Synonymous codon ordering: a subtle but prevalent strategy of bacteria to improve translational efficiency.

In yeast coding sequences, once a particular codon has been used, subsequent occurrence of the same amino acid tends to use codons sharing the same tRNA. Such a phenomenon of co-tRNA codons pairing bias (CTCPB) is also found in some other eukaryotes but it is not known whether it occurs in prokaryotes. In this study, we focused on a total of 773 bacterial genomes to investigate their synonymous codon pairing preferences. After calculating the actual frequencies of synonymous codon pairs and comparing them with their expected values, we detected an obvious pairing bias towards identical codon pairs. This seems consistent with the previously reported CTCPB phenomenon, since identical codons are certainly read by the same tRNA. However, among co-tRNA but non-identical codon pairs, only 22 were often found overrepresented, suggesting that many co-tRNA codons actually do not preferentially pair together in prokaryotes. Therefore, the previously reported co-tRNA codons pairing rule needs to be more rigorously defined. The affinity differences between a tRNA anticodon and its readable codons should be taken into account. Moreover, both within-gene-shuffling tests and phylogenetic analyses support the idea that translational selection played an important role in shaping the observed synonymous codon pairing pattern in prokaryotes. Overall, a high level of synonymous codon pairing bias was detected in 73% investigated bacterial species, suggesting the synonymous codon ordering strategy has been prevalently adopted by prokaryotes to improve their translational efficiencies. The findings in this study also provide important clues to better understand the complex dynamics of translational process.

在酵母编码序列中，一旦使用了某个特定的密码子，后续出现的相同氨基酸往往会使用共用同一转运RNA（tRNA）的密码子。这种共tRNA密码子配对偏好（CTCPB）现象在其他一些真核生物中也有发现，但在原核生物中是否存在尚不清楚。 在本研究中，我们聚焦于总共773个细菌基因组以研究它们的同义密码子配对偏好。在计算了同义密码子对的实际频率并将其与预期值进行比较之后，我们检测到对相同密码子对存在明显的配对偏好。这似乎与先前报道的CTCPB现象相符，因为相同的密码子肯定是由同一tRNA读取的。然而，在共tRNA但不相同的密码子对中，只有22种经常被发现出现频率过高，这表明在原核生物中许多共tRNA密码子实际上并不会优先配对在一起。因此，先前报道的共tRNA密码子配对规则需要更严格地定义。应考虑tRNA反密码子与其可识别密码子之间的亲和力差异。此外，基因内重排检验和系统发育分析都支持这样的观点，即翻译选择在塑造原核生物中观察到的同义密码子配对模式方面发挥了重要作用。 总体而言，在73%的被研究细菌物种中检测到了高度的同义密码子配对偏好，这表明同义密码子排序策略已被原核生物普遍采用以提高其翻译效率。本研究的发现也为更好地理解翻译过程的复杂动态提供了重要线索。