{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:57:58Z","timestamp":1772171878397,"version":"3.50.1"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T00:00:00Z","timestamp":1476403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005156","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T13:43:58Z","timestamp":1476452638000},"page":"e1005156","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits"],"prefix":"10.1371","volume":"12","author":[{"given":"Guillermo","family":"Rodrigo","sequence":"first","affiliation":[]},{"given":"Juan F.","family":"Poyatos","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2016,10,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1073\/pnas.94.3.814","article-title":"Stochastic mechanisms in gene expression","volume":"94","author":"HH McAdams","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1126\/science.1070919","article-title":"Stochastic gene expression in a single cell","volume":"297","author":"MB Elowitz","year":"2002","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09333","article-title":"Fundamental limits on the suppression of molecular fluctuations","volume":"467","author":"I Lestas","year":"2010","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1073\/pnas.71.10.4135","article-title":"Kinetic proofreading: A new mechanism for reducing errors in biosynthetic processes requiring high specificity","volume":"71","author":"JJ Hopfield","year":"1974","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1073\/pnas.97.9.4649","article-title":"Robust perfect adaptation in bacterial chemotaxis through integral feedback control","volume":"97","author":"TM Yi","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2958.2006.05504.x","article-title":"Phenotypic heterogeneity can enhance rare-cell survival in \u2018stress-sensitive\u2019 yeast populations","volume":"63","author":"AL Bishop","year":"2007","journal-title":"Mol Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1126\/science.1099390","article-title":"Bacterial persistence as a phenotypic switch","volume":"305","author":"NQ Balaban","year":"2004","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nature04588","article-title":"An excitable gene regulatory circuit induces transient cellular differentiation","volume":"440","author":"GM S\u00fcel","year":"2006","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/ng.110","article-title":"Stochastic switching as a survival strategy in fluctuating environments","volume":"40","author":"M Acar","year":"2008","journal-title":"Nat Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"15732","DOI":"10.1073\/pnas.0806349105","article-title":"A genetic timer through noise-induced stabilization of an unstable state","volume":"105","author":"M Turcotte","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature08781","article-title":"Variability in gene expression underlies incomplete penetrance","volume":"463","author":"A Raj","year":"2010","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1158013","article-title":"Variability and robustness in T cell activation from regulated heterogeneity in protein levels","volume":"321","author":"O Feinerman","year":"2008","journal-title":"Science"},{"key":"ref13","article-title":"Genetic homeostasis","author":"IM Lerner","year":"1954"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0168-9525(98)01659-X","article-title":"It\u2019s a noisy business! Genetic regulation at the nanomolar scale","volume":"15","author":"HH McAdams","year":"1999","journal-title":"Trends Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/40618","article-title":"Evolution of genetic redundancy","volume":"388","author":"MA Nowak","year":"1997","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.copbio.2014.05.002","article-title":"Cellular noise and information transmission","volume":"28","author":"A Levchenko","year":"2014","journal-title":"Curr Opin Biotechnol"},{"key":"ref17","first-page":"149","article-title":"Curr Opin Biotechnol","volume":"28","author":"CG Bowsher","year":"2014"},{"key":"ref18","article-title":"Elements of Information Theory","author":"TM Cover","year":"2006"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"12265","DOI":"10.1073\/pnas.0806077105","article-title":"Information flow and optimization in transcriptional regulation","volume":"105","author":"G Tkacik","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.1073\/pnas.0608963104","article-title":"Noisy information processing through transcriptional regulation","volume":"104","author":"E Libby","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nature07513","article-title":"Negative feedback that improves information transmission in yeast signalling","volume":"456","author":"RC Yu","year":"2008","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"16301","DOI":"10.1073\/pnas.1315642110","article-title":"Positional information, in bits","volume":"110","author":"JO Dubuis","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1126\/science.1204553","article-title":"Information transduction capacity of noisy biochemical signaling networks","volume":"334","author":"R Cheong","year":"2011","journal-title":"Science"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e06559","DOI":"10.7554\/eLife.06559","article-title":"Limits on information transduction through amplitude and frequency regulation of transcription factor activity","volume":"4","author":"AS Hansen","year":"2015","journal-title":"eLife"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nrg1244","article-title":"Design of gene circuits: lessons from bacteria","volume":"5","author":"ME Wall","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1103\/PhysRevE.52.4691","article-title":"Stochastic resonance and the dithering effect in threshold physical systems","volume":"52","author":"L Gammaitoni","year":"1995","journal-title":"Phys Rev E"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1209\/0295-5075\/29\/3\/001","article-title":"Non-dynamical stochastic resonance: theory and experiments with white and arbitrarily coloured noise","volume":"29","author":"Z Gingl","year":"1995","journal-title":"Europhys Lett"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1103\/RevModPhys.70.223","article-title":"Stochastic resonance","volume":"70","author":"L Gammaitoni","year":"1998","journal-title":"Rev Mod Phys"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1103\/PhysRevLett.84.2310","article-title":"Suprathreshold stochastic resonance in multilevel threshold systems","volume":"84","author":"NG Stocks","year":"2000","journal-title":"Phys Rev Lett"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"A mathematical theory of communication","volume":"27","author":"CE Shannon","year":"1948","journal-title":"Bell Syst Tech J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/bies.1045","article-title":"Wnt signalling: a theme with nuclear variations","volume":"23","author":"C Sharpe","year":"2001","journal-title":"Bioessays"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"12795","DOI":"10.1073\/pnas.162041399","article-title":"Intrinsic and extrinsic contributions to stochasticity in gene expression","volume":"99","author":"PS Swain","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"22460","DOI":"10.1016\/S0021-9258(18)41694-8","article-title":"Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun","volume":"267","author":"D Masquilier","year":"1992","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nature06151","article-title":"Gene duplication and the adaptive evolution of a classic genetic switch","volume":"449","author":"CT Hittinger","year":"2007","journal-title":"Nature"},{"key":"ref35","first-page":"555","article-title":"Plasticity of the cis-regulatory input function of a gene","volume":"4","author":"AE Mayo","year":"2006","journal-title":"PLoS Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1162\/NECO_a_00621","article-title":"The competing benefits of noise and heterogeneity in neural coding","volume":"26","author":"E Hunsberger","year":"2014","journal-title":"Neural Comput"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1186\/1471-2105-13-S4-S11","article-title":"Characterization of an inducible promoter in different DNA copy number conditions","volume":"13","author":"S Zucca","year":"2012","journal-title":"BMC bioinformatics"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.1169498","article-title":"Tuning the activation threshold of a kinase network by nested feedback loops","volume":"324","author":"QA Justman","year":"2009","journal-title":"Science"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"9392","DOI":"10.1073\/pnas.88.21.9392","article-title":"FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction","volume":"88","author":"EA Elion","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1371\/journal.pbio.0020128","article-title":"Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast","volume":"2","author":"Y Wang","year":"2004","journal-title":"PLoS Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1186\/1471-2164-15-1085","article-title":"Deciphering regulatory variation of THI genes in alcoholic fermentation indicate an impact of Thi3p on PDC1 expression","volume":"15","author":"C Brion","year":"2014","journal-title":"BMC Genomics"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrn3061","article-title":"The benefits of noise in neural systems: bridging theory and experiment","volume":"12","author":"MD McDonnell","year":"2011","journal-title":"Nat Rev Neurosci"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nature09326","article-title":"Functional roles for noise in genetic circuits","volume":"467","author":"A Eldar","year":"2010","journal-title":"Nature"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1073\/pnas.0604883103","article-title":"The regulatory utilization of genetic redundancy through responsive backup circuits","volume":"103","author":"R Kafri","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1101\/gr.176792.114","article-title":"Preservation of genetic and regulatory robustness in ancient gene duplicates of Saccharomyces cerevisiae","volume":"24","author":"OM Keane","year":"2014","journal-title":"Genome Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1073\/pnas.98.2.525","article-title":"Genetic architecture of thermal adaptation in Escherichia coli","volume":"98","author":"MM Riehle","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"e1000303","DOI":"10.1371\/journal.pgen.1000303","article-title":"The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast","volume":"4","author":"D Gresham","year":"2008","journal-title":"PLoS Genet"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.cell.2010.11.021","article-title":"Functional overlap and regulatory links shape genetic interactions between signaling pathways","volume":"143","author":"S van Wageningen","year":"2010","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nature04281","article-title":"Origins of extrinsic variability in eukaryotic gene expression","volume":"439","author":"D Volfson","year":"2006","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1126\/science.1254933","article-title":"Accurate information transmission through dynamic biochemical signaling networks","volume":"346","author":"J Selimkhanov","year":"2014","journal-title":"Science"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1126\/science.1234511","article-title":"Robustness and compensation of information transmission of signaling pathways","volume":"341","author":"S Uda","year":"2013","journal-title":"Science"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.tree.2005.05.008","article-title":"Consensus decision making in animals","volume":"20","author":"L Conradt","year":"2005","journal-title":"Trends Ecol Evol"},{"key":"ref53","article-title":"Probabilistic logics and the synthesis of reliable organisms from unreliable components","author":"J von Neumann","year":"1956"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0016-0032(56)90559-2","article-title":"Reliable circuits using less reliable relays","volume":"262","author":"EF Moore","year":"1956","journal-title":"J Franklin I"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nbt1308","article-title":"Engineering synthetic signaling proteins with ultrasensitive input\/output control","volume":"25","author":"JE Dueber","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1063\/1.481811","article-title":"The chemical Langevin equation","volume":"113","author":"D Gillespie","year":"2000","journal-title":"J Chem Phys"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"025109","DOI":"10.1063\/1.4809786","article-title":"Theoretical and experimental analysis of the forced LacI-AraC oscillator with a minimal gene regulatory model","volume":"23","author":"G Rodrigo","year":"2013","journal-title":"Chaos"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nature04588","article-title":"An excitable gene regulatory circuit induces transient cellular differentiation","volume":"440","author":"G S\u00fcel","year":"2006","journal-title":"Nature"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e1002480","DOI":"10.1371\/journal.pcbi.1002480","article-title":"Mapping the environmental fitness landscape of a synthetic gene circuit","volume":"8","author":"D Nevozhay","year":"2012","journal-title":"PLoS Comp Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1126\/science.1192588","article-title":"Interdependence of cell growth and gene expression: origins and consequences","volume":"330","author":"M Scott","year":"2010","journal-title":"Science"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T07:49:03Z","timestamp":1657439343000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005156"}},"subtitle":[],"editor":[{"given":"Alexandre V","family":"Morozov","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2016,10,14]]},"references-count":60,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005156","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/040931","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,14]]}}}