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Protein misinteraction avoidance causes highly expressed proteins to evolve slowly.


ABSTRACT: The tempo and mode of protein evolution have been central questions in biology. Genomic data have shown a strong influence of the expression level of a protein on its rate of sequence evolution (E-R anticorrelation), which is currently explained by the protein misfolding avoidance hypothesis. Here, we show that this hypothesis does not fully explain the E-R anticorrelation, especially for protein surface residues. We propose that natural selection against protein-protein misinteraction, which wastes functional molecules and is potentially toxic, constrains the evolution of surface residues. Because highly expressed proteins are under stronger pressures to avoid misinteraction, surface residues are expected to show an E-R anticorrelation. Our molecular-level evolutionary simulation and yeast genomic analysis confirm multiple predictions of the hypothesis. These findings show a pluralistic origin of the E-R anticorrelation and reveal the role of protein misinteraction, an inherent property of complex cellular systems, in constraining protein evolution.

SUBMITTER: Yang JR 

PROVIDER: S-EPMC3325723 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Protein misinteraction avoidance causes highly expressed proteins to evolve slowly.

Yang Jian-Rong JR   Liao Ben-Yang BY   Zhuang Shi-Mei SM   Zhang Jianzhi J  

Proceedings of the National Academy of Sciences of the United States of America 20120313 14


The tempo and mode of protein evolution have been central questions in biology. Genomic data have shown a strong influence of the expression level of a protein on its rate of sequence evolution (E-R anticorrelation), which is currently explained by the protein misfolding avoidance hypothesis. Here, we show that this hypothesis does not fully explain the E-R anticorrelation, especially for protein surface residues. We propose that natural selection against protein-protein misinteraction, which wa  ...[more]

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