Shaping Robust System through Evolution

TL;DR

This paper investigates how developmental noise influences the robustness of gene regulatory networks to both genetic mutations and environmental noise, revealing a fundamental relationship akin to physical fluctuation-dissipation principles.

Contribution

It demonstrates that a certain level of gene expression noise is essential for evolving robustness to mutations and noise, establishing a universal relationship between phenotypic variances.

Findings

Gene expression noise is necessary for robustness.

A universal variance relationship akin to fluctuation-dissipation is derived.

Developmental and mutational robustness are interconnected.

Abstract

Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness function. Through simulations of the network that undergoes mutation and selection, we show that a certain level of noise in gene expression is required for the network to acquire both types of robustness. The results reveal how the noise that cells encounter during development shapes any network's robustness, not only to noise but also to mutations. We also establish a relationship between developmental and mutational robustness through phenotypic variances caused by genetic variation and epigenetic noise. A universal relationship between the two variances is derived, akin to the fluctuation-dissipation relationship known in physics.