Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg, France.
Department of Computer Science, ICube, CNRS, University of Strasbourg, Strasbourg, France; Unité de Microbiologie Structurale, Institut Pasteur, CNRS, 75724, Paris Cedex 15, France; Université Paris Diderot, Sorbonne Paris Cité, 75724, Paris Cedex 15, France.
Biosystems. 2021 May;203:104368. doi: 10.1016/j.biosystems.2021.104368. Epub 2021 Feb 7.
The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X and called X motifs, allow identification and maintenance of the reading frame in genes. X motifs are significantly enriched in protein-coding genes, but have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements of protein-coding genes. First, we identify the codons of the X circular code which are frequent or rare in each domain of life (archaea, bacteria, eukaryota) and show that, for the amino acids with the highest codon bias, the preferred codon is often an X codon. We also observe a correlation between the 20 X codons and the optimal codons/dicodons that have been shown to influence translation efficiency. Then, we examined recently published experimental results concerning gene expression levels in diverse organisms. The approach used is the analysis of X motifs according to their density d(X), i.e. the number of X motifs per kilobase in a gene sequence s. Surprisingly, this simple parameter identifies several unexpected relations between the X circular code and gene expression. For example, the X motifs are significantly enriched in the minimal gene set belonging to the three domains of life, and in codon-optimized genes. Furthermore, the density of X motifs generally correlates with experimental measures of translation efficiency and mRNA stability. Taken together, these results lead us to propose that the X motifs may represent a genetic signal contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.
X 环码是一组 20 个三核苷酸（密码子），已在大多数生物体（细菌、古菌、真核生物、质粒、病毒）的蛋白质编码基因中被发现。此前已经表明，X 环码具有作为纠错码的重要数学性质。因此，X 环码的模体，即属于 X 的一系列密码子，称为 X 模体，允许在基因中识别和维持阅读框。X 模体在蛋白质编码基因中显著富集，但也在许多转移 RNA(tRNA)基因和核糖体 RNA(rRNA)的重要功能区域中被识别，特别是在肽酰转移酶中心和解码中心。在这里，我们研究了 X 模体作为蛋白质编码基因功能元件的潜在作用。首先，我们确定了在生命的每个领域（古菌、细菌、真核生物）中频繁或罕见的 X 环码密码子，并表明对于具有最高密码子偏好性的氨基酸，首选密码子通常是 X 密码子。我们还观察到 20 个 X 密码子与已证明影响翻译效率的最佳密码子/双密码子之间存在相关性。然后，我们检查了最近发表的关于不同生物体中基因表达水平的实验结果。所使用的方法是根据其密度 d(X)分析 X 模体，即基因序列 s 中每千碱基的 X 模体数量。令人惊讶的是，这个简单的参数确定了 X 环码与基因表达之间的几个意外关系。例如，X 模体在属于生命的三个领域的最小基因集中以及在密码子优化基因中显著富集。此外，X 模体的密度通常与翻译效率和 mRNA 稳定性的实验测量相关。总之，这些结果使我们提出 X 模体可能代表遗传信号，有助于维持正确的阅读框以及基因表达的优化和调节。
