DNA rearrangements of the variable surface antigen genes of the trypanosomes.
DNA rearrangements of the variable surface antigen genes of the trypanosomes.
复制标题
锥虫可变表面抗原基因的 DNA 重排。
DOI：
10.1111/j.1550-7408.1984.tb04291.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Donelson,JE
中科院分区：
文献类型：
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作者：
Murphy,WJ;Brentano,ST;Rice-Ficht,AC;Dorfman,DM;Donelson,JE
锥虫基因组包含数百个(也许数千个)锥体可变表面糖蛋白(VSGs)基因。在单个锥虫体中，这些基因中只有一个在给定的时刻表达；其他基因在转录上是沉默的。这种差异的基因表达是锥虫所表现出的抗原顺序变异的原因。它是由两种类型的VSG基因的基因组重排所介导的。最被理解的重排类型是形成转录活性的表达相关的额外拷贝(ELC)的转录沉默的基本拷贝(BC)基因。这种复制和易位事件将ELC放在染色体末端(端粒)附近，显然它位于强大启动子的下游。一些VSG基因不通过这种ELC机制表达。这些似乎已经接近端粒的基因，被一种不同类型的非复制相关(NDA)机制激活。我们已经使用重组DNA技术克隆和确定了ELC和NDA机制表达的基因序列。对这些序列的比较表明，VSG编码区两侧的序列相似。这表明这两种表达机制之间存在序列相关性。我们还表明，当通过ELC机制表达特定VSG的血流锥体在培养中建立时，所产生的原环锥体迅速停止合成VSG mRNA(和VSG)，但保留VSG基因的ELC。这表明ELC的转录可以在不丢失该ELC的情况下停止，并可能表明存在调节VSG基因转录的其他因素。
The trypanosome genome contains several hundred (and perhaps several thousand) genes for the trypanosome variable surface glycoproteins (VSGs). In an individual trypanosome only one of these genes is expressed at a given instant; the others are transcriptionally silent. This differential gene expression is responsible for the sequential antigenic variation displayed by trypanosomes. It is mediated by two types of genomic rearrangements of these VSG genes. The best understood rearrangement type is the formation of a transcriptionally‐active expression‐linked extra copy (ELC) of a transcriptionally‐silent basic copy (BC) gene. This duplication and translocation event places the ELC near a chromosomal end (a telomere) where it is apparently located downstream from a strong promotor. Some VSG genes are not expressed via this ELC mechanism. These genes, which seem to already be near telomeres, are activated by a different non‐duplication associated (NDA) type of mechanism. We have used recombinant DNA techniques to clone and determine the sequences of genes expressed by both the ELC and NDA mechanisms. Comparison of these sequences reveals that sequences flanking the VSG coding regions are similar. This indicates that there is a sequence correlation between the two mechanisms of expression. We have also shown that when bloodstream trypanosomes expressing a specific VSG via the ELC mechanism are established in culture the resultant procyclic trypanosomes rapidly stop synthesizing the VSG mRNA (and the VSG) but retain the ELC of the VSG gene. This demonstrates that transcription of an ELC can cease without the loss of that ELC and may indicate the presence of other factors regulating VSG gene transcription.