Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs
Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs
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DOI：
10.1038/ng1451
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发表时间：
2004-11-01
期刊：
影响因子：
30.8
通讯作者：
Kondrashov, FA
中科院分区：
文献类型：
--
作者：
Kern, AD;Kondrashov, FA
蛋白质和 RNA 分子的功能取决于位点之间复杂的上位相互作用。因此，可以通过补偿性第二位点取代(1,2) 来抑制突变的有害影响。在将线粒体基因编码的人类 tRNA 中的 86 个致病性突变与其哺乳动物直系同源物的序列联系起来时，我们注意到一种或几种非人类哺乳动物的正常 tRNA 中存在 52 个致病性突变。我们发现了至少五种补偿机制，用于破坏四个 tRNA 茎之一中的 Watson-Crick 对的 32 个致病性突变：恢复受影响的 Watson-Crick 相互作用（25 例）、加强另一对（4 例）、创建新对（8 例）、受影响茎中多重相互作用的变化（11 例）以及涉及环和茎结构之间相互作用的变化（3 例）。致病性突变及其补偿性取代在一个谱系中快速连续地固定，并且补偿性相互作用通常在不同的进化枝中趋同进化。进化中的哺乳动物 tRNA 中至少 10%，或许多达 50% 的核苷酸取代参与了这种相互作用，表明 tRNA 的进化沿着高度上位适应脊进行。
The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution(1,2). In relating a list of 86 pathogenic mutations in human tRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian tRNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges.