Milner Centre for Evolution, University of Bath, Bath, United Kingdom.
Mol Biol Evol. 2022 Jan 7;39(1). doi: 10.1093/molbev/msab326.
In bacteria stop codons are recognized by one of two class I release factors (RF1) recognizing TAG, RF2 recognizing TGA, and TAA being recognized by both. Variation across bacteria in the relative abundance of RF1 and RF2 is thus hypothesized to select for different TGA/TAG usage. This has been supported by correlations between TAG:TGA ratios and RF1:RF2 ratios across multiple bacterial species, potentially also explaining why TAG usage is approximately constant despite extensive variation in GC content. It is, however, possible that stop codon trends are determined by other forces and that RF ratios adapt to stop codon usage, rather than vice versa. Here, we determine which direction of the causal arrow is the more parsimonious. Our results support the notion that RF1/RF2 ratios become adapted to stop codon usage as the same trends, notably the anomalous TAG behavior, are seen in contexts where RF1:RF2 ratios cannot be, or are unlikely to be, causative, that is, at 3'untranslated sites never used for translation termination, in intragenomic analyses, and across archaeal species (that possess only one RF1). We conclude that specifics of RF biology are unlikely to fully explain TGA/TAG relative usage. We discuss why the causal relationships for the evolution of synonymous stop codon usage might be different from those affecting synonymous sense codon usage, noting that transitions between TGA and TAG require two-point mutations one of which is likely to be deleterious.
在细菌中，终止密码子被两种类型的 I 类释放因子（RF1）识别，其中 RF1 识别 TAG，RF2 识别 TGA，而 TAA 则被两者识别。因此，细菌中 RF1 和 RF2 的相对丰度的变化被假设为选择了不同的 TGA/TAG 使用方式。这一假设得到了多个细菌物种中 TAG:TGA 比值与 RF1:RF2 比值之间相关性的支持，这也可能解释了为什么尽管 GC 含量存在广泛变化，但 TAG 的使用仍然相对稳定。然而，终止密码子的趋势可能是由其他力量决定的，而 RF 比值适应终止密码子的使用，而不是相反。在这里，我们确定因果关系的箭头方向更具简约性。我们的研究结果支持这样一种观点，即 RF1/RF2 比值会适应终止密码子的使用，因为相同的趋势，特别是异常的 TAG 行为，在 RF1:RF2 比值不能或不太可能成为原因的情况下也可以看到，即在从未用于翻译终止的 3'非翻译区，在基因组内分析中和在古菌物种中（它们只拥有一种 RF1）。我们得出的结论是，RF 生物学的具体细节不太可能完全解释 TGA/TAG 的相对使用情况。我们讨论了为什么同义终止密码子使用的进化的因果关系可能与影响同义同义密码子使用的因果关系不同，并指出 TGA 和 TAG 之间的转换需要两个点突变，其中一个很可能是有害的。
