摘要

细胞生长由底物可用性和细胞的代谢能力决定，以将底物同化成构件。决定生长速率的代谢基因可以协同或拮抗地相互作用，并且可以根据遗传背景和环境条件加速或减缓生长。我们发展了一系列不同的大肠埃希氏菌单基因缺失突变体，其生长速度范围和确定的突变通常会提高生长速度。尽管亲本菌株之间存在代谢差异，增强生长的突变主要定位于核心转录机器，包括RNA聚合酶（RNAP）的β和β'亚基以及转录延伸因子NusA。确定增强生长的RNAP的结构区段先前已经涉及抗生素抗性以及转录延伸和暂停的控制。我们进一步开发了一个计算框架来描述获得这些突变后发生的转录变化如何影响菌株之间的生长速率。我们的实验和计算结果为RNAP突变改变活性转录和基因沉默之间竞争平衡的情况提供了证据。这项研究表明RNAP特定区域的突变是一种可以增强不同代谢状态细胞生长速度的趋同适应性解决方案。

Cell growth is determined by substrate availability and the cell's metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow growth, depending on genetic background and environmental conditions. We evolved a diverse set of Escherichia coli single-gene deletion mutants with a spectrum of growth rates and identified mutations that generally increase growth rate. Despite the metabolic differences between parent strains, mutations that enhanced growth largely mapped to core transcription machinery, including the β and β' subunits of RNA polymerase (RNAP) and the transcription elongation factor, NusA. The structural segments of RNAP that determine enhanced growth have been previously implicated in antibiotic resistance and in the control of transcription elongation and pausing. We further developed a computational framework to characterize how the transcriptional changes that occur upon acquisition of these mutations affect growth rate across strains. Our experimental and computational results provide evidence for cases in which RNAP mutations shift the competitive balance between active transcription and gene silencing. This study demonstrates that mutations in specific regions of RNAP are a convergent adaptive solution that can enhance the growth rate of cells from distinct metabolic states.

https://www.ncbi.nlm.nih.gov/pubmed/29584733