ArticleNature communications2019
Harmonious genetic combinations rewire regulatory networks and flip gene essentiality.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks.Science advances · 2023Article
- Robustness and innovation in synthetic genotype networks.Nature communications · 2023Article
- Challenges and potential solutions for studying the genetic and phenotypic architecture of adaptation in microbes.Current opinion in genetics & development · 2022Review
- Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers.Nature communications · 2021Article
- The complex role of genetic background in shaping the effects of spontaneous and induced mutations.Yeast (Chichester, England) · 2021Review
- Article
- A parallelized strategy for epistasis analysis based on Empirical Bayesian Elastic Net models.Bioinformatics (Oxford, England) · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We lack an understanding of how the full range of genetic variants that occur in individuals can interact. To address this shortcoming, here we combine diverse mutations between genes in a model regulatory network, the galactose (GAL) switch of budding yeast. The effects of thousands of pairs of mutations fall into a limited number of phenotypic classes. While these effects are mostly predictable using simple rules that capture the 'stereotypical' genetic interactions of the network, some double mutants have unexpected outcomes including constituting alternative functional switches. Each of these 'harmonious' genetic combinations exhibits altered dependency on other regulatory genes. These cases illustrate how both pairwise and higher epistasis determines gene essentiality and how combinations of mutations rewire regulatory networks. Together, our results provide an overview of how broad spectra of mutations interact, how these interactions can be predicted, and how diverse genetic solutions can achieve 'wild-type' phenotypic behavior.
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Registered trials
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