Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes
Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes
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DOI：
10.1101/gr.6818908
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发表时间：
2008-01-01
期刊：
影响因子：
7
通讯作者：
Ast, Gil
中科院分区：
文献类型：
--
作者：
Schwartz, Schraga H.;Silva, Joao;Ast, Gil
内含子是真核生物基因的标志之一。内含子的剪接由三个主要剪接信号指导：5'剪接位点（5' ss）、分支位点（BS）和多聚嘧啶段/3 '剪接位点（PPT-3' ss）。为了研究这些剪接信号的进化，我们对来自22种真核生物的120多万个内含子中的这些信号进行了系统的比较分析。我们的分析表明，所有这些信号都发生了戏剧性的进化：PPT在大多数真菌中很弱，在植物和原生动物中居中，在后生动物中最强。在后生动物中，从秀丽隐杆线虫到人类，它逐渐加强。5 'ss和BS在大多数生物中是简并的，但在一些真菌中高度保守。最大简约为基础的算法重建祖先的位置特异性评分矩阵表明，祖先的5 'SS和BS退化，在后生动物。为了阐明剪接信号的进化变异，我们分析了结合这些信号的因子的进化变化。我们的分析揭示了剪接信号及其相应的剪接因子的共同进化：PPT的强度与其相应的剪接因子U2 AF 2中关键残基的变化相关;在5 'ss和结合它的Ul snRNA的变化之间发现了有限的相关性;但在BS和U2 snRNA之间没有发现。因此，尽管真核生物剪接内含子的基本能力在整个进化过程中保持保守，但剪接信号及其相应的剪接因子已经发生了相当大的进化，独特地塑造了不同生物的剪接机制。
Introns are among the hallmarks of eukaryotic genes. Splicing of introns is directed by three main splicing signals: the 5' splice site (5'ss), the branch site (BS), and the polypyrimdine tract/3'splice site (PPT-3'ss). To Study the evolution of these splicing signals, we have conducted a systematic comparative analysis of these signals in over 1.2 million introns from 22 eukaryotes. our analyses suggest that all these signals have dramatically evolved: The PPT is weak among most fungi, intermediate in plants and protozoans, and strongest in metazoans. Within metazoans it shows a gradual strengthening from Caenorhabditis elegans to human. The 5'ss and the BS were found to be degenerate among most organisms, but highly conserved among some fungi. A maximum parsimony-based algorithm for reconstructing ancestral position-specific scoring matrices suggested that the ancestral 5'ss and BS were degenerate, as in metazoans. To shed light on the evolutionary variation in splicing signals, we have analyzed the evolutionary changes in the factors that bind these signals. Our analysis reveals coevolution of splicing signals and their corresponding splicing factors: The strength of the PPT is correlated to changes in key residues in its corresponding splicing factor U2AF2; limited correlation was found between changes in the 5'ss and Ul snRNA that binds it; but not between the BS and U2 snRNA. Thus, although the basic ability of eukaryotes to splice introns has remained conserved throughout evolution, the splicing signals and their corresponding splicing factors have considerably evolved, uniquely shaping the splicing mechanisms of different organisms.