Exon creation and establishment in human genes.
Exon creation and establishment in human genes.
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DOI：
10.1186/gb-2008-9-9-r141
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发表时间：
2008
期刊：
影响因子：
12.3
通讯作者：
Eyras E
中科院分区：
文献类型：
--
作者：
Corvelo A;Eyras E
选择性剪接外显子的比较基因组学研究显示剪接调控基序的相对局部丰度影响人类的剪接决定。大部分物种特异性外显子是选择性剪接的。在灵长类动物中，Alu元件在外显子产生过程中起着至关重要的作用，但许多新的外显子也是通过其他机制出现的。尽管最近有许多研究，但仍不清楚从头外显子化的剪接调控要求是什么，以及剪接调控在外显子的整个生命周期中如何变化。使用比较基因组学，我们已经定义了不同进化年龄的外显子组。较年轻的外显子有较弱的剪接位点和较低的绝对值之间的外显子和相邻的内含子区域的相对丰度推定的剪接调节，表明一个不太巩固的剪接调节。这种相对丰度显示出随着外显子年龄的增加而增加，导致更高的外显子包含。我们表明，调节因子密度的这种局部差异可能具有生物学意义，因为它在真实的外显子与伪外显子分类中优于其他指标。我们应用这种新的措施的反义Alu元素的外显子化的具体情况下，并表明它们的特点是一般缺乏外显子剪接沉默。我们的研究结果表明，特定的序列环境需要外显化，这些可以随时间而变化。我们提出了一个模型，外显子的创建和建立在人类基因中，剪接决定依赖于相对本地丰富的调控基序。使用这个模型，我们提供了进一步的解释，为什么铝元素作为一个主要的基板在灵长类动物的外显子创建。最后，我们讨论了在基因预测中整合这些信息的好处。
A comparative genomics study of alternatively spliced exons showing that the relative local abundance of splicing regulatory motifs influences splicing decisions in humans. A large proportion of species-specific exons are alternatively spliced. In primates, Alu elements play a crucial role in the process of exon creation but many new exons have appeared through other mechanisms. Despite many recent studies, it is still unclear which are the splicing regulatory requirements for de novo exonization and how splicing regulation changes throughout an exon's lifespan. Using comparative genomics, we have defined sets of exons with different evolutionary ages. Younger exons have weaker splice-sites and lower absolute values for the relative abundance of putative splicing regulators between exonic and adjacent intronic regions, indicating a less consolidated splicing regulation. This relative abundance is shown to increase with exon age, leading to higher exon inclusion. We show that this local difference in the density of regulators might be of biological significance, as it outperforms other measures in real exon versus pseudo-exon classification. We apply this new measure to the specific case of the exonization of anti-sense Alu elements and show that they are characterized by a general lack of exonic splicing silencers. Our results suggest that specific sequence environments are required for exonization and that these can change with time. We propose a model of exon creation and establishment in human genes, in which splicing decisions depend on the relative local abundance of regulatory motifs. Using this model, we provide further explanation as to why Alu elements serve as a major substrate for exon creation in primates. Finally, we discuss the benefits of integrating such information in gene prediction.
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