Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure.
Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure.
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DOI：
10.1101/gr.6421207
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发表时间：
2007-09
期刊：
影响因子：
7
通讯作者：
Barry, J David
中科院分区：
文献类型：
--
作者：
Marcello, Lucio;Barry, J David
布氏锥虫通过其大量沉默变异表面糖蛋白（VSG）基因的差异激活来逃避宿主获得性免疫，其中大部分是亚端粒阵列中的假基因。我们分析了 940 个 VSG，占阵列的二分之一到三分之二。确认了 VSG N 端结构域的序列类型 A 和 B，而发现 C 型是 A 型的组成部分。发现了两种新的 C 端结构域类型。几乎所有域类型的组合都发生了，但对特定组合存在一些偏差。编码的 N 端结构域的三分之一（但只有 13% 的 C 端结构域）是完整的，表明沉默 VSG 特别需要获得要表达的功能性 C 端结构域。大约 60% 的 VSG 是独特的，其余的出现在 2-4 个密切同源物的亚家族中（>50-52% 肽同一性）。我们发现了 VSG 相关基因的子集，其基因组环境和表达模式与 VSG 不同，并预测它们具有不同的功能。几乎所有（92%）全长阵列 VSG 都具有与激活沉默基因的复制机制相关的部分保守侧翼，这些序列也有助于档案进化，介导阵列内和阵列之间包含 ≥ 1 VSG 的大部分片段转换。在感染过程中，完整的阵列基因在 2 周后通过复制而被激活，由假基因组装的嵌合 VSG 在第 3 周开始表达，并在第 4 周占主导地位。档案的小亚科结构似乎对于为嵌合体形成提供相互作用的供体至关重要。
Trypanosoma brucei evades host acquired immunity through differential activation of its large archive of silent variant surface glycoprotein (VSG) genes, most of which are pseudogenes in subtelomeric arrays. We have analysed 940 VSGs, representing one half to two thirds of the arrays. Sequence types A and B of the VSG N-terminal domains were confirmed, while type C was found to be a constituent of type A. Two new C-terminal domain types were found. Nearly all combinations of domain types occurred, with some bias to particular combinations. One-third of encoded N-terminal domains, but only 13% of C-terminal domains, are intact, indicating a particular need for silent VSGs to gain a functional C-terminal domain to be expressed. About 60% of VSGs are unique, the rest occurring in subfamilies of 2-4 close homologues (>50-52% peptide identity). We found a subset of VSG-related genes, differing from VSGs in genomic environment and expression patterns, and predict they have distinct function. Almost all (92%) full-length array VSGs have the partially conserved flanks associated with the duplication mechanism that activates silent genes, and these sequences have also contributed to archive evolution, mediating most of the conversions of segments, containing ≥ 1 VSG, within and between arrays. During infection, intact array genes became activated by duplication after 2 weeks, and mosaic VSGs assembled from pseudogenes became expressed by week 3 and predominated by week 4. The small subfamily structure of the archive appears to be fundamental in providing the interacting donors for mosaic formation.