Functional tunability of biological circuits from tinkers

In many complex regulatory networks with interlinked feedback loops, the simple core circuits are sufficient to achieve specific biological functions of the entire networks, naturally raising a question: what is the role of the additional feedback loops. Here, by investigating auto-activation and activator-repressor circuits, two most common functional motifs in regulatory networks, we show that the toggle switch acts as a tinker to elaborate the dynamical behavior of both circuits. Specifically, the additional loop does not significantly affect the stable states of the auto-activation circuit but can tune the stimulation threshold for switch (i.e., the minimal stimulus required to switch the system from the low to the high state). For the activator- repressor circuit, the tinker can tune the stimulation threshold for oscillation (i.e., the bifurcation point to generate oscillations) as well as the oscillation frequency but does not change the oscillation amplitude. These detailed results not only provide guidelines to the engineering of both synthetic circuits but also imply a significant fact that additional loops of the core circuit in a complex network are not really redundant but play a role of tuning the network´s function.