Related Experiment Video
Updated: Jun 7, 2025

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli
Published on: March 16, 2011
Phenotype selection due to mutational robustness
1Cybermedia Center, Osaka University, Toyonaka, Japan.
Abstract:
The mutation-selection mechanism of Darwinian evolution gives rise not only to adaptation to environmental conditions but also to the enhancement of robustness against mutations. When two or more phenotypes have the same fitness value, the robustness distribution for different phenotypes can vary. Thus, we expect that some phenotypes are favored in evolution and that some are hardly selected because of a selection bias for mutational robustness. In this study, we investigated this selection bias for phenotypes in a model of gene regulatory networks (GRNs) using numerical simulations. The model had one input gene accepting a signal from the outside and one output gene producing a target protein, and the fitness was high if the output for the full signal was much higher than that for no signal. The model exhibited three types of responses to changes in the input signal: monostable, toggle switch, and one-way switch. We regarded these three response types as three distinguishable phenotypes. We constructed a randomly generated set of GRNs using the multicanonical Monte Carlo method originally developed in statistical physics and compared it to the outcomes of evolutionary simulations. One-way switches were strongly suppressed during evolution because of their lack of mutational robustness. By examining one-way switch GRNs in detail, we found that mutationally robust GRNs obtained by evolutionary simulations and non-robust GRNs obtained by McMC have different network structures. While robust GRNs have a common core motif, non-robust GRNs lack this motif. The bistability of non-robust GRNs is considered to be realized cooperatively by many genes, and these cooperative genotypes have been suppressed by evolution.
Related Concept Videos
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Types of Selection
Frequency-dependent Selection
Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
Mutation, Gene Flow, and Genetic Drift
Complementation Tests
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...

