Cross-evaluation of E. coli's operon structures via a whole-cell model suggests alternative cellular benefits for low- versus high-expressing operons.

Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-27 DOI:10.1016/j.cels.2024.02.002
Gwanggyu Sun, Mialy M DeFelice, Taryn E Gillies, Travis A Ahn-Horst, Cecelia J Andrews, Markus Krummenacker, Peter D Karp, Jerry H Morrison, Markus W Covert
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Abstract

Many bacteria use operons to coregulate genes, but it remains unclear how operons benefit bacteria. We integrated E. coli's 788 polycistronic operons and 1,231 transcription units into an existing whole-cell model and found inconsistencies between the proposed operon structures and the RNA-seq read counts that the model was parameterized from. We resolved these inconsistencies through iterative, model-guided corrections to both datasets, including the correction of RNA-seq counts of short genes that were misreported as zero by existing alignment algorithms. The resulting model suggested two main modes by which operons benefit bacteria. For 86% of low-expression operons, adding operons increased the co-expression probabilities of their constituent proteins, whereas for 92% of high-expression operons, adding operons resulted in more stable expression ratios between the proteins. These simulations underscored the need for further experimental work on how operons reduce noise and synchronize both the expression timing and the quantity of constituent genes. A record of this paper's transparent peer review process is included in the supplemental information.

通过全细胞模型对大肠杆菌操作子结构的交叉评估表明,低表达操作子和高表达操作子在细胞中具有不同的益处。
许多细菌利用操作子来核心化基因,但目前仍不清楚操作子如何使细菌受益。我们将大肠杆菌的 788 个多分录操作子和 1,231 个转录单元整合到现有的全细胞模型中,发现提出的操作子结构与模型参数化的 RNA-seq 读数之间存在不一致。我们通过对两个数据集进行迭代、模型指导修正,包括修正被现有比对算法误报为零的短基因的 RNA-seq 计数,解决了这些不一致问题。由此得出的模型显示了操作子使细菌获益的两种主要模式。在86%的低表达操作子中,添加操作子增加了其组成蛋白质的共表达概率;而在92%的高表达操作子中,添加操作子使蛋白质之间的表达比率更加稳定。这些模拟突显了进一步开展实验研究的必要性,即操作子如何减少噪音并使组成基因的表达时间和数量同步。补充信息中包含了本文透明的同行评审过程记录。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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