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Rewiring of Genetic Networks in Response to Modification of Genetic Background

Genome-scale genetic interaction networks are progressively contributing to map the molecular circuitry that determines cellular behavior. To what extent this mapping changes in response to different environmental or genetic conditions is, however, largely unknown. Here, we assembled a genetic netwo...

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Detalles Bibliográficos
Autores principales: Bajić, Djordje, Moreno-Fenoll, Clara, Poyatos, Juan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986454/
https://www.ncbi.nlm.nih.gov/pubmed/25432942
http://dx.doi.org/10.1093/gbe/evu255
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author Bajić, Djordje
Moreno-Fenoll, Clara
Poyatos, Juan F.
author_facet Bajić, Djordje
Moreno-Fenoll, Clara
Poyatos, Juan F.
author_sort Bajić, Djordje
collection PubMed
description Genome-scale genetic interaction networks are progressively contributing to map the molecular circuitry that determines cellular behavior. To what extent this mapping changes in response to different environmental or genetic conditions is, however, largely unknown. Here, we assembled a genetic network using an in silico model of metabolism in yeast to explicitly ask how separate genetic backgrounds alter network structure. Backgrounds defined by single deletions of metabolically active enzymes induce strong rewiring when the deletion corresponds to a catabolic gene, evidencing a broad redistribution of fluxes to alternative pathways. We also show how change is more pronounced in interactions linking genes in distinct functional modules and in those connections that present weak epistasis. These patterns reflect overall the distributed robustness of catabolism. In a second class of genetic backgrounds, in which a number of neutral mutations accumulate, we dominantly observe modifications in the negative interactions that together with an increase in the number of essential genes indicate a global reduction in buffering. Notably, neutral trajectories that originate considerable changes in the wild-type network comprise mutations that diminished the environmental plasticity of the corresponding metabolism, what emphasizes a mechanistic integration of genetic and environmental buffering. More generally, our work demonstrates how the specific mechanistic causes of robustness influence the architecture of multiconditional genetic interaction maps.
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spelling pubmed-49864542016-08-22 Rewiring of Genetic Networks in Response to Modification of Genetic Background Bajić, Djordje Moreno-Fenoll, Clara Poyatos, Juan F. Genome Biol Evol Research Article Genome-scale genetic interaction networks are progressively contributing to map the molecular circuitry that determines cellular behavior. To what extent this mapping changes in response to different environmental or genetic conditions is, however, largely unknown. Here, we assembled a genetic network using an in silico model of metabolism in yeast to explicitly ask how separate genetic backgrounds alter network structure. Backgrounds defined by single deletions of metabolically active enzymes induce strong rewiring when the deletion corresponds to a catabolic gene, evidencing a broad redistribution of fluxes to alternative pathways. We also show how change is more pronounced in interactions linking genes in distinct functional modules and in those connections that present weak epistasis. These patterns reflect overall the distributed robustness of catabolism. In a second class of genetic backgrounds, in which a number of neutral mutations accumulate, we dominantly observe modifications in the negative interactions that together with an increase in the number of essential genes indicate a global reduction in buffering. Notably, neutral trajectories that originate considerable changes in the wild-type network comprise mutations that diminished the environmental plasticity of the corresponding metabolism, what emphasizes a mechanistic integration of genetic and environmental buffering. More generally, our work demonstrates how the specific mechanistic causes of robustness influence the architecture of multiconditional genetic interaction maps. Oxford University Press 2014-11-27 /pmc/articles/PMC4986454/ /pubmed/25432942 http://dx.doi.org/10.1093/gbe/evu255 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Bajić, Djordje
Moreno-Fenoll, Clara
Poyatos, Juan F.
Rewiring of Genetic Networks in Response to Modification of Genetic Background
title Rewiring of Genetic Networks in Response to Modification of Genetic Background
title_full Rewiring of Genetic Networks in Response to Modification of Genetic Background
title_fullStr Rewiring of Genetic Networks in Response to Modification of Genetic Background
title_full_unstemmed Rewiring of Genetic Networks in Response to Modification of Genetic Background
title_short Rewiring of Genetic Networks in Response to Modification of Genetic Background
title_sort rewiring of genetic networks in response to modification of genetic background
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986454/
https://www.ncbi.nlm.nih.gov/pubmed/25432942
http://dx.doi.org/10.1093/gbe/evu255
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