Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss
Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss
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DOI：
10.1038/ng1159
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发表时间：
2003-06-01
期刊：
影响因子：
30.8
通讯作者：
Lee, CJ
中科院分区：
文献类型：
--
作者：
Modrek, B;Lee, CJ
比较基因组学中最有趣的机会之一是不仅比较基因组序列，还比较其他现象，例如选择性剪接，使用不同基因组中的正交基因来发现生物体之间的相似性和差异性（1，2）。最近，基因组学研究表明，40-60%的人类基因是选择性剪接的（3-8），并在人类基因中编目了多达30，000种选择性剪接关系（9）。在这里，我们报告了人类和小鼠中9，434个正向剪接基因的分析，这表明选择性剪接与最近外显子创建和/或丢失频率的大幅增加有关。尽管小鼠和人类基因组中的大多数外显子在两种基因组中都是高度保守的，但仅包括在选择性剪接形式（与组成型或主要转录物形式相反）中的外显子大多不保守，因此是最近外显子产生或丢失事件的产物。在大鼠和人类中的正向外显子的类似比较证实了这一模式。虽然这并没有说明适应性益处的复杂问题，但它确实表明这些基因组中的选择性剪接与进化变化的增加有关。
One of the most interesting opportunities in comparative genomics is to compare not only genome sequences but additional phenomena, such as alternative splicing, using orthologous genes in different genomes to find similarities and differences between organisms(1,2). Recently, genomics studies have suggested that 40-60% of human genes are alternatively spliced(3-8) and have catalogued up to 30,000 alternative splice relationships in human genes(9). Here we report an analysis of 9,434 orthologous genes in human and mouse, which indicates that alternative splicing is associated with a large increase in frequency of recent exon creation and/or loss. Whereas most exons in the mouse and human genomes are strongly conserved in both genomes, exons that are only included in alternative splice forms (as opposed to the constitutive or major transcript form) are mostly not conserved and thus are the product of recent exon creation or loss events. A similar comparison of orthologous exons in rat and human validates this pattern. Although this says nothing about the complex question of adaptive benefit, it does indicate that alternative splicing in these genomes has been associated with increased evolutionary change.