VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei

VSG gene control and infectivity strategy of metacyclic stage Trypanosoma brucei
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DOI:
10.1016/s0166-6851(97)00193-x
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发表时间:
1998-03-01
影响因子:
1.5
通讯作者:
Wymer, B
Wymer, B
中科院分区:
医学4区
文献类型:
--
作者:
Barry, JD;Graham, SV;Wymer, B

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由于在采采蝇唾液腺中发育的亚循环锥虫阶段,它启动了变体表面糖蛋白(VSG)的表达,并且通过每个细胞随机激活一个来自亚循环VSG(M-VSG)基因的小子集来实现。尽管血流中单个VSG基因的差异激活作为时间的函数发生,以避免抗体波,但据信,在元循环阶段的目的是同时产生群体多样性。M-VSG基因在其端粒位点被激活,属于单顺反子转录单位,不像所有其他已知的锥虫蛋白编码基因,其似乎是多顺反子转录。这些亚环表达位点的启动子具有独特的性质。在这个生物体中,在生命周期的特定阶段模式中被打开和关闭。我们发现1.22 M-ES启动子在不同的生命周期阶段受到调控,通过启动子的不同元件以及受其基因组位点的影响而发挥差异控制作用。我们对含有1.22和1.61 M-ES的端粒进行了详细的表征,M-ES的上游可能是一个单倍体的非转录区,其中含有一些与血流VSG表达位点相关基因(ESAG)同源的简并序列。进一步上游(分别在1.22和1.61 VSG基因上游22和13 kb)是α-鹅膏蕈碱敏感的转录单位,其可以是多顺反子并且在所有检查的生命周期阶段中转录。它们含有许多基因。元循环和血流ES之间的差异可能有重要的后果,生活周期的调节,遗传稳定性,表型的复杂性和适应性的元循环阶段,因为它感染不同的宿主物种。(C)1998年Francqui基金会。由Elsevier Science B. V.出版,版权所有。
As the metacyclic trypanosome stage develops in the tsetse fly salivary glands, it initiates expression of variant surface glycoproteins (VSGs) and does so by each cell activating, at random, one From a small subset of metacyclic VSG (M-VSG) genes. Whereas differential activation of individual VSG genes in the bloodstream occurs as a function of time, to evade waves of antibody, it is believed that the aim in the metacyclic stage is simultaneously to generate population diversity. M-VSG genes are activated in their telomeric loci and belong to monocistronic transcription units, unlike all other known trypanosome protein-coding genes, which appear to be transcribed polycistronically. The promoters of these metacyclic expression sites (M-ESs) have the unique property. in this organism, of being switched on and off in a life-cycle stage specific pattern. We have found that the 1.22 M-ES promoter is regulated according to life cycle stage, differential control bring exerted through different elements of the promoter and under the influence of its genomic locus. We have characterized in detail the telomeres containing the 1.22 and 1.61 M-ESs. Upstream of the M-ES is a possibly haploid, non-transcribed region with some degenerate sequences homologous with expression site associated genes (ESAGs) that occur in bloodstream VSG expression sites. Further upstream (respectively, 22 and 13 kb upstream of the 1.22 and 1.61 VSG genes) are alpha-amanitin sensitive transcription units that may be polycistrons and are transcribed in all examined life cycle stages. They contain a number of genes. The differences between metacyclic and bloodstream ESs may have important consequences for life cycle regulation, genetic stability, phenotype complexity and adaptability of the metacyclic stage as it infects different host species. (C) 1998 Francqui Foundation. Published by Elsevier Science B.V. All rights reserved.