Abstract
Background
Molecular competition brings about trade-offs of shared limited resources among the cellular components, and thus introduces a hidden layer of regulatory mechanism by connecting components even without direct physical interactions. Several molecular competition scenarios have been observed recently, but there is still a lack of systematic quantitative understanding to reveal the essence of molecular competition.
Methods
Here, by abstracting the analogous competition mechanism behind diverse molecular systems, we built a unified coarse-grained competition motif model to systematically integrate experimental evidences in these processes and analyzed general properties shared behind them from steady-state behavior to dynamic responses.
Results
We could predict in what molecular environments competition would reveal threshold behavior or display a negative linear dependence. We quantified how competition can shape regulator-target dose-response curve, modulate dynamic response speed, control target expression noise, and introduce correlated fluctuations between targets.
Conclusions
This work uncovered the complexity and generality of molecular competition effect as a hidden layer of gene regulatory network, and therefore provided a unified insight and a theoretical framework to understand and employ competition in both natural and synthetic systems.
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Acknowledgements
This work has been supported by the National Natural Science Foundation of China (Nos. 61773230, 31371341, 61721003, 91730301, 31671384 and 91729301), National Basic Research Program of China (2017YFA0505503), Initiative Scientific Research Program (No. 20141081175) and Cross-discipline Foundation of Tsinghua University, and the Open Research Fund of State Key Laboratory of Bioelectronics Southeast University.
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Author summary: Competition for limited resources is ubiquitous in biological processes, playing as a hidden regulatory mechanism with diverse functions. We built a unified coarse-grained competition motif model to quantitatively understand and predict diverse phenomena mediated by molecular competition. We systematically analyzed the properties of competing regulation from steady-state behavior to dynamic responses, evaluating how competition introduces indirect regulations and constraints among the targets and how the existence of competitors could influence regulator-target response. These properties provide new insights to understand natural biological systems, and can help to predict and refine the performance of synthetic gene circuits.
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Wei, L., Yuan, Y., Hu, T. et al. Regulation by competition: a hidden layer of gene regulatory network. Quant Biol 7, 110–121 (2019). https://doi.org/10.1007/s40484-018-0162-5
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DOI: https://doi.org/10.1007/s40484-018-0162-5