Plasticity of genetic interactions in metabolic networks of yeast

Richard Harrison, Balázs Papp, Csaba Pál, Stephen G. Oliver, Daniela Delneri

    Research output: Contribution to journalArticlepeer-review


    Why are most genes dispensable? The impact of gene deletions may depend on the environment (plasticity), the presence of compensatory mechanisms (mutational robustness), or both. Here, we analyze the interaction between these two forces by exploring the condition-dependence of synthetic genetic interactions that define redundant functions and alternative pathways. We performed systems-level flux balance analysis of the yeast (Saccharomyces cerevisiae) metabolic network to identify genetic interactions and then tested the model's predictions with in vivo gene-deletion studies. We found that the majority of synthetic genetic interactions are restricted to certain environmental conditions, partly because of the lack of compensation under some (but not all) nutrient conditions. Moreover, the phylogenetic cooccurrence of synthetically interacting pairs is not significantly different from random expectation. These findings suggest that these gene pairs have at least partially independent functions, and, hence, compensation is only a byproduct of their evolutionary history. Experimental analyses that used multiple gene deletion strains not only confirmed predictions of the model but also showed that investigation of false predictions may both improve functional annotation within the model and also lead to the discovery of higher-order genetic interactions. Our work supports the view that functional redundancy may be more apparent than real, and it offers a unified framework for the evolution of environmental adaptation and mutational robustness. © 2007 by The National Academy of Sciences of the USA.
    Original languageEnglish
    Pages (from-to)2307-2312
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number7
    Publication statusPublished - 13 Feb 2007


    • Environmental dependence
    • Epistasis
    • Flux balance analysis
    • Genetic robustness
    • Saccharomyces cerevisiae


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