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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >ROBUSTNESS, STABILITY AND EFFICIENCY OF PHAGE λ GENETIC SWITCH: DYNAMICAL STRUCTURE ANALYSIS
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ROBUSTNESS, STABILITY AND EFFICIENCY OF PHAGE λ GENETIC SWITCH: DYNAMICAL STRUCTURE ANALYSIS

机译：噬菌体λ遗传开关的鲁棒性，稳定性和效率：动态结构分析

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Based on the dynamical structure theory for complex networks recently developed by one of us and on the physical-chemical models for gene regulation, developed by Shea and Ackers in the 1980's, we formulate a direct and concise mathematical framework for the genetic switch controlling phage λ life cycles, which naturally includes the stochastic effect. The dynamical structure theory states that the dynamics of a complex network is determined by its four elementary components: The dissipation (analogous to degradation), the stochastic force, the driving force determined by a potential, and the transverse force. The potential may be interpreted as a landscape for the phage development in terms of attractive basins, saddle points, peaks and valleys. The dissipation gives rise to the adaptivity of the phage in the landscape defined by the potential: The phage always has the tendency to approach the bottom of the nearby attractive basin. The transverse force tends to keep the network on the equal-potential contour of the landscape. The stochastic fluctuation gives the phage the ability to search around the potential landscape by passing through saddle points. With molecular parameters in our model fixed primarily by the experimental data on wild-type phage and supplemented by data on one mutant, our calculated results on mutants agree quantitatively with the available experimental observations on other mutants for protein number, lysogenization frequency, and a lysis frequency in lysogen culture. The calculation reproduces the observed robustness of the phage λ genetic switch. This is the first mathematical description that successfully represents such a wide variety of major experimental phenomena. Specifically, we find: (1) The explanation for both the stability and the efficiency of phage λ genetic switch is the exponential dependence of saddle point crossing rate on potential barrier height, a result of the stochastic motion in a landscape; and (2) The positive feedback of cI repressor gene transcription, enhanced by the CI dimer cooperative binding, is the key to the robustness of the phage λ genetic switch against mutations and fluctuations in kinetic parameter values.
机译：基于对我们之一的近最近开发的复杂网络的动态结构理论以及1980年代的Shea和Ackers开发的基因调节的物理化学模型，我们为控制噬菌体λ的遗传开关为直接和简明的数学框架生命周期，自然包括随机效果。动态结构理论指出复杂网络的动态由其四个基本组件确定：耗散（类似于劣化），随机力，由电位确定的驱动力和横向力。在有吸引力的盆地，马鞍点，山峰和山谷方面，潜力可能被解释为噬菌体发展的景观。耗散导致潜水所定义的景观中噬菌体的适应性：噬菌体总是具有接近附近有吸引力盆地的底部的趋势。横向力倾向于将网络保持在景观的平等电位轮廓上。随机波动使噬菌体通过通过鞍点来搜索潜在景观的能力。在我们的模型中的分子参数主要由野生型噬菌体的实验数据固定，并通过在一个突变体上补充数据，我们对突变体的计算结果定量地与蛋白质数，溶血化频率和裂解的其他突变体的可用实验观察结果溶血生培养的频率。该计算再现噬菌体λ遗传开关的观察到的鲁棒性。这是第一个成功代表各种主要实验现象的第一个数学描述。具体而言，我们发现：（1）稳定性和噬菌体遗传开关的稳定性和效率的说明是鞍点交叉率对势垒高度的指数依赖性，其随机运动在景观中的随机运动的结果; （2）CI压抑基因转录的阳性反馈，通过CI二聚体合作结合增强，是噬菌体λ遗传开关对突变和动力学参数值波动的稳健性的关键。

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