论文标题

基因表达动力学的紧密相关性作为资源竞争的足迹

Emergent Correlations in Gene Expression Dynamics as Footprints of Resource Competition

论文作者

Chakraborty, Priya, Ghosh, Sayantari

论文摘要

遗传回路需要一个细胞环境才能进行,该环境自然地将电路函数与基因调节网络的整体功能耦合。为了执行其功能,所有基因电路都以RNA聚合酶,核糖体和TRNA的形式绘制资源。最近的实验指出,资源竞争对合成电路输出的作用可能是巨大的。但是,尚未探索电路体系结构对资源共享动态的复杂性的影响。在本文中,我们采用数学建模和内部实验实验来确定资源权衡的来源并量化其对遗传回路功能的影响,从而使我们对立即下游蛋白的调节进行调节。我们以荧光记者的示例为例,这些记者通常用作蛋白质读出。我们表明,当资源受到限制并且核糖体亲和力不对称时,从下游蛋白数据读取中估计基因表达动力学可能是不可靠的。我们专注于mRNA拷贝数和RBS强度对以两个方案形式出现的非线性等线的影响,并以临界点为突出,并研究相关性和竞争如何根据各种电路参数互相占主导地位。为了进一步关注遗传切换电路,我们已经确定了该模型基序中资源竞争的主要影响,并量化了观测值。在湿实验实验中可以测试观察结果,因为所选的所有参数在实验中都是相关的。

Genetic circuits need a cellular environment to operate in, which naturally couples the circuit function with the overall functionality of gene regulatory network. To execute their functions all gene circuits draw resources in the form of RNA polymerases, ribosomes, and tRNAs. Recent experiments pointed out that the role of resource competition on synthetic circuit outputs could be immense. However, the effect of complexity of the circuit architecture on resource sharing dynamics is yet unexplored. In this paper, we employ mathematical modelling and in-silico experiments to identify the sources of resource trade-off and to quantify its impact on the function of a genetic circuit, keeping our focus on regulation of immediate downstream proteins. We take the example of the fluorescent reporters, which are often used as protein read-outs. We show that estimating gene expression dynamics from readings of downstream protein data might be unreliable when the resource is limited and ribosome affinities are asymmetric. We focus on the impact of mRNA copy number and RBS strength on the nonlinear isocline that emerges with two regimes, prominently separated by a tipping point, and study how correlation and competition dominate each other depending on various circuit parameters. Focusing further on genetic toggle circuit, we have identified major effects of resource competition in this model motif, and quantified the observations. The observations are testable in wet-lab experiments, as all the parameters chosen are experimentally relevant.

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