A General Mechanism for Network-Dosage Compensation in Gene Circuits
Coping with variations in network dosage is crucial for maintaining optimal function in gene networks. We explored how network structure facilitates network-level dosage compensation. By using the yeast galactose network as a model, we combinatorially deleted one of the two copies of its four regulatory genes and found that network activity was robust to the change in network dosage. A mathematical analysis revealed that a two-component genetic circuit with elements of opposite regulatory activity (activator and inhibitor) constitutes a minimal requirement for network-dosage invariance. Specific interaction topologies and a one-to-one interaction stoichiometry between the activating and inhibiting agents were additional essential elements facilitating dosage invariance. This mechanism of network-dosage invariance could represent a general design for gene network structure in cells.
Additional Information© 2010 American Association for the Advancement of Science. Received 6 April 2010; accepted 9 August 2010. The authors would like to thank J. J. Collins, M. Thattai, and H. Youk for helpful discussions and/or comments on the manuscript. M.A. was supported by a fellowship grant from the Center for Biological Circuit Design at Caltech. B.F.P. and A.v.O were supported by grants from NIH and NSF. Work in the Elowitz laboratory was supported by the Packard Foundation, NSF, and NIH. Work in the Arnold laboratory was supported by NIH.
Accepted Version - nihms303988.pdf
Supplemental Material - 1.pdf