Brajesh R G, Raj Nikhil, Saini Supreet
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai - 400 076, India.
Mol Biosyst. 2017 Mar 28;13(4):796-803. doi: 10.1039/c6mb00765a.
How does a transcription network arrive at the particular values of biochemical interactions defining it? These interactions define DNA-transcription factor interaction, degradation rates of proteins, promoter strengths, and communication of the environmental signal with the network. What is the structure of the fitness landscape that is defined by the space that these parameters can take on? To answer these questions, we simulate the simplest regulatory network: a transcription factor, R, and a target protein, T. We use a cost-benefit analysis to evolve the network and eventually arrive at values of parameters which maximize fitness. We show that for a given topology, multiple parameter sets exist which confer maximal fitness to the cell, and that pairwise correlations exist between parameters in optimal sets. In addition, our results indicate that in the parameter space defining the interactions in a topology, a highly rugged fitness landscape exists.
转录网络是如何得出定义它的生化相互作用的特定值的?这些相互作用定义了DNA与转录因子的相互作用、蛋白质的降解速率、启动子强度以及环境信号与网络的通信。由这些参数所能取值的空间所定义的适应度景观的结构是怎样的?为了回答这些问题,我们模拟了最简单的调控网络:一个转录因子R和一个靶蛋白T。我们使用成本效益分析来进化该网络,并最终得出使适应度最大化的参数值。我们表明,对于给定的拓扑结构,存在多个能赋予细胞最大适应度的参数集,并且最优集中的参数之间存在成对相关性。此外,我们的结果表明,在定义拓扑结构中相互作用的参数空间里,存在一个高度崎岖的适应度景观。