School of Biotechnology, Gautam Buddha University, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, India.
Molecular Genetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Sci Rep. 2023 Jan 9;13(1):415. doi: 10.1038/s41598-022-27164-0.
Mycobacterium tuberculosis (Mtb) is a slow-growing, intracellular pathogen that exhibits a high GC-rich genome. Several factors, including the GC content of the genome, influence the evolution of specific codon usage biases in genomes. As a result, the Mtb genome exhibits strong biases for amino acid usage and codon usage. Codon usage of mRNAs affects several aspects of translation, including accuracy, efficiency, and protein folding. Here we address the effect of codon usage biases in determining the translation efficiency of mRNAs in Mtb. Unlike most commonly studied organisms, Mtb carries a single copy of each tRNA gene. However, we show that the relative levels of tRNAs in the Mtb tRNA pool vary by an order of magnitude. Our results show that the codons decoded by the abundant tRNAs indeed show higher adaptability. Moreover, there is a general positive correlation between genomic codon usage and the tRNA adaptability of codons (TAc). We further estimated the optimality of the codon and mRNAs by considering both the TAc and the tRNA demand. These measures did not show any correlation with mRNA abundance and translation efficiency. There was no correlation between tRNA adaptability and ribosome pausing as well. Taken together, we conclude that the translation machinery, and the tRNA pool of an organism, co-evolve with the codon usage to optimize the translation efficiency of an organism. Thus the deleterious effect of maladapted codons is not pronounced.
结核分枝杆菌（Mtb）是一种生长缓慢的细胞内病原体，具有高 GC 含量的基因组。包括基因组 GC 含量在内的几个因素，影响了基因组中特定密码子使用偏好的进化。因此，Mtb 基因组表现出强烈的氨基酸和密码子使用偏好。mRNA 的密码子使用会影响翻译的几个方面，包括准确性、效率和蛋白质折叠。在这里，我们研究了密码子使用偏倚对 Mtb 中 mRNA 翻译效率的影响。与大多数通常研究的生物体不同，Mtb 每个 tRNA 基因只有一个拷贝。然而，我们表明，MtbtRNA 池中的 tRNA 相对水平相差一个数量级。我们的结果表明，由丰富的 tRNA 解码的密码子确实表现出更高的适应性。此外，基因组密码子使用与密码子的 tRNA 适应性（TAc）之间存在普遍的正相关关系。我们进一步通过考虑 TAc 和 tRNA 需求来估计密码子和 mRNA 的最优性。这些措施与 mRNA 丰度和翻译效率没有相关性。tRNA 适应性与核糖体暂停之间也没有相关性。总之，我们得出结论，翻译机制和生物体的 tRNA 池与密码子使用一起进化，以优化生物体的翻译效率。因此，适应不良的密码子的有害影响并不明显。
