Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5′ flanking sequences
Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5′ flanking sequences
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DOI：
10.1016/s0166-6851(00)00176-6
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发表时间：
2000-03-15
影响因子：
1.5
通讯作者：
Beck, HP
中科院分区：
文献类型：
--
作者：
Voss, TS;Thompson, JK;Beck, HP
大约50个高度多样化的var基因分布在疟原虫的单倍体基因组中，编码位于受感染红细胞表面的PfEMP 1变体。PfEMP 1参与寄生红细胞的细胞粘附，并通过var基因的差异表达经历抗原变异。var基因家族的成员位于4、7、8和12号染色体的染色体内部位置，以及所有染色体的亚端粒区域。在这里，我们发现有两种不同的和保守的类型的5'上游区的mi基因（var 17型和5 B1型），并建议，大多数subtelomerical var基因侧翼的var 17型5'上游序列。相比之下，5 B1型5'上游定位于已显示在染色体内部区域内含有var基因的染色体。用RT-PCR的转录分析表明，var基因两侧的任一类型的5'上游序列转录在体外培养的滋养体阶段的寄生虫。此外，我们已经表明，4个不同的var基因的5'侧翼序列能够驱动猫报告基因的瞬时表达。我们的研究结果表明，至少var基因转录所需的最小调控序列在cai基因家族的两个亚群中是保守的。此外，这些序列为研究cai基因的染色体结构提供了新的标记。(C)2000 Elsevier Science B. V.保留所有权利。
Approximately 50 highly diverse var genes distributed throughout the haploid genome of the malaria parasite Plasmodium falciparum code for PfEMP1 variants located on the surface of infected erythrocytes. PfEMP1 is involved in cytoadherence of parasitised red blood cells and undergoes antigenic variation through differential expression of var genes. Members of the var gene family are located in chromosome-internal positions on chromosomes 4, 7, 8 and 12, and in subtelomeric regions of all chromosomes. Here we show that there are two distinct and conserved types of 5' upstream regions (var 17-type and 5B1-type) of mi genes, and suggest that most subtelomeric var genes are flanked by a var 17-type 5' upstream sequence. In contrast, 5B1-type 5' upstream are localised to chromosomes that have been shown to contain var genes within chromosome-internal regions. Transcriptional analysis using RT-PCR revealed that var genes flanked by either type of 5' upstream sequence are transcribed in in vitro cultured trophozoite stage parasites. In addition, we have shown that the 5' flanking sequences of four different var genes are able to drive transient expression of the cat reporter gene. Our results suggest that at least the minimal regulatory sequences required for transcription of var genes are conserved among both subgroups of the cai gene family. Furthermore, these sequences provide new markers for the investigation of the chromosomal organisation of cai genes. (C) 2000 Elsevier Science B.V. All rights reserved.