有的基因在发育过程中都表现出一定的调节作用。少数基因保持不变，应该有助于在不同阶段之间实现mRNA水平的正常化。这些数据将有助于对恶性疟原虫基因组的功能分析，并将有助于识别在人类宿主中对寄生虫的发展和繁殖起关键作用的基因。
Plasmodium falciparum is a protozoan parasite responsible for the most severe forms of human malaria. All the clinical symptoms and pathological changes seen during human infection are caused by the asexual blood stages of Plasmodium. Within host red blood cells, the parasite undergoes enormous developmental changes during its maturation. In order to analyse the expression of genes during intraerythrocytic development, DNA microarrays were constructed and probed with stage-specific cDNA. Developmental upregulation of specific mRNAs was found to cluster into functional groups and revealed a co-ordinated programme of gene expression. Those involved in protein synthesis (ribosomal proteins, translation factors) peaked early in development, followed by those involved in metabolism, most dramatically glycolysis genes. Adhesion/invasion genes were turned on later in the maturation process. At the end of intraerythrocytic development (late schizogony), there was a general shut-off of gene expression, although a small set of genes, including a number of protein kinases, were turned on at this stage. Nearly all genes showed some regulation over the course of development. A handful of genes remained constant and should be useful for normalizing mRNA levels between stages. These data will facilitate functional analysis of the P. falciparum genome and will help to identify genes with a critical role in parasite progression and multiplication in the human host.