Rewiring of genetic networks in response to modification of genetic background

BioRxiv : the Preprint Server for Biology
Djordje BajićJuan F Poyatos


Genome-scale genetic interaction networks are progressively contributing to map the molecular circuitry that determines cellular behaviour. 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 t...Continue Reading

Related Concepts

Epistasis, Genetic
Gene Deletion
Genetic Techniques
Drug Interactions

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