Short linear motifs - ex nihilo evolution of protein regulation.
Short linear motifs - ex nihilo evolution of protein regulation.
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DOI：
10.1186/s12964-015-0120-z
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发表时间：
2015-11-21
期刊：
影响因子：
--
通讯作者：
Moses AM
中科院分区：
文献类型：
--
作者：
Davey NE;Cyert MS;Moses AM
短序列基序普遍存在于三种主要类型的生物分子中：数百类和数千种DNA调控元件，RNA基序和蛋白质短线性基序（SLiM）已被表征。高等真核生物中转录、转录后和翻译后调控复杂性的增加与基序使用的显著扩展相吻合。但真核细胞是如何获得如此庞大的基序库的呢？在这篇综述中，我们整理了有关蛋白质基序进化的现有文献，并讨论了表明SLiMs可以通过无序区域的突变、插入和缺失获得的证据。我们提出了一种机制的exnihilo SLiM进化-一个新的SLiM的进化从“没有”-添加一个功能模块到以前的非功能区的蛋白质序列。在我们的模型中，高等真核生物蛋白质中的数百个基序结合结构域将简单的基序特异性与有用的功能连接起来，以创建一个大的功能基序空间。与这些基序结合结构域的特异性相匹配的可变肽不断地被快速进化的无序区域中的突变产生和破坏，从而产生可能具有有利的表型新奇的新相互作用的动态供应。这提供了一个多样性库来修改现有的交互网络。进化的压力将作用于这些图案，以保留有益的实例。然而，大多数将失去一个进化的时间尺度上的负选择和遗传漂变作用于有害和中性图案分别。鉴于所提出的模型与基因和（前）mRNA的调控片段中的基序进化之间的相似之处，我们建议我们对调控网络的理解将受益于创建一个描述转录、转录后和翻译后调控进化的共享模型。
Short sequence motifs are ubiquitous across the three major types of biomolecules: hundreds of classes and thousands of instances of DNA regulatory elements, RNA motifs and protein short linear motifs (SLiMs) have been characterised. The increase in complexity of transcriptional, post-transcriptional and post-translational regulation in higher Eukaryotes has coincided with a significant expansion of motif use. But how did the eukaryotic cell acquire such a vast repertoire of motifs? In this review, we curate the available literature on protein motif evolution and discuss the evidence that suggests SLiMs can be acquired by mutations, insertions and deletions in disordered regions. We propose a mechanism of ex nihilo SLiM evolution – the evolution of a novel SLiM from “nothing” – adding a functional module to a previously non-functional region of protein sequence. In our model, hundreds of motif-binding domains in higher eukaryotic proteins connect simple motif specificities with useful functions to create a large functional motif space. Accessible peptides that match the specificity of these motif-binding domains are continuously created and destroyed by mutations in rapidly evolving disordered regions, creating a dynamic supply of new interactions that may have advantageous phenotypic novelty. This provides a reservoir of diversity to modify existing interaction networks. Evolutionary pressures will act on these motifs to retain beneficial instances. However, most will be lost on an evolutionary timescale as negative selection and genetic drift act on deleterious and neutral motifs respectively. In light of the parallels between the presented model and the evolution of motifs in the regulatory segments of genes and (pre-)mRNAs, we suggest our understanding of regulatory networks would benefit from the creation of a shared model describing the evolution of transcriptional, post-transcriptional and post-translational regulation.
影响因子：
3.4
作者：
Ruths T;Nakhleh L
通讯作者：
Nakhleh L