Nov 30, 2014

Rewiring of genetic networks in response to modification of genetic background

Genome Biology and Evolution
Djordje BajićJuan F Poyatos


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 ...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
Biochemical Pathway
Enzymes, antithrombotic
Gene Deletion Abnormality
Catabolic Process
Metabolic Pathway
Deletion Mutation
Enzymes for Treatment of Wounds and Ulcers
Enzymes, hematological

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