Bistability in feedback circuits as a byproduct of evolution of evolvability

Molecular Systems Biology

Hiroyuki Kuwahara¹ 

[1] The Ray and Stephanie Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA

关键词: environmental fluctuations;    gene regulatory network;    noise;    phenotypic variability;    stochastic switching;   

DOI  :  10.1038/msb.2011.98

来源: Wiley

【 摘 要 】

Abstract

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.

Synopsis

Simulations of the evolution of simple gene regulatory networks reveal that fluctuating environmental selection can lead to the emergence of bistability under certain conditions where fluctuation and mutational rates are in tune.

• Bistability-mediated stochastic switching is observed in many microbial phenotypes. While experimental and theoretical work has shown population-level fitness benefits of this phenomenon under fluctuating environments, it is not known if and how fluctuating selection can result in incremental evolution of bistability at single cell level.
• Using a stochastic model of a simple network and in silico evolution, we study the effect of fluctuating selection on gene expression dynamics. Under intermediary fluctuation rates, we find evolution of evolvability and reduced adaptation time.
• Increased evolvability is underlined by system parameters evolving toward a nonlinear regime where phenotypic diversity is increased and small changes in genotype cause large changes in expression level.
• Only under noisy dynamics, the evolution of increased nonlinearity results in the emergence and maintenance of bistability. These results provide evidence for bistability emerging under fluctuating selection and that such emergence occurs as a byproduct of evolution of evolvability.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.