Rosenberg et al. (2022) recently found a surprising correlation between synonymous codon usage and the dihedral bond angles of the resulting amino acid. However, their analysis did not account for the strongest known correlate of codon usage: gene expression. We re-examined the relationship between bond angles and codon usage by applying the approach of Rosenberg et al. to simulated protein-coding sequences that (1) have random codon usage, (2) codon usage determined by mutation biases, and (3) maintain the general relationship between codon usage and gene expression via the assumption of selection-mutation-drift equilibrium. We observed correlations between dihedral bond angle and codon usage when codon usage is entirely random, indicating possible conflation of noise with differences in bond angle distributions between synonymous codons. More relevant to the general analysis of codon usage patterns, we found surprisingly good agreement between the analysis of the real sequences and the analysis of sequences simulated assuming selection-mutation-drift equilibrium, with 91% of significant synonymous codon pairs detected in the former also detected in the latter. We believe the correlation between codon usage and dihedral bond angles resulted from the variation in codon usage across genes due to the interplay between mutation bias, natural selection for translation efficiency, and gene expression, further underscoring these factors must be controlled for when looking for novel patterns related to codon usage.

中文翻译：

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重新检查大肠杆菌中同义密码子使用和蛋白质键角之间的相关性

罗森伯格等人。 （2022）最近发现同义密码子的使用和所得氨基酸的二面键角之间存在令人惊讶的相关性。然而，他们的分析并没有考虑到密码子使用的最强已知相关性：基因表达。我们通过应用 Rosenberg 等人的方法重新检查了键角和密码子使用之间的关系。模拟蛋白质编码序列（1）具有随机密码子使用，（2）由突变偏差决定的密码子使用，以及（3）通过选择-突变-漂移平衡的假设维持密码子使用和基因表达之间的一般关系。当密码子使用完全随机时，我们观察到二面键角和密码子使用之间的相关性，表明噪声可能与同义密码子之间键角分布的差异相混淆。与密码子使用模式的一般分析更相关，我们发现真实序列的分析和假设选择-突变-漂移平衡的模拟序列分析之间惊人地一致，其中 91% 的重要同义密码子对也在前者中检测到检测到后者。我们认为密码子使用和二面键角之间的相关性是由于突变偏差、翻译效率的自然选择和基因表达之间的相互作用而导致跨基因密码子使用的变化，进一步强调在寻找新的基因时必须控制这些因素与密码子使用相关的模式。