Multi-component gene network design as a survival strategy in diverse environments

Xinyue Luo,Murat Acar,Ruijie Song

doi:10.1186/s12918-018-0609-3

Abstract

BackgroundGene-environment interactions are often mediated though gene networks in which gene expression products interact with other network components to dictate network activity levels, which in turn determines the fitness of the host cell in specific environments. Even though a gene network is the right context for studying gene-environment interactions, we have little understanding on how systematic genetic perturbations affects fitness in the context of a gene network.ResultsHere we examine the effect of combinatorial gene dosage alterations on gene network activity and cellular fitness. Using the galactose utilization pathway as a model network in diploid yeast, we reduce the copy number of four regulatory genes (GAL2, GAL3, GAL4, GAL80) from two to one, and measure the activity of the perturbed networks. We integrate these results with competitive fitness measurements made in six different rationally-designed environments containing different galactose concentrations representing the natural induction spectrum of the galactose network. In the lowest galactose environment, we find a nonlinear relationship between gene expression and fitness while high galactose environments lead to a linear relationship between the two with a saturation regime reached at a sufficiently high galactose concentration. We further uncover environment-specific relevance of the different network components for dictating the relationship between the network activity and organismal fitness, indicating that none of the network components are redundant.ConclusionsThese results provide experimental support to the hypothesis that dynamic changes in the environment throughout natural evolution is key to structuring natural gene networks in a multi-component fashion, which robustly provides protection against population extinction in different environments.

Highlights

Gene-environment interactions are often mediated though gene networks in which gene expression products interact with other network components to dictate network activity levels, which in turn determines the fitness of the host cell in specific environments
Transcription of genes in the galactose utilization (GAL) network is controlled by the constitutively expressed transcription factor Gal4p, whose activity in the absence of galactose is inhibited by the inhibitor Gal80p
The signal transducer Gal3p is activated by galactose and binds to the inhibitor Gal80p, relieving Gal4p from Gal80p’s suppression to activate all GAL network genes except for Gal4p itself [20,21,22,23]

Summary

Introduction

Gene-environment interactions are often mediated though gene networks in which gene expression products interact with other network components to dictate network activity levels, which in turn determines the fitness of the host cell in specific environments. Cells are extraordinarily complex systems that emerged out of billions of years of evolution that morphed the earliest prokaryotes into the diverse universe of biological organisms today Having undergone such a lengthy optimization process, the parameters of these systems, including the expression levels of the genes in the cell, are surely near their optimal values for fitness. It follows that, as a general matter, significant changes to such parameters will likely cause a reduction in fitness, and halving the dosage of genes generally do not interact with the environment in isolation. To study the effect of genetic perturbations without considering it in the context of the gene network is not unlike the parable of the blind men and an elephant: it misses the forest for the trees

Methods

Results

Conclusion