组成型外显子在进化过程中的选择
The Alternative Choice of Constitutive Exons throughout Evolution
摘要：
已知替代盒外显子起源于内含子序列的外显子化和外显子改组两个过程。在此，我们提出了一个额外的机制，组成型剪接外显子成为替代盒外显子在进化过程中。我们编译了一个来自人类和小鼠的正向外显子数据集，这些外显子在一个物种中组成性剪接，但在另一个物种中选择性剪接。这些外显子的检查表明，共同的祖先组成性剪接。我们表明，在进化过程中的59剪接位点的松弛是外显子从组成型转变为可变剪接的分子机制之一。这种转变与外显子剪接调控序列（ESR）的固定有关，这些序列对外显子定义至关重要，并且仅在过渡到可变剪接后才控制包含水平。从鱼类到人类，每个ESR对剪接的影响和两个ESR之间的组合效应是保守的。我们的研究结果揭示了一个进化途径，通过将外显子从组成型剪接转移到可变剪接来增加转录组多样性
英文摘要：
Alternative cassette exons are known to originate from two processes exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exons suggests that the common ancestors were constitutively spliced. We show that relaxation of the 59 splice site during evolution is one of the molecular mechanisms by which exons shift from constitutive to alternative splicing. This shift is associated with the fixation of exonic splicing regulatory sequences (ESRs) that are essential for exon definition and control the inclusion level only after the transition to alternative splicing. The effect of each ESR on splicing and the combinatorial effects between two ESRs are conserved from fish to human. Our results uncover an evolutionary pathway that increases transcriptome diversity by shifting exons from constitutive to alternative splicing
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