Bistability in feedback circuits as a byproduct of evolution of evolvability

Molecular Systems Biology
Hiroyuki Kuwahara, Orkun S Soyer


Noisy bistable dynamics in gene regulation can underlie stochastic switching and is demonstrated to be beneficial under fluctuating environments. It is not known, however, if fluctuating selection alone can result in bistable dynamics. Using a stochastic model of simple feedback networks, we apply fluctuating selection on gene expression and run in silico evolutionary simulations. We find that independent of the specific nature of the environment-fitness relationship, the main outcome of fluctuating selection is the evolution of increased evolvability in the network; system parameters evolve toward a nonlinear regime where phenotypic diversity is increased and small changes in genotype cause large changes in expression level. In the presence of noise, the evolution of increased nonlinearity results in the emergence and maintenance of bistability. Our results provide the first direct evidence that bistability and stochastic switching in a gene regulatory network can emerge as a mechanism to cope with fluctuating environments. They strongly suggest that such emergence occurs as a byproduct of evolution of evolvability and exploitation of noise by evolution.


Dec 4, 2012·Microbiology and Molecular Biology Reviews : MMBR·Wai Ting ChanManuel Espinosa
Jul 5, 2013·BMC Systems Biology·Gaël YvertYoshikazu Ohya
Apr 10, 2013·Current Opinion in Biotechnology·K A Geiler-SamerotteMark L Siegal
May 21, 2013·Cell Biology International·Vasily V GrinevSergey V Gloushen
May 18, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Orkun S Soyer, Maureen A O'Malley
Mar 3, 2015·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Manfred Drack
Apr 30, 2013·The FEBS Journal·Olaf Wolkenhauer, Sara Green
Jul 15, 2015·International Journal of Food Microbiology·A BridierR Briandet
Apr 23, 2015·Molecular Microbiology·Jeanette HahnDavid Dubnau
Mar 19, 2014·Current Opinion in Plant Biology·Cynthia WeinigStephen M Welch
Feb 11, 2015·Current Opinion in Microbiology·Bruno M C Martins, James C W Locke
Jul 28, 2016·Cell Systems·Oguzhan AtayJan M Skotheim
Dec 21, 2016·Journal of Theoretical Biology·Farzaneh Maleki, Attila Becskei
Nov 14, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Hiroyuki KuwaharaXin Gao
Aug 16, 2017·Physical Chemistry Chemical Physics : PCCP·Anna Ochab-MarcinekMarcin Tabaka
May 11, 2016·PLoS Computational Biology·Song FengOrkun S Soyer
Mar 1, 2017·BMC Evolutionary Biology·Thomas D CuypersPaulien Hogeweg
Jun 19, 2015·Biological Theory·Maureen A O'MalleyMark L Siegal
Oct 29, 2019·PLoS Computational Biology·Mariana Gómez-Schiavon, Nicolas E Buchler


Sep 1, 1966·Journal of Theoretical Biology·D Cohen
Feb 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·G K AckersM A Shea
Feb 5, 2000·Nature·T S GardnerJ J Collins
Nov 15, 2002·Nature·Christopher V RaoAdam P Arkin
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Farren J IsaacsJ J Collins
Feb 20, 2004·Nature·Ertugrul M OzbudakAlexander van Oudenaarden
May 29, 2004·Genetics·Mukund Thattai, Alexander van Oudenaarden
Jul 20, 2004·Clinical Microbiology Reviews·Marjan W van der Woude, Andreas J Bäumler
Aug 17, 2004·Science·Nathalie Q BalabanStanislas Leibler
Nov 30, 2004·Nature Genetics·Amir AharoniDan S Tawfik
Dec 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Tatsuo Shibata, Koichi Fujimoto
Feb 3, 2005·Journal of Bacteriology·Masaya FujitaRichard Losick
Feb 3, 2005·Genetics·Edo KussellStanislas Leibler
May 13, 2005·Nature·Murat AcarAlexander van Oudenaarden
Sep 24, 2005·Science·Jonathan M Raser, Erin K O'Shea
Jul 15, 1957·Proceedings of the National Academy of Sciences of the United States of America·A Novick, M Weiner
Aug 2, 2006·Molecular Microbiology·David Dubnau, Richard Losick
Oct 14, 2006·Annual Review of Physical Chemistry·Daniel T Gillespie
Dec 21, 2006·Science's STKE : Signal Transduction Knowledge Environment·Michael S SamoilovAdam P Arkin
Dec 26, 2006·Molecular Cell·William J BlakeJames J Collins
May 26, 2007·Science·Christian R LandryDaniel L Hartl
Jun 16, 2007·Science·Hédia MaamarDavid Dubnau
Jun 26, 2007·PLoS Computational Biology·Milan van Hoek, Paulien Hogeweg
Jul 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kevin F MurphyJames J Collins
Aug 19, 2007·PLoS Biology·Cynthia C SteinerHopi E Hoekstra
Sep 7, 2007·PLoS Biology·Benjamin B KaufmannAlexander van Oudenaarden
Nov 10, 2007·Physical Biology·Mohammad Sedighi, Anirvan M Sengupta
Mar 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jan-Willem VeeningLeendert W Hamoen
Mar 26, 2008·Nature Genetics·Murat AcarAlexander van Oudenaarden
Apr 5, 2008·Science·Richard Losick, Claude Desplan
Jul 2, 2008·Nature Reviews. Genetics·Luis López-MauryJürg Bähler
Jul 12, 2008·PLoS Computational Biology·Anton Crombach, Paulien Hogeweg
Aug 22, 2008·PLoS Computational Biology·Sorin Tănase-Nicola, Pieter Rein ten Wolde
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Mar 5, 2009·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Andre S Ribeiro
May 29, 2009·Genetics·Marcel SalathéMarcus W Feldman
Aug 20, 2009·Molecular Systems Biology·Zhihua ZhangJianzhi Zhang
Nov 6, 2009·Nature·Hubertus J E BeaumontPaul B Rainey
Dec 4, 2009·PLoS Biology·Sijmen E SchoustraRees Kassen

Related Concepts

In Silico
Stochastic Processes
Genomic Stability
Gene-Environment Interaction
Biological Adaptation
Gene Expression
Gene Regulatory Networks
Feedback, Biochemical
Impacts, Environmental
Genotype Determination

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.