Institute of Enzymology, Research Centre for Natural Sciences, Budapest, 1117, Hungary.
Sci Rep. 2023 Aug 31;13(1):14294. doi: 10.1038/s41598-023-41410-z.
In most eukaryotes and prokaryotes TGA is used at a significantly higher frequency than TAG as termination codon of protein-coding genes. Although this phenomenon has been recognized several years ago, there is no generally accepted explanation for the TAG-TGA paradox. Our analyses of human mutation data revealed that out of the eighteen sense codons that can give rise to a nonsense codon by single base substitution, the CGA codon is exceptional: it gives rise to the TGA stop codon at an order of magnitude higher rate than the other codons. Here we propose that the TAG-TGA paradox is due to methylation and hypermutabilty of CpG dinucleotides. In harmony with this explanation, we show that the coding genomes of organisms with strong CpG methylation have a significant bias for TGA whereas those from organisms that lack CpG methylation use TGA and TAG termination codons with similar probability.
在大多数真核生物和原核生物中，TGA 的使用频率明显高于 TAG，作为蛋白质编码基因的终止密码子。尽管这一现象早在几年前就已被认识到，但对于 TAG-TGA 悖论还没有一个普遍接受的解释。我们对人类突变数据的分析表明，在可能导致无意义密码子的 18 个同义密码子中，CGA 密码子是异常的：它导致 TGA 终止密码子的出现率比其他密码子高出一个数量级。在这里，我们提出 TAG-TGA 悖论是由于 CpG 二核苷酸的甲基化和超突变性。与这个解释一致的是，我们表明，具有强 CpG 甲基化的生物体的编码基因组对 TGA 有明显的偏向，而那些缺乏 CpG 甲基化的生物体则以相似的概率使用 TGA 和 TAG 终止密码子。
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