title: Environmental selection of the feed-forward loop circuit in gene-regulation networks.
abstract: Gene-regulation networks contain recurring elementary circuits termed network motifs. It is of interest to understand under which environmental conditions each motif might be selected. To address this, we study one of the most significant network motifs, a three-gene circuit called the coherent feed-forward loop (FFL). The FFL has been demonstrated theoretically and experimentally to perform a basic information-processing function: it shows a delay following ON steps of an input inducer, but not after OFF steps. Here, we ask under what environmental conditions might the FFL be selected over simpler gene circuits, based on this function. We employ a theoretical cost-benefit analysis for the selection of gene circuits in a given environment. We find conditions that the environment must satisfy in order for the FFL to be selected over simpler circuits: the FFL is selected in environments where the distribution of the input pulse duration is sufficiently broad and contains both long and short pulses. Optimal values of the biochemical parameters of the FFL circuit are determined as a function of the environment such that the delay in the FFL blocks deleterious short pulses of induction. This approach can be generally used to study the evolutionary selection of other network motifs.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Dekel
authors.forename: Shmoolik
authors.initials: S
authors.lastname: Mangan
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D020816:Amino Acid Motifs; D001671:Biochemistry / Q000379:methods; D001703:Biophysics / Q000379:methods*; D003362:Cost-Benefit Analysis; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008954:Models, Biological; D015233:Models, Statistical; D025941:Protein Interaction Mapping; D049490:Systems Biology / Q000379:methods; D014158:Transcription, Genetic
chemical_list: D029968:Escherichia coli Proteins