ArticlePLoS genetics2013
The molecular mechanism of a cis-regulatory adaptation in yeast.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 43 citations in OpenAlex.
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Existing methods are effective at measuring natural selection on gene expression.Nature ecology & evolution · 2022Article
- Divergent patterns of selection on metabolite levels and gene expression.BMC ecology and evolution · 2021Article
- Uncovering Divergence in Gene Expression Regulation in the Adaptation of Yeast to Nitrogen Scarcity.mSystems · 2021Article
- Molecular and evolutionary processes generating variation in gene expression.Nature reviews. Genetics · 2021Review
- Lineage-specific selection and the evolution of virulence in theProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Systematic identification ofeLife · 2020Article
- DNA variants affecting the expression of numerous genes in trans have diverse mechanisms of action and evolutionary histories.PLoS genetics · 2019Article
- Review
- Evolution of substrate-specific gene expression and RNA editing in brown rot wood-decaying fungi.The ISME journal · 2019Article
- Transposable element insertions shape gene regulation and melanin production in a fungal pathogen of wheat.BMC biology · 2018Article
- Linkage mapping of yeast cross protection connects gene expression variation to a higher-order organismal trait.PLoS genetics · 2018Article
- Functional characterization of adaptive variation within a cis-regulatory element influencing Drosophila melanogaster growth.PLoS biology · 2018Article
- High-resolution mapping ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Regulation of gene expression and RNA editing in Drosophila adapting to divergent microclimates.Nature communications · 2017Article
- Genetic basis of mycotoxin susceptibility differences between budding yeast isolates.Scientific reports · 2017Article
- Cis-regulatory evolution in prokaryotes revealed by interspecific archaeal hybrids.Scientific reports · 2017Article
- Cis-Regulatory Divergence in Gene Expression between Two Thermally Divergent Yeast Species.Genome biology and evolution · 2017Article
- Natural variation in non-coding regions underlying phenotypic diversity in budding yeast.Scientific reports · 2016Article
- Dissecting the Genetic Basis of a Complex cis-Regulatory Adaptation.PLoS genetics · 2015Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite recent advances in our ability to detect adaptive evolution involving the cis-regulation of gene expression, our knowledge of the molecular mechanisms underlying these adaptations has lagged far behind. Across all model organisms, the causal mutations have been discovered for only a handful of gene expression adaptations, and even for these, mechanistic details (e.g. the trans-regulatory factors involved) have not been determined. We previously reported a polygenic gene expression adaptation involving down-regulation of the ergosterol biosynthesis pathway in the budding yeast Saccharomyces cerevisiae. Here we investigate the molecular mechanism of a cis-acting mutation affecting a member of this pathway, ERG28. We show that the causal mutation is a two-base deletion in the promoter of ERG28 that strongly reduces the binding of two transcription factors, Sok2 and Mot3, thus abolishing their regulation of ERG28. This down-regulation increases resistance to a widely used antifungal drug targeting ergosterol, similar to mutations disrupting this pathway in clinical yeast isolates. The identification of the causal genetic variant revealed that the selection likely occurred after the deletion was already present at high frequency in the population, rather than when it was a new mutation. These results provide a detailed view of the molecular mechanism of a cis-regulatory adaptation, and underscore the importance of this view to our understanding of evolution at the molecular level.
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