Expression level, evolutionary rate, and the cost of expression.
Expression level, evolutionary rate, and the cost of expression.
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表达水平、进化速率和表达成本。
DOI：
10.1093/gbe/evq059
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发表时间：
2010
影响因子：
3.3
通讯作者：
Cherry JL
中科院分区：
文献类型：
--
作者：
Cherry JL
由同一基因组编码的蛋白质之间的序列进化速率存在很大差异。与进化速率最密切相关的是表达水平：高表达的蛋白质往往进化缓慢。这一观察结果导致了这样的建议，即蛋白质进化速率的一个主要决定因素涉及由于转录和翻译错误而错误折叠的蛋白质的毒性作用（错误翻译诱导的错误折叠[MIM]假说）。在这里，我提出了一个模型，解释了进化速率和表达水平的相关性选择功能。该模型的基础是选择使表达水平保持在最优水平附近，这反映了蛋白质功能的有益效果和表达的一些非特异性成本（例如，合成蛋白质的生物化学成本）。仿真结果证实了模型的预测。与MIM假设一样，该模型预测了经验观察到的其他几种关系。虽然该模型是基于蛋白质功能的选择，它是一致的发现，蛋白质的进化速度是最弱的相关性与其重要性的健身基因敲除实验测量。
There is great variation in the rates of sequence evolution among proteins encoded by the same genome. The strongest correlate of evolutionary rate is expression level: highly expressed proteins tend to evolve slowly. This observation has led to the proposal that a major determinant of protein evolutionary rate involves the toxic effects of protein that misfolds due to transcriptional and translational errors (the mistranslation-induced misfolding [MIM] hypothesis). Here, I present a model that explains the correlation of evolutionary rate and expression level by selection for function. The basis of this model is that selection keeps expression levels near optima that reflect a trade-off between beneficial effects of the protein's function and some nonspecific cost of expression (e.g., the biochemical cost of synthesizing protein). Simulations confirm the predictions of the model. Like the MIM hypothesis, this model predicts several other relationships that are observed empirically. Although the model is based on selection for protein function, it is consistent with findings that a protein's rate of evolution is at most weakly correlated with its importance for fitness as measured by gene knockout experiments.
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