Coton Charlotte, Talbot Grégoire, Le Louarn Maud, Dillmann Christine, de Vienne Dominique
Université Paris-Saclay, INRAE, CNRS, AgroParisTech, GQE - Le Moulon, 91190 Gif-sur-Yvette, France.
Université Paris-Saclay, INRAE, CNRS, AgroParisTech, GQE - Le Moulon, 91190 Gif-sur-Yvette, France.
J Theor Biol. 2022 Apr 7;538:111015. doi: 10.1016/j.jtbi.2022.111015. Epub 2022 Jan 10.
The central role of metabolism in cell functioning and adaptation has given rise to countless studies on the evolution of enzyme-coding genes and network topology. However, very few studies have addressed the question of how enzyme concentrations change in response to positive selective pressure on the flux, considered a proxy of fitness. In particular, the way cellular constraints, such as resource limitations and co-regulation, affect the adaptive landscape of a pathway under selection has never been analyzed theoretically. To fill this gap, we developed a model of the evolution of enzyme concentrations that combines metabolic control theory and an adaptive dynamics approach, and integrates possible dependencies between enzyme concentrations. We determined the evolutionary equilibria of enzyme concentrations and their range of neutral variation, and showed that they differ with the properties of the enzymes, the constraints applied to the system and the initial enzyme concentrations. Simulations of long-term evolution confirmed all analytical and numerical predictions, even though we relaxed the simplifying assumptions used in the analytical treatment.
新陈代谢在细胞功能和适应性方面的核心作用引发了无数关于酶编码基因进化和网络拓扑结构的研究。然而，很少有研究探讨酶浓度如何响应通量上的正选择压力而变化，通量被视为适应性的一个指标。特别是，细胞限制因素，如资源限制和共同调节，如何影响处于选择中的一条途径的适应度景观，从未在理论上进行过分析。为了填补这一空白，我们开发了一个酶浓度进化模型，该模型结合了代谢控制理论和自适应动力学方法，并整合了酶浓度之间可能的依赖性。我们确定了酶浓度的进化平衡点及其中性变异范围，并表明它们因酶的特性、应用于系统的限制以及初始酶浓度而异。长期进化模拟证实了所有的分析和数值预测，尽管我们放宽了分析处理中使用的简化假设。
