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Regulation by competition: a hidden layer of gene regulatory network |
Lei Wei1,2, Ye Yuan1,2, Tao Hu1,2, Shuailin Li3, Tianrun Cheng1,2, Jinzhi Lei4, Zhen Xie1,2, Michael Q. Zhang1,2,5,6, Xiaowo Wang1,2( ) |
1. Ministry of Education Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Department of Automation, Tsinghua University, Beijing 100084, China 2. Beijing National Research Center for Information Science and Technology, Beijing 100084, China 3. School of Life Sciences, Tsinghua University, Beijing 100084, China 4. Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China 5. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China 6. Department of Biological Sciences, Center for Systems Biology, The University of Texas, Richardson, TX 75080-3021, USA |
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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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Keywords
systems biology
computational modeling
molecular competition regulation
synthetic biology
network motif
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Corresponding Author(s):
Xiaowo Wang
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Online First Date: 25 January 2019
Issue Date: 30 May 2019
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