Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.
Mol Biol Evol. 2023 Sep 1;40(9). doi: 10.1093/molbev/msad189.
The most highly expressed genes in microbial genomes tend to use a limited set of synonymous codons, often referred to as "preferred codons." The existence of preferred codons is commonly attributed to selection pressures on various aspects of protein translation including accuracy and/or speed. However, gene expression is condition-dependent and even within single-celled organisms transcript and protein abundances can vary depending on a variety of environmental and other factors. Here, we show that growth rate-dependent expression variation is an important constraint that significantly influences the evolution of gene sequences. Using large-scale transcriptomic and proteomic data sets in Escherichia coli and Saccharomyces cerevisiae, we confirm that codon usage biases are strongly associated with gene expression but highlight that this relationship is most pronounced when gene expression measurements are taken during rapid growth conditions. Specifically, genes whose relative expression increases during periods of rapid growth have stronger codon usage biases than comparably expressed genes whose expression decreases during rapid growth conditions. These findings highlight that gene expression measured in any particular condition tells only part of the story regarding the forces shaping the evolution of microbial gene sequences. More generally, our results imply that microbial physiology during rapid growth is critical for explaining long-term translational constraints.
在微生物基因组中，表达水平最高的基因往往使用有限的同义密码子，通常被称为“偏好密码子”。偏好密码子的存在通常归因于对蛋白质翻译的各个方面的选择压力，包括准确性和/或速度。然而，基因表达是条件依赖性的，即使在单细胞生物中，转录物和蛋白质的丰度也会因各种环境和其他因素而变化。在这里，我们表明，生长速率依赖性表达变化是一个重要的限制因素，它显著影响基因序列的进化。我们使用大肠杆菌和酿酒酵母的大规模转录组和蛋白质组数据集，证实密码子使用偏好与基因表达强烈相关，但强调当在快速生长条件下进行基因表达测量时，这种关系最为明显。具体来说，在快速生长期间相对表达增加的基因具有比在快速生长条件下表达减少的可比表达基因更强的密码子使用偏好。这些发现强调了在任何特定条件下测量的基因表达仅能说明塑造微生物基因序列进化的部分原因。更一般地说，我们的结果表明，快速生长期间的微生物生理学对于解释长期翻译限制至关重要。
