Alternatively and constitutively spliced exons are subject to different evolutionary forces
Alternatively and constitutively spliced exons are subject to different evolutionary forces
复制标题
DOI：
10.1093/molbev/msj081
复制
发表时间：
2006-03-01
影响因子：
10.7
通讯作者：
Chuang, TJ
中科院分区：
文献类型：
--
作者：
Chen, FC;Wang, SS;Chuang, TJ
选择性剪接外显子（ASEs）是否比组成性剪接外显子（CSEs）进化得更快一直存在争议。虽然已经注意到ASES比CSE受到更弱的选择性约束，因此它们进化得更快，但也有研究表明ASES的进化速度比CSE慢。在这项研究中，我们检索了5,000多个人-小鼠的正向外显子，并计算了这些外显子中的同义（K-S）和非同义（K-A）替换率。我们的研究结果表明，ASEs具有较高的K-A值和较高的K-A/K-S比值比CSE，表明更快的氨基酸水平的进化在ASEs。更快的进化可能部分是由于较弱的选择性约束。也有可能，更快的速率部分是由于ASEs中更快的功能进化。另一方面，大多数ASE的K-S值低于CSE。参照内含子中的替换率，我们发现ASEs中的K-S值接近中性替换率，而CSE中的同义替换率可能被加速。CSE中同义率的升高与CpG二核苷酸或蛋白质的低复杂性区域无关，但可能与密码子使用偏好性弱相关。在人-大鼠和小鼠-大鼠比较中，也观察到ASE中K-A高于CSE和K-S低于CSE的总体趋势。因此，我们的观察适用于不同分子钟的哺乳动物。
There has been a controversy on whether alternatively spliced exons (ASEs) evolve faster than constitutively spliced exons (CSEs). Although it has been noted that ASEs are subject to weaker selective constraints than CSEs, so they evolve faster, there have also been studies that indicated slower evolution in ASEs than in CSEs. In this study, we retrieve more than 5,000 human-mouse orthologous exons and calculate the synonymous (K-S) and nonsynonymous (K-A) substitution rates in these exons. Our results show that ASEs have higher K-A values and higher K-A/K-S ratios than CSEs, indicating faster amino acid-level evolution in ASEs. The faster evolution may be in part due to weaker selective constraints. It is also possible that the faster rate is in part due to faster functional evolution in ASEs. On the other hand, the majority of ASEs have lower K-S values than CSEs. With reference to the Substitution rate in introns, we show that the K-S values in ASEs are close to the neutral substitution rate, whereas the synonymous substitution rate in CSEs has likely been accelerated. The elevated synonymous rate in CSEs is not related to CpG dinucleotides or low-complexity regions of protein but may be weakly related to codon usage bias. The overall trends of higher K-A and lower K-S in ASEs than in CSEs are also observed in human-rat and mouse-rat comparisons. Therefore, our observations hold for mammals of different molecular clocks.