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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Specificity in protein interactions and its relationship with sequence diversity and coevolution
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Specificity in protein interactions and its relationship with sequence diversity and coevolution

机译:蛋白质相互作用的特异性及其与序列多样性和协同进化的关系

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Studies of interacting proteins have found correlated evolution of the sequences of binding partners, apparently as a result of compensating mutations to maintain specificity (i.e., molecular coevolution). Here, we analyze the coevolution of interacting proteins in yeast and demonstrate correlated evolution of binding partners in eukaryotes. Detailed investigation of this apparent coevolution, focusing on the proteins' surface and binding interface, surprisingly leads to no improvement in the correlation. We conclude that true coevolution, as characterized by compensatory mutations between binding partners, is unlikely to be chiefly responsible for the apparent correlated evolution. We postulate that the correlation between sequence alignments is simply due to interacting proteins being subject to similar constraints on their evolutionary rate. Because gene expression has a strong influence on evolutionary rate, and interacting proteins will tend to have similar levels of expression, we investigated this particular constraint. We found that the absolute expression level outperformed correlated evolution for predicting interacting protein partners. A correlation between sequence alignments could also be identified not only between pairs of proteins that physically interact but also between those that are merely functionally related (i.e., within the same protein complex). This indicates that the observed correlated evolution of interacting proteins is due to similar constraints on evolutionary rate and not coevolution.
机译:相互作用蛋白的研究发现结合伴侣序列的相关进化,显然是由于补偿突变以维持特异性(即分子协同进化)的结果。在这里,我们分析了酵母中相互作用蛋白的共同进化,并证明了真核生物中结合伴侣的相关进化。对这种明显的共进化的详细研究,集中在蛋白质的表面和结合界面上,令人惊讶地导致相关性没有改善。我们得出的结论是,以结合伴侣之间的补偿性突变为特征的真正的协同进化不太可能主要负责表观相关进化。我们推测序列比对之间的相关性仅仅是由于相互作用的蛋白质在其进化速率上受到类似的限制。因为基因表达对进化速率有很大影响,并且相互作用的蛋白质倾向于具有相似的表达水平,所以我们研究了这种特殊的限制。我们发现,绝对表达水平优于相关的进化,以预测相互作用的蛋白质伴侣。序列比对之间的相关性不仅可以在物理相互作用的蛋白质对之间识别,而且还可以在仅在功能上相关的蛋白质对之间识别(即,在同一蛋白质复合物中)。这表明观察到的相互作用蛋白的相关进化是由于对进化速率的相似限制而不是协同进化。

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