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抗原变异与非洲锥虫基因组

Antigenic variation and the African trypanosome genome.

作者信息

Donelson John E

机构信息

Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.

出版信息

Acta Trop. 2003 Mar;85(3):391-404. doi: 10.1016/s0001-706x(02)00237-1.

DOI:10.1016/s0001-706x(02)00237-1
PMID:12659976
Abstract

African trypanosomes are protozoan parasites that reside in the mammalian bloodstream where they constantly confront the immune responses directed against them. They keep one-step-ahead of the immune system by continually switching from the expression of one variant surface glycoprotein (VSG) on their surface to the expression of another immunologically distinct VSG-a phenomenon called antigenic variation. About 1000 VSG genes (VSGs) and pseudo-VSGs are scattered throughout the trypanosome genome, all of which are transcriptionally silent except for one. Usually, the active VSG has been recently duplicated and translocated to one of about 20 potential bloodstream VSG expression sites (B-ESs). Each of the 20 potential B-ESs is adjacent to a chromosomal telomere, but only one B-ES is actively transcribed in a given organism. Recent evidence suggests the active B-ES is situated in an extra-nucleolar body of the nucleus where it is transcribed by RNA polymerase I. Members of another group of about 20 telomere-linked VSG expression sites (the M-ESs) are expressed only during the metacyclic stage of the parasite in its tsetse fly vector. Progress in sequencing the African trypanosome genome has led to additional insights on the organization of genes within both groups of ESs that may ultimately suggest better ways to control or eliminate this deadly pathogen.

摘要

非洲锥虫是原生动物寄生虫,寄生于哺乳动物的血液中,在那里它们不断面临针对它们的免疫反应。它们通过不断地从表面一种可变表面糖蛋白(VSG)的表达转换为另一种免疫上不同的VSG的表达,从而在免疫系统面前始终领先一步——这种现象称为抗原变异。大约1000个VSG基因(VSGs)和假VSGs分散在整个锥虫基因组中,除了一个之外,所有这些基因在转录上都是沉默的。通常,活跃的VSG最近被复制并转移到大约20个潜在的血液中VSG表达位点(B-ESs)之一。20个潜在的B-ESs中的每一个都与染色体端粒相邻,但在给定的生物体中只有一个B-ES被积极转录。最近的证据表明,活跃的B-ES位于细胞核的一个核仁外体中,在那里它由RNA聚合酶I转录。另一组大约20个与端粒相连的VSG表达位点(M-ESs)的成员仅在寄生虫在采采蝇载体中的循环后期阶段表达。非洲锥虫基因组测序的进展导致了对两组ESs内基因组织的更多见解,这最终可能会提出更好的控制或消除这种致命病原体的方法。

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