Sequence Coevolution between RNA and Protein Characterized by Mutual Information between Residue Triplets
Sequence Coevolution between RNA and Protein Characterized by Mutual Information between Residue Triplets
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DOI：
10.1371/journal.pone.0030022
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发表时间：
2012-01-18
期刊：
影响因子：
3.7
通讯作者：
Pande, Vijay S.
中科院分区：
文献类型：
--
作者：
Brandman, Relly;Brandman, Yigal;Pande, Vijay S.
多序列比对中的共进化残基提供了三维结构中生物物理相互作用的进化线索。尽管有丰富的文献描述了蛋白质内或蛋白质之间的氨基酸协同进化和RNA内的核酸协同进化，但迄今为止还没有蛋白质和RNA之间协同进化的直接证据。核糖体是一种结构保守的大分子机器，由50多个相互作用的蛋白质和RNA链组成，它提供了一个可能共同进化的RNA/蛋白质相互作用的自然例子。我们提供了第一个直接的证据，RNA/蛋白质的共同进化的特征的相互信息，从核糖体蛋白L22和相邻的23 S RNA的多序列比对的残基三联体。我们将残基三联体定义为多重序列比对中的三个位置，其中一个位置来自23 S RNA，两个位置来自L22蛋白。我们发现，具有高互信息的残基三联体比残基三联体更有可能在3D空间中接近。一些高互信息残基三联体在L22蛋白质结构中聚集成一个相连的系列，类似于蛋白质协同进化中观察到的模式。我们还描述了RNA核苷酸，其中从一个核苷酸切换到另一个（或嘌呤和嘧啶之间）导致近端氨基酸位置的氨基酸分布变化。进化上不同的核糖体种类的多晶体结构可以为这些差异提供结构证据。对于一个残基三联体，一个物种中的嘧啶是另一个物种中的嘌呤，并且RNA/蛋白质氢键存在于一个物种中，而不是另一个物种。结果提供了第一个直接的证据，RNA/蛋白质协同进化，通过使用高阶互信息，这表明，生物物理相互作用的RNA和蛋白质链的约束确实是一个驱动力，在他们的进化。
Coevolving residues in a multiple sequence alignment provide evolutionary clues of biophysical interactions in 3D structure. Despite a rich literature describing amino acid coevolution within or between proteins and nucleic acid coevolution within RNA, to date there has been no direct evidence of coevolution between protein and RNA. The ribosome, a structurally conserved macromolecular machine composed of over 50 interacting protein and RNA chains, provides a natural example of RNA/protein interactions that likely coevolved. We provide the first direct evidence of RNA/protein coevolution by characterizing the mutual information in residue triplets from a multiple sequence alignment of ribosomal protein L22 and neighboring 23S RNA. We define residue triplets as three positions in the multiple sequence alignment, where one position is from the 23S RNA and two positions are from the L22 protein. We show that residue triplets with high mutual information are more likely than residue doublets to be proximal in 3D space. Some high mutual information residue triplets cluster in a connected series across the L22 protein structure, similar to patterns seen in protein coevolution. We also describe RNA nucleotides for which switching from one nucleotide to another (or between purines and pyrimidines) results in a change in amino acid distribution for proximal amino acid positions. Multiple crystal structures for evolutionarily distinct ribosome species can provide structural evidence for these differences. For one residue triplet, a pyrimidine in one species is a purine in another, and RNA/protein hydrogen bonds are present in one species but not the other. The results provide the first direct evidence of RNA/protein coevolution by using higher order mutual information, suggesting that biophysical constraints on interacting RNA and protein chains are indeed a driving force in their evolution.