Identification of novel aspartic proteases from Strongyloides ratti and characterisation of their evolutionary relationships, stage-specific expression and molecular structure.
Identification of novel aspartic proteases from Strongyloides ratti and characterisation of their evolutionary relationships, stage-specific expression and molecular structure.
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DOI：
10.1186/1471-2164-10-611
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发表时间：
2009-12-16
期刊：
影响因子：
4.4
通讯作者：
Paterson S
中科院分区：
文献类型：
--
作者：
Mello LV;O'Meara H;Rigden DJ;Paterson S
天冬氨酸蛋白酶在线虫寄生生物学中起重要作用。这种作用在吸血线虫中表现得最好，在那里它们消化血红蛋白，但它们也可能在不以血液为食的线虫寄生虫的生物学中发挥重要作用。在目前的工作中，我们调查的进化和表达的天冬氨酸蛋白酶类圆线虫，这允许一个独特的比较寄生和自由生活的成人形式在其生命周期。我们确定了8个转录的天冬氨酸蛋白酶序列和另外两个基因组序列，并将其与秀丽隐杆线虫和其他线虫物种的同源物进行了比较。系统发育分析显示了一个复杂的基因进化模式，例如一些S。ratti序列与C.但这两种线虫中的其他天冬氨酸蛋白酶也发生了谱系特异性扩展。这些基因复制事件可能有助于这两个物种适应不同的生活方式。在S. Ratti天冬氨酸蛋白酶是两种密切相关的同种型，其在不同的生命阶段显示出差异表达：ASP-2A在寄生雌性中高度表达，而ASP-2B主要存在于自由生活的成虫中。ASP-2亚型的分子建模显示，它们的底物特异性可能非常相似，但ASP-2B在其整个分子表面上比ASP-2A更具静电负性。这种特性可能与这两种异构体所处环境的不同pH值有关。我们证明了S. ratti提供了一个强有力的模型，以探索与寄生与自由生活的生活方式相关的遗传适应。我们已经发现了天冬氨酸蛋白酶基因的基因重复类圆线虫，并确定了一对旁系同源物的差异表达的寄生或自由生活阶段的线虫的生命周期，符合适应性作用的天冬氨酸蛋白酶在线虫寄生的进化。
Aspartic proteases are known to play an important role in the biology of nematode parasitism. This role is best characterised in blood-feeding nematodes, where they digest haemoglobin, but they are also likely to play important roles in the biology of nematode parasites that do not feed on blood. In the present work, we investigate the evolution and expression of aspartic proteases in Strongyloides ratti, which permits a unique comparison between parasitic and free-living adult forms within its life-cycle. We identified eight transcribed aspartic protease sequences and a further two genomic sequences and compared these to homologues in Caenorhabditis elegans and other nematode species. Phylogenetic analysis demonstrated a complex pattern of gene evolution, such that some S. ratti sequences had a one-to-one correspondence with orthologues of C. elegans but that lineage-specific expansions have occurred for other aspartic proteases in these two nematodes. These gene duplication events may have contributed to the adaptation of the two species to their different lifestyles. Among the set of S. ratti aspartic proteases were two closely-related isoforms that showed differential expression during different life stages: ASP-2A is highly expressed in parasitic females while ASP-2B is predominantly found in free-living adults. Molecular modelling of the ASP-2 isoforms reveals that their substrate specificities are likely to be very similar, but that ASP-2B is more electrostatically negative over its entire molecular surface than ASP-2A. This characteristic may be related to different pH values of the environments in which these two isoforms operate. We have demonstrated that S. ratti provides a powerful model to explore the genetic adaptations associated with parasitic versus free-living life-styles. We have discovered gene duplication of aspartic protease genes in Strongyloides and identified a pair of paralogues differentially expressed in either the parasitic or the free-living phase of the nematode life-cycle, consistent with an adaptive role for aspartic proteases in the evolution of nematode parasitism.
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影响因子：
14.9
作者：
Ceroni, Alessio;Passerini, Andrea;Vullo, Alessandro;Frasconi, Paolo
通讯作者：
Frasconi, Paolo
影响因子：
2.1
作者：
MCKERROW, JH;BRINDLEY, P;NEVA, FA
通讯作者：
NEVA, FA
影响因子：
5.6
作者：
Jones, DT
通讯作者：
Jones, DT
DOI：
10.1107/s0907444904026460
发表时间：
2004-12-01
影响因子：
2.2
作者：
Krissinel, E;Henrick, K
通讯作者：
Henrick, K
影响因子：
4
作者：
Evans, Helen;Mello, Luciane V.;Paterson, Steve
通讯作者：
Paterson, Steve