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BMC Syst Biol. 2018 Sep 26;12(1):85. doi: 10.1186/s12918-018-0609-3.

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

Luo X1,2, Song R2,3, Acar M4,5,6,7.

Author information

1
Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT, 06511, USA.
2
Systems Biology Institute, Yale University, 850 West Campus Drive, Room 122, West Haven, CT, 06516, USA.
3
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, 300 George Street, Suite 501, New Haven, CT, 06511, USA.
4
Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT, 06511, USA. murat.acar@yale.edu.
5
Systems Biology Institute, Yale University, 850 West Campus Drive, Room 122, West Haven, CT, 06516, USA. murat.acar@yale.edu.
6
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, 300 George Street, Suite 501, New Haven, CT, 06511, USA. murat.acar@yale.edu.
7
Department of Physics, Yale University, 217 Prospect Street, New Haven, CT, 06511, USA. murat.acar@yale.edu.

Abstract

BACKGROUND:

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. 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.

RESULTS:

Here 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.

CONCLUSIONS:

These 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.

KEYWORDS:

Cell; Cell-environment interaction; Evolution; Galactose network; Gene network; Survival; Systems biology; Yeast

PMID:
30257679
PMCID:
PMC6158886
DOI:
10.1186/s12918-018-0609-3
[Indexed for MEDLINE]
Free PMC Article

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