Evolution of Characterized Phosphorylation Sites in Budding Yeast
Evolution of Characterized Phosphorylation Sites in Budding Yeast
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DOI：
10.1093/molbev/msq090
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发表时间：
2010-09-01
影响因子：
10.7
通讯作者：
Moses, Alan M.
中科院分区：
文献类型：
--
作者：
Ba, Alex N. Nguyen;Moses, Alan M.
磷酸化是真核细胞中研究最多和最重要的调节蛋白质功能的机制之一。最近，一些研究已经调查了高通量方法鉴定的磷酸化位点的演变。这些研究揭示了不同程度的限制和可塑性的证据，因此，目前还没有共识，这一重要的调节机制的进化特性。在这里，我们提出了一个高置信度的注释网站从芽殖酵母的研究，并表明，这些网站是显着的限制相比，其侧翼区在密切相关的物种。我们表明，这种属性不会改变结构化或非结构化区域。我们研究了磷酸化位点的产生、死亡和补偿率，并测试了在具有更多位点的蛋白质中，位点是否更容易获得或失去。最后，我们还表明，这种进化的保守性可以产生显着改善激酶靶预测时，激酶识别基序是已知的，并可以用来推断识别基序时，一组目标是已知的。我们的分析表明，磷酸化位点的选择性约束下，符合其功能的重要性。我们还发现，在进化过程中，一小部分的磷酸化位点的周转，这可能是一个重要的过程中的调控网络的进化。
Phosphorylation is one of the most studied and important regulatory mechanisms that modulate protein function in eukaryotic cells. Recently, several studies have investigated the evolution of phosphorylation sites identified by high-throughput methods. These studies have revealed varying degrees of evidence for constraint and plasticity, and therefore, there is currently no consensus as to the evolutionary properties of this important regulatory mechanism. Here, we present a study of high-confidence annotated sites from budding yeast and show that these sites are significantly constrained compared with their flanking region in closely related species. We show that this property does not change in structured or unstructured regions. We investigate the birth, death and compensation rates of the phosphorylation sites and test if sites are more likely to be gained or lost in proteins with greater numbers of sites. Finally, we also show that this evolutionary conservation can yield significant improvement for kinase target predictions when the kinase recognition motif is known, and can be used to infer the recognition motif when a set of targets is known. Our analysis indicates that phosphorylation sites are under selective constraint, consistent with their functional importance. We also find that a small fraction of phosphorylation sites turnover during evolution, which may be an important process underlying the evolution of regulatory networks.