Goetz Hanah, Zhang Rong, Wang Xiao, Tian Xiao-Jun
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States of America.
PLoS Comput Biol. 2025 Apr 23;21(4):e1012931. doi: 10.1371/journal.pcbi.1012931. eCollection 2025 Apr.
Although the impact of resource competition on the deterministic behavior of synthetic gene circuits has been studied, its effects on gene expression noise remain obscure. In this work, we systematically analyze the role of resource competition in noise propagation within a genetic inhibition cascade circuit. We found that resource competition amplifies gene expression noise by introducing unexpected bistability and stochastic switching between the two stable states. This emergent bistability, driven by resource competition-mediated double negative feedback, allows one gene to dominate expression while suppressing the other in a "winner-takes-all" behavior. Our findings highlight the critical role of resource competition in shaping the noise dynamics and its propagation, underscoring the importance of considering these effects when designing and controlling synthetic circuits.
尽管资源竞争对合成基因回路确定性行为的影响已得到研究，但其对基因表达噪声的影响仍不清楚。在这项工作中，我们系统地分析了资源竞争在遗传抑制级联回路噪声传播中的作用。我们发现，资源竞争通过引入意外的双稳态以及在两个稳定状态之间的随机切换来放大基因表达噪声。这种由资源竞争介导的双负反馈驱动的新兴双稳态，使得一个基因在“赢家通吃”的行为中主导表达，同时抑制另一个基因。我们的研究结果突出了资源竞争在塑造噪声动态及其传播中的关键作用，强调了在设计和控制合成回路时考虑这些影响的重要性。
