LaCount D J, El-Sayed N M, Kaul S, Wanless D, Turner C M, Donelson J E
Department of Biochemistry, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
Nucleic Acids Res. 2001 May 15;29(10):2012-9. doi: 10.1093/nar/29.10.2012.
African trypanosomes evade the immune response of their mammalian hosts by sequentially expressing genes for different variant surface glycoproteins (VSGs) from telomere-linked VSG expression sites. In the Trypanosoma brucei clone whose genome is being sequenced (GUTat 10.1), we show that the expressed VSG (VSG 10.1) is duplicated from a silent donor VSG located at another telomere-linked site. We have determined two 130 kb sequences representing the VSG 10.1 donor and expression sites. The telomere-linked donor VSG 10.1 resembles metacyclic VSG expression sites, and is preceded by a cluster of 35 or more tandem housekeeping genes, all of which are transcribed away from the telomere. The 45 kb telomere-linked VSG 10.1 expression site contains a promoter followed by seven expression site-associated genes (ESAGs), three pseudo ESAGs, two pseudo VSGs and VSG 10.1. The 80 kb preceding the expression site has few, if any, functional ORFs, but contains 50 bp repeats, INGI retrotransposon-like elements, and novel 4-12 kb repeats found near other telomeres. This analysis provides the first look over a 130 kb range of a telomere-linked donor VSG and its corresponding telomere-linked VSG expression site and forms the basis for studies on antigenic variation in the context of a completely sequenced genome.
非洲锥虫通过从端粒相连的可变表面糖蛋白(VSG)表达位点依次表达不同的VSG基因,来逃避其哺乳动物宿主的免疫反应。在其基因组正在被测序的布氏锥虫克隆(GUTat 10.1)中,我们发现表达的VSG(VSG 10.1)是从位于另一个端粒相连位点的沉默供体VSG复制而来的。我们已经确定了代表VSG 10.1供体和表达位点的两个130 kb序列。端粒相连的供体VSG 10.1类似于循环后期VSG表达位点,并且在其前面有一组35个或更多的串联管家基因,所有这些基因都是从端粒转录出去的。45 kb的端粒相连的VSG 10.1表达位点包含一个启动子,后面跟着七个表达位点相关基因(ESAG)、三个假ESAG、两个假VSG和VSG 10.1。表达位点前面的80 kb区域即使有功能开放阅读框也很少,但包含50 bp重复序列、INGI类逆转座子元件以及在其他端粒附近发现的新的4 - 12 kb重复序列。该分析首次审视了一个130 kb范围内的端粒相连的供体VSG及其相应的端粒相连的VSG表达位点,并为在完全测序基因组背景下研究抗原变异奠定了基础。