Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Nonlinear dynamics in gene regulation promote robustness and evolvability of gene expression levels

Tools
- Tools
+ Tools

Steinacher, Arno, Bates, Declan, Akman, Ozgur E. and Soyer, Orkun S. (2016) Nonlinear dynamics in gene regulation promote robustness and evolvability of gene expression levels. PLoS One, 11 (4). e0153295. doi:10.1371/journal.pone.0153295

[img]
Preview
PDF
WRAP_journal.pone.0153295.PDF - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (4Mb) | Preview
Official URL: http://dx.doi.org/10.1371/journal.pone.0153295

Request Changes to record.

Abstract

Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability) under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest an explanation for the ubiquity of nonlinear dynamics in gene expression networks, and generate useful guidelines for the design of synthetic gene circuits.

Item Type: Journal Article
Subjects: Q Science > QA Mathematics
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH): Gene regulatory networks -- Mathematical models, Mutation (Biology) , Genetics, Phenotype, Evolution equations, Nonlinear
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 15 April 2016
Dates:
DateEvent
15 April 2016Published
28 March 2016Accepted
13 April 2015Submitted
Volume: 11
Number: 4
Article Number: e0153295
DOI: 10.1371/journal.pone.0153295
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Engineering and Physical Sciences Research Council (EPSRC)
Grant number: EP/I017445/1

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us