The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense.

The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense.
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DOI:
10.1093/gbe/evy186
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发表时间:
2018-09-01
影响因子:
3.3
通讯作者:
Jackson AP
Jackson AP
中科院分区:
生物学2区
文献类型:
--
作者:
Abbas AH;Silva Pereira S;D'Archivio S;Wickstead B;Morrison LJ;Hall N;Hertz-Fowler C;Darby AC;Jackson AP

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非洲锥虫病是一种由非洲锥虫(锥虫属)引起的人类和牲畜病媒传播疾病。在脊椎动物血流中的存活取决于寄生虫表面包被的变异表面糖蛋白(VSG)的抗原变异。于T.布鲁氏菌,抗原变异的模型,单等位基因VSG表达起源于专用的VSG表达位点(VES)。布氏锥虫VES具有由独特的重复序列下游的端粒VSG位点和独立的启动子组成的保守结构。另外的蛋白质编码序列,被称为“表达位点相关基因(ESAG)”,也经常存在,并涉及不同的血流阶段功能。刚果锥虫是一种相关的兽医病原体,也显示VSG介导的抗原变异。霸王刚果VES尚未被描述,使得不清楚VSG表达的调节在物种之间是否是保守的。在这里,我们描述了一个保守的端粒区与VSG基因座从长读DNA测序的两个T。congolense菌株,它由一个远端重复序列,保守的非编码元件和其他基因除了VSG;虽然这些不是直向的T.布鲁氏菌ESAGs。大多数保守的端粒区域与附属的微小染色体有关,但同样的结构也可能与巨大染色体有关。我们认为该区域代表T. Congolense VES,并与T.布氏锥虫,我们讨论了抗原转换机制的平行进化,和独特的适应T。布鲁氏菌VES用于血流阶段基因的发育调节。因此,我们为理解T.刚果和非洲锥虫VES的起源。
African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as “Expression Site Associated Genes (ESAGs)”, are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.
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期刊: Nature reviews. Microbiology
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