title: Isocost Lines Describe the Cellular Economy of Genetic Circuits.
abstract: Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings.
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Andras
authors.initials: A
authors.lastname: Gyorgy
authors.affiliation: Faculty of Health of Medical Sciences, University of Surrey, Guildford, UK; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: José I
authors.initials: JI
authors.lastname: Jiménez
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Yazbek
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Hsin-Ho
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hattie
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: ddv@mit.edu.
authors.forename: Domitilla
authors.initials: D
authors.lastname: Del Vecchio
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D012270:Ribosomes / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins