ArticleProceedings of the National Academy of Sciences of the United States of America2007
Plasticity of genetic interactions in metabolic networks of yeast.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed.
- Article
- Minimisation of metabolic networks defines a new functional class of genes.Nature communications · 2024Article
- Selection for robust metabolism in domesticated yeasts is driven by adaptation to Hsp90 stress.Science (New York, N.Y.) · 2024Article
- Article
- Genome-scale model ofMicrobiology spectrum · 2024Article
- Natural Product Synthesis in the 21st Century: Beyond the Mountain Top.ACS central science · 2024Review
- Functional compensation of mouse duplicates by their paralogs expressed in the same tissues.Genome biology and evolution · 2022Article
- Discovery of synthetic lethal and tumor suppressor paralog pairs in the human genome.Cell reports · 2021Article
- Bacterial fitness landscapes stratify based on proteome allocation associated with discrete aero-types.PLoS computational biology · 2021Article
- SNPeffect: identifying functional roles of SNPs using metabolic networks.The Plant journal : for cell and molecular biology · 2020Article
- Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism.Nature metabolism · 2020Article
- Genome-Scale Metabolic Reconstruction andBiology · 2020Article
- Changes in gene expression predictably shift and switch genetic interactions.Nature communications · 2019Article
- Flux balance analysis with or without molecular crowding fails to predict two thirds of experimentally observed epistasis in yeast.Scientific reports · 2019Article
- Modelling approaches for studying the microbiome.Nature microbiology · 2019Review
- Review
- Evolutionary design principles in metabolism.Proceedings. Biological sciences · 2019Review
- Article
- Understanding the evolution of functional redundancy in metabolic networks.Bioinformatics (Oxford, England) · 2018Article
- Interdependence of Primary Metabolism and Xenobiotic Mitigation Characterizes the Proteome of Bjerkandera adusta during Wood Decomposition.Applied and environmental microbiology · 2018Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
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.
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