The Molecular Mechanism of a Cis-Regulatory Adaptation in Yeast

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dc.contributor.authorChang, Jessica
dc.contributor.authorZhou, Yiqi
dc.contributor.authorHu, Xiaoli
dc.contributor.authorLam, Lucia
dc.contributor.authorHenry, Cameron
dc.contributor.authorGreen, Erin
dc.contributor.authorKita, Ryosuke
dc.contributor.authorKobor, Michael S.
dc.contributor.authorFraser, Hunter B.
dc.date.accessioned2023-01-25T20:48:33Z
dc.date.available2023-01-25T20:48:33Z
dc.date.issued2013-09-19
dc.description.abstractDespite 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.en_US
dc.description.urihttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003813en_US
dc.format.extent8 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m29kde-zp76
dc.identifier.citationChang, Jessica et al. “The molecular mechanism of a cis-regulatory adaptation in yeast.” PLoS genetics vol. 9,9 (2013): e1003813. doi:10.1371/journal.pgen.1003813en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pgen.1003813
dc.identifier.urihttp://hdl.handle.net/11603/26715
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.titleThe Molecular Mechanism of a Cis-Regulatory Adaptation in Yeasten_US
dc.typeTexten_US
dcterms.creatorhttps://orcid.org/0000-0003-3923-6726en_US

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