Why highly expressed proteins evolve slowly
Why highly expressed proteins evolve slowly
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DOI：
10.1073/pnas.0504070102
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发表时间：
2005-10-04
影响因子：
11.1
通讯作者：
Arnold, FH
中科院分区：
文献类型：
--
作者：
Drummond, DA;Bloom, JD;Arnold, FH
最近的许多工作已经探索了蛋白质序列进化速率的分子和群体遗传约束。进化速率的最佳预测因子是表达水平，其原因尚不清楚。在这里，我们假设，选择，以减少蛋白质错误折叠的负担将有利于蛋白质序列的翻译错义错误的鲁棒性增加。翻译稳健性的压力随着表达水平的增加而增加，并约束序列进化。使用几个测序的酵母基因组，全球表达和蛋白质丰度的数据，和一套旁系同源物可追溯到一个古老的全基因组复制酵母，我们排除了几个混淆的影响，并表明表达水平解释了大约一半的酿酒酵母蛋白质进化速率的变化。我们研究表达的主导作用的原因，发现全基因组测试有利于翻译的鲁棒性解释现有的假设，调用功能或翻译效率的限制。我们的研究结果表明，蛋白质的进化速度与其功能基本无关，这可以解释为什么高表达的蛋白质在生命树中进化缓慢。
Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons that have remained unexplained. Here, we hypothesize that-selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions and can explain why highly expressed proteins evolve slowly across the tree of life.