Quantitative understanding of molecular competition as a hidden layer of gene regulatory network

Abstract

16Molecular competition is ubiquitous, essential and multifunctional throughout diverse 17 biological processes. Competition brings about trade-offs of shared limited resources 18 among the cellular components, and it thus introduce a hidden layer of regulatory 19 mechanism by connecting components even without direct physical interactions. By 20 abstracting the analogous competition mechanism behind diverse molecular systems, 21we built a unified coarse-grained competition motif model to systematically compare 22 experimental evidences in these processes and analyzed general properties shared 23 behind them. We could predict in what molecular environments competition would 24 reveal threshold behavior or display a negative linear dependence. We quantified how 25 2 competition can shape regulator-target dose-response curve, modulate dynamic 26 response speed, control target expression noise, and introduce correlated fluctuations 27 between targets. This work uncovered the complexity and generality of molecular 28 competition effect, which might act as a hidden regulatory mechanism with multiple 29 functions throughout biological networks in both natural and synthetic systems. 30 31 Keywords 32 systems biology, computational modelling, molecular competition regulation, synthetic 33 biology, network motif 34 35 4