Modeling the evolution dynamics of exon-intron structure with a general random fragmentation process.
Modeling the evolution dynamics of exon-intron structure with a general random fragmentation process.
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DOI：
10.1186/1471-2148-13-57
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发表时间：
2013-02-28
影响因子：
3.4
通讯作者：
Stein LD
中科院分区：
文献类型：
--
作者：
Wang L;Stein LD
大多数真核基因都被剪接体内含子打断。尽管基因组测序技术发展迅速，但外显子-内含子结构的进化仍然是个谜。在这项工作中，我们采用了一种新的方法，假设外显子-内含子结构的演化是一个随机过程，并且这个过程的特征可以通过考察它的历史结果--内部翻译外显子(Exon)的今天大小分布来理解。通过模拟和模拟外显子在不同物种中的大小分布，我们提出了一个通用随机碎裂过程(GRFP)来表征外显子-内含子结构的进化动力学。该模型准确地预测了外显子被新内含子分裂的概率以及新插入片段在外显子长度上的分布。作为该模型的第一个观察结果，我们表明外显子获得内含子的机会与其大小成正比。我们还表明，这种大小依赖关系在基因中几乎是恒定的，除了与5‘非编码区相邻的外显子。作为模型的第二个结论，我们发现内含子插入位点服从正态分布，平均值为0.5(外显子中心)，标准差为0.11。最后，我们证明了基因内含子的插入对于脊椎动物来说是相互独立的，但对于非脊椎动物来说是更负相关的。我们使用模拟来证明这种负相关性可能是由于进化过程中显著的内含子丢失造成的，这可以通过对这些生物中的多内含子基因的选择来解释。GRFP模型表明，内含子的增长是动态的，外显子较长的几率较高；内含子随机插入外显子，概率最高的是外显子的中心。GRFP估计，脊椎动物基因组每10kb的编码序列中有78个内含子，这与经验观察一致。GRFP还估计，在非脊椎动物基因组的进化过程中存在显著的内含子丢失，极端情况下，黑腹果蝇的内含子丢失约57%，秀丽线虫的内含子丢失约28%，水稻约24%。
Most eukaryotic genes are interrupted by spliceosomal introns. The evolution of exon-intron structure remains mysterious despite rapid advance in genome sequencing technique. In this work, a novel approach is taken based on the assumptions that the evolution of exon-intron structure is a stochastic process, and that the characteristics of this process can be understood by examining its historical outcome, the present-day size distribution of internal translated exons (exon). Through the combination of simulation and modeling the size distribution of exons in different species, we propose a general random fragmentation process (GRFP) to characterize the evolution dynamics of exon-intron structure. This model accurately predicts the probability that an exon will be split by a new intron and the distribution of novel insertions along the length of the exon. As the first observation from this model, we show that the chance for an exon to obtain an intron is proportional to its size to the 3rd power. We also show that such size dependence is nearly constant across gene, with the exception of the exons adjacent to the 5′ UTR. As the second conclusion from the model, we show that intron insertion loci follow a normal distribution with a mean of 0.5 (center of the exon) and a standard deviation of 0.11. Finally, we show that intron insertions within a gene are independent of each other for vertebrates, but are more negatively correlated for non-vertebrate. We use simulation to demonstrate that the negative correlation might result from significant intron loss during evolution, which could be explained by selection against multi-intron genes in these organisms. The GRFP model suggests that intron gain is dynamic with a higher chance for longer exons; introns are inserted into exons randomly with the highest probability at the center of the exon. GRFP estimates that there are 78 introns in every 10 kb coding sequences for vertebrate genomes, agreeing with empirical observations. GRFP also estimates that there are significant intron losses in the evolution of non-vertebrate genomes, with extreme cases of around 57% intron loss in Drosophila melanogaster, 28% in Caenorhabditis elegans, and 24% in Oryza sativa.
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