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密集系统发育树中模块化蛋白质进化的定量与功能分析

Quantification and functional analysis of modular protein evolution in a dense phylogenetic tree.

作者信息

Moore Andrew D, Grath Sonja, Schüler Andreas, Huylmans Ann K, Bornberg-Bauer Erich

机构信息

Institute for Evolution and Biodiversity, Münster, Germany.

出版信息

Biochim Biophys Acta. 2013 May;1834(5):898-907. doi: 10.1016/j.bbapap.2013.01.007. Epub 2013 Feb 1.

DOI:10.1016/j.bbapap.2013.01.007
PMID:23376183
Abstract

Modularity is a hallmark of molecular evolution. Whether considering gene regulation, the components of metabolic pathways or signaling cascades, the ability to reuse autonomous modules in different molecular contexts can expedite evolutionary innovation. Similarly, protein domains are the modules of proteins, and modular domain rearrangements can create diversity with seemingly few operations in turn allowing for swift changes to an organism's functional repertoire. Here, we assess the patterns and functional effects of modular rearrangements at high resolution. Using a well resolved and diverse group of pancrustaceans, we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss. Our results show that roughly 16 new arrangements arise per million years and that between 64% and 81% of these can be explained by simple, single-step modular rearrangement events. We find evidence that the frequencies of fission and terminal deletion events increase over time, and that modular rearrangements impact all levels of the cellular signaling apparatus and thus may have strong adaptive potential. Novel arrangements that cannot be explained by simple modular rearrangements contain a significant amount of repeat domains that occur in complex patterns which we term "supra-repeats". Furthermore, these arrangements are significantly longer than those with a single-step rearrangement solution, suggesting that such arrangements may result from multi-step events. In summary, our analysis provides an integrated view and initial quantification of the patterns and functional impact of modular protein evolution in a well resolved phylogenetic tree. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.

摘要

模块化是分子进化的一个标志。无论是考虑基因调控、代谢途径的组成部分还是信号级联反应,在不同分子环境中重用自主模块的能力都可以加速进化创新。同样,蛋白质结构域是蛋白质的模块,模块化的结构域重排可以通过看似很少的操作创造多样性,进而使生物体的功能库能够迅速发生变化。在这里,我们以高分辨率评估模块化重排的模式和功能影响。我们使用一组分类明确且多样的泛甲壳动物,展示了亲缘关系密切的生物体内部的排列多样性,估计了排列更替频率,并首次建立了融合、裂变、结构域添加和末端缺失的分支特异性速率估计值。我们的结果表明,每百万年大约会出现16种新的排列,其中64%到81%可以由简单的单步模块化重排事件来解释。我们发现有证据表明,裂变和末端缺失事件的频率会随着时间增加,并且模块化重排会影响细胞信号传导装置的各个层面,因此可能具有很强的适应潜力。无法用简单的模块化重排来解释的新排列包含大量以复杂模式出现的重复结构域,我们将其称为“超重复序列”。此外,这些排列明显长于具有单步重排解决方案的排列,这表明此类排列可能是多步事件的结果。总之,我们的分析提供了一个综合观点,并对在一个分类明确的系统发育树中模块化蛋白质进化的模式和功能影响进行了初步量化。本文是名为:蛋白质的新兴动态观点:变构、进化和自组装中的蛋白质可塑性的特刊的一部分。

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