Fitness landscapes are a central concept in evolutionary biology and have been thoroughly detailed in terms of genotypes. However, our understanding of the selected metabolic and gene expression adaptations, and their dependence on genetic background, remains limited. Here, we reveal multi-scale adaptation principles in the E. coli species by taking multi-omics measurements of six different strains throughout their adaptive evolution to glucose minimal media. Statistics and matrix factorization is applied to yield four key results. First, analysis of the metabolic and physiological data shows evolutionary convergence in growth rate, glucose uptake rate, glycolytic ATP and NADH production but divergence in NADPH production strategies. Second, factorization-based analysis of the transcriptome revealed six conserved transcriptomic adaptations describing increased expression of ribosome and amino acid biosynthetic genes and decreased expression of stress response and structural genes. Third, correlation analysis identifies five tradeoffs underlying the transcriptomic profiles. Fourth, statistical tests leveraging ALE design identify four mutation-flux correlates and eight mutation-transcriptomic correlates that link mutations to systems level adaptation principles. Our total results reveal the dominant metabolic and regulatory constraints governing E. coli growth adaptation that either distinguish strains or are conserved principles.

中文翻译：

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多种大肠杆菌菌株的实验室进化揭示了适应的统一原理，但驱动基因型具有多样性

适应性景观是进化生物学中的核心概念，并且已在基因型方面进行了详细介绍。但是，我们对所选的代谢和基因表达适应及其对遗传背景的依赖性的了解仍然有限。在这里，我们通过对六个不同菌株在其对葡萄糖基本培养基的适应性进化过程中的六种不同菌株进行多组学测量，揭示了大肠杆菌中的多尺度适应性原理。应用统计和矩阵分解产生四个关键结果。首先，对代谢和生理数据的分析显示出生长速率，葡萄糖摄取速率，糖酵解ATP和NADH产生的进化趋同，但NADPH产生策略存在分歧。第二，基于转录因子分析的转录组分析发现六种保守的转录组适应性变化，描述了核糖体和氨基酸生物合成基因的表达增加以及应激反应和结构基因的表达减少。第三，相关分析确定了转录组概况的五个权衡。第四，利用ALE设计进行的统计测试确定了将突变与系统级适应性原理联系起来的四个突变通量相关性和八个突变-转录组相关性。我们的总结果揭示了支配大肠杆菌生长适应性的主要代谢和调节限制因素，这些限制因素可以区分菌株还是保守原理。相关分析确定了转录组概况的五个权衡。第四，利用ALE设计进行的统计测试确定了将突变与系统级适应性原理联系起来的四个突变通量相关性和八个突变-转录组相关性。我们的总结果揭示了支配大肠杆菌生长适应性的主要代谢和调节限制因素，这些限制因素可以区分菌株还是保守原理。相关分析确定了转录组概况的五个权衡。第四，利用ALE设计进行的统计测试确定了将突变与系统级适应性原理联系起来的四个突变通量相关性和八个突变-转录组相关性。我们的总结果揭示了支配大肠杆菌生长适应性的主要代谢和调节限制因素，这些限制因素可以区分菌株还是保守原理。