Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomes
Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomes
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DOI：
10.1261/rna.325107
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发表时间：
2007-05-01
期刊：
影响因子：
4.5
通讯作者：
Lee, Christopher J.
中科院分区：
文献类型：
--
作者：
Alekseyenko, Alexander V.;Kim, Namshin;Lee, Christopher J.
选择性剪接（AS）与外显子加速进化的关系最近引起了人们对其在真核生物基因结构进化中的作用的广泛关注。以前的研究仅限于小鼠和/或人类的外显子产生或丢失事件的分析。我们的多基因组方法提供了一种方法：(1)在大范围内区分创造和损失事件；(2)揭示相关进化机制的细节；(3)在广泛的进化时间和有机体范围内估算相应的速率；(4)评估AS对这些进化速率的影响。我们使用先前未发表的对ASAP数据库中5个物种（人类、小鼠、狗、牛和斑马鱼）的选择性剪接的独立分析，结合对17个基因组的全基因组多重比对，来分析哺乳动物、鱼类和鸟类的组成性和选择性剪接外显子的产生和丢失。我们的分析提供了一个关于3.6亿年脊椎动物进化中外显子产生和丢失事件的综合数据库，包括成千上万的替代外显子和组成外显子。我们发现外显子包含水平与外显子生成速率成反比。此外，我们对外显子产生和丢失的机制进行了详细深入的分析，这表明大部分非重复外显子是由纯内含子序列从头开始产生的结果。我们的数据表明，选择性剪接在新外显子的产生中起着重要作用，并为未来基因组进化研究提供了有用的新数据库资源。
Association of alternative splicing ( AS) with accelerated rates of exon evolution in some organisms has recently aroused widespread interest in its role in evolution of eukaryotic gene structure. Previous studies were limited to analysis of exon creation or lost events in mouse and/or human only. Our multigenome approach provides a way for ( 1) distinguishing creation and loss events on the large scale; ( 2) uncovering details of the evolutionary mechanisms involved; ( 3) estimating the corresponding rates over a wide range of evolutionary times and organisms; and ( 4) assessing the impact of AS on those evolutionary rates. We use previously unpublished independent analyses of alternative splicing in five species ( human, mouse, dog, cow, and zebrafish) from the ASAP database combined with genomewide multiple alignment of 17 genomes to analyze exon creation and loss of both constitutively and alternatively spliced exons in mammals, fish, and birds. Our analysis provides a comprehensive database of exon creation and loss events over 360 million years of vertebrate evolution, including tens of thousands of alternative and constitutive exons. We find that exon inclusion level is inversely related to the rate of exon creation. In addition, we provide a detailed in-depth analysis of mechanisms of exon creation and loss, which suggests that a large fraction of nonrepetitive created exons are results of ab initio creation from purely intronic sequences. Our data indicate an important role for alternative splicing in creation of new exons and provide a useful novel database resource for future genome evolution research.