The VEXing problem of monoallelic expression in the African trypanosome.
The VEXing problem of monoallelic expression in the African trypanosome.
复制标题
非洲锥虫中单等位基因表达的令人烦恼的问题。
DOI：
10.1073/pnas.1608546113
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发表时间：
2016
影响因子：
11.1
通讯作者：
Papavasiliou,FNina
中科院分区：
文献类型：
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作者：
Schulz,Danae;Papavasiliou,FNina
非洲布鲁氏锥虫是非洲锥虫病（在人类中也称为“昏睡病”，在牛中称为“那迦纳病”）的病原体，给撒哈拉以南非洲地区造成巨大的经济负担。布氏体病通过采采蝇的叮咬传播给哺乳动物宿主。在哺乳动物中，它在细胞外的血液中存活，最终迁移到中枢神经系统，导致昏迷和死亡。为了在哺乳动物宿主的血液中存活，布鲁氏杆菌必须避开宿主的免疫系统。寄生虫被一层致密的变异表面糖蛋白（VSG）外壳覆盖，该外壳保护细胞表面的其他表位免受宿主免疫系统产生的抗体的侵害。1和2)。当寄生虫进入血液时，对VSG产生强烈的抗体反应。然而，这种寄生虫携带着数千种VSG基因的变体，并周期性地切换在一种称为抗原变异的过程中表达的特定变体（在布鲁氏体中俗称为“切换”）(1)。VSG基因是从~ 15个端粒血流表达位点（BESs）中的一个转录的，在任何给定时间只有一个是转录活性的。VSG基因的转录发生在一个称为表达位点体（ESB）的离散核结构中，并由Pol I(1)驱动。从一个VSG到一个新的VSG的表达转换可以通过多种机制发生，包括新的BES的转录激活和重组机制(1)。对感染小鼠模型中的布氏体种群的分析表明，一个锥虫种群可以在任何给定时间内含有表达多达66种不同VSGs的寄生虫(3)。然而，尽管在锥虫群体中表达的VSG种类相当多样，但在任何给定时间，单个锥虫在其表面只表达一个VSG，除非主动进行转换。在不同的生物系统中发现了单基因变异的单等位基因表达，包括Ig基因的等位基因排斥、嗅觉受体表达、视网膜中视紫红质基因的使用和x染色体失活。从而了解单等位基因的调控
The African trypanosome, Trypanosoma brucei, is a causative agent of African Trypanosomiasis (also known as “sleeping sickness” in humans and “nagana” in cattle) and imposes an enormous economic burden in regions of Sub-Saharan Africa. T. brucei is transmitted to the mammalian host through the bite of the tsetse fly. In the mammal, it survives extracellularly in the bloodstream, eventually migrating into the central nervous system and causing coma and death. To survive in the bloodstream of its mammalian host, T. brucei must evade the host immune system. The parasite is covered by a dense, variant surface glycoprotein (VSG) coat that shields other epitopes on the cell surface from antibodies produced by the host immune system (reviewed in refs. 1 and 2). A strong antibody response is mounted against the VSG upon entry of the parasite into the bloodstream. However, the parasite harbors thousands of variants of the VSG gene and periodically switches the particular variant that is expressed in a process called antigenic variation (known colloquially in T. brucei as “switching”)(1).VSG genes are transcribed from one of∼ 15 telomeric bloodstream expression sites (BESs), only one of which is transcriptionally active at any given time. Transcription of VSG genes occurs within a discrete nuclear structure, called the expression site body (ESB) and is driven by Pol I (1). Switching from expression of one VSG to a new VSG can occur by multiple mechanisms, including transcriptional activation of a new BES and recombinatorial mechanisms (1). Analysis of T. brucei populations in mouse models of infection has revealed that a population of trypanosomes can contain parasites expressing as many as 66 different VSGs at any given time (3). However, although the repertoire of VSGs expressed in a population of trypanosomes is quite diverse, a single trypanosome expresses just one VSG on its surface at any given time, except when actively undergoing a switch. Monoallelic expression of a single gene variant is found across diverse biological systems, including allelic exclusion of Ig genes, olfactory receptor expression, rhodopsin gene use in the retina, and X-chromosome inactivation. Thus, understanding the regulation of monoallelic