Molecular determinants and evolutionary dynamics of wobble splicing.
Molecular determinants and evolutionary dynamics of wobble splicing.
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摆动剪接的分子决定因素和进化动力学。
DOI：
10.1093/molbev/msp023
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发表时间：
2009-05
影响因子：
10.7
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Lv J;Yang Y;Yin H;Chu F;Wang H;Zhang W;Zhang Y;Jin Y
串联剪接位点处的选择性剪接(摆动剪接)在许多物种中广泛存在，但指定串联位点的机制仍然知之甚少。在这里，我们使用synaptopagmin I作为模型来分析跨越300多个我的昆虫进化的摆动剪接的系统发育。系统发育分析表明，物种特异性摆动剪接的发生与串联剪接位点处的同义变异有关。进一步的诱变实验表明，由于剪接受体位点的破坏，人为诱导的同义点突变可能会导致摆动剪接丢失。相比之下，在体内剪接实验中，通过人工同义突变模仿祖先串联受体，不能正确地恢复摆动剪接，这表明人工串联剪接位点可能与正常的摆动剪接不相容。此外，结合比较基因组学和杂交微基因分析表明，由于顺式元件序列从3‘端剪接位点进化到5’端剪接位点，库蚊的选择性剪接已经从3‘串联供体进化到5’串联受体。这些数据共同表明，串联剪接位点的选择可能不仅仅是历史的偶然，而在很大程度上是剪接位点和顺式元件序列之间作为摆动剪接基础的共同进化的结果。提出了摆动剪接的演化模型。
Alternative splicing at tandem splice sites (wobble splicing) is widespread in many species, but the mechanisms specifying the tandem sites remain poorly understood. Here, we used synaptotagmin I as a model to analyze the phylogeny of wobble splicing spanning more than 300 My of insect evolution. Phylogenetic analysis indicated that the occurrence of species-specific wobble splicing was related to synonymous variation at tandem splice sites. Further mutagenesis experiments demonstrated that wobble splicing could be lost by artificially induced synonymous point mutations due to destruction of splice acceptor sites. In contrast, wobble splicing could not be correctly restored through mimicking an ancestral tandem acceptor by artificial synonymous mutation in in vivo splicing assays, which suggests that artificial tandem splice sites might be incompatible with normal wobble splicing. Moreover, combining comparative genomics with hybrid minigene analysis revealed that alternative splicing has evolved from the 3′ tandem donor to the 5′ tandem acceptor in Culex pipiens, as a result of an evolutionary shift of cis element sequences from 3′ to 5′ splice sites. These data collectively suggest that the selection of tandem splice sites might not simply be an accident of history but rather in large part the result of coevolution between splice site and cis element sequences as a basis for wobble splicing. An evolutionary model of wobble splicing is proposed.
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影响因子：
64.8
作者：
Clark, Andrew G.;Eisen, Michael B.;MacCallum, Iain
通讯作者：
MacCallum, Iain
影响因子：
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Craxton, M
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Craxton, M
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GEPPERT, M;GODA, Y;SUDHOF, TC
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SUDHOF, TC
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Hu, CA;Lin, WW;Valle, D
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Valle, D
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Koren, Eli;Lev-Maor, Galit;Ast, Gil
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