New Jersey City University, Jersey City, New Jersey, USA.
Department of Genetics, Rutgers University, Piscataway, New Jersey, USA.
Genome Biol Evol. 2024 May 2;16(5). doi: 10.1093/gbe/evae080.
Rosenberg AA, Marx A, Bronstein AM (Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon. Nat Commun. 2022:13:2815) 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 (i) have random codon usage, (ii) codon usage determined by mutation biases, and (iii) 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 were 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.
罗森伯格等人（Rosenberg AA, Marx A, Bronstein AM）最近发现同义密码子使用与产生的氨基酸的二面角键之间存在惊人的相关性。然而，他们的分析没有考虑到已知最强的密码子使用相关因素：基因表达。我们通过应用罗森伯格等人的方法，重新检查了键角与密码子使用之间的关系，该方法适用于具有（i）随机密码子使用、（ii）由突变偏倚决定的密码子使用和（iii）通过选择-突变-漂移平衡假设保持密码子使用与基因表达之间一般关系的模拟蛋白质编码序列。当密码子使用完全随机时，我们观察到二面角键和密码子使用之间的相关性，表明同义密码子之间的键角分布差异可能与噪声混淆。与密码子使用模式的一般分析更相关的是，我们发现真实序列分析与假设选择-突变-漂移平衡的序列模拟分析之间存在惊人的一致性，在前者中检测到的 91%显著同义密码子对在后者中也被检测到。我们认为，密码子使用与二面角键之间的相关性是由于基因突变偏向、翻译效率的自然选择和基因表达之间的相互作用导致基因间密码子使用的变化所致，进一步强调在寻找与密码子使用相关的新模式时，必须控制这些因素。
