{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:00:08Z","timestamp":1790031608064,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010692","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007915","name":"Wine Australia","doi-asserted-by":"publisher","award":["AWRI 1701-3.2.2"],"award-info":[{"award-number":["AWRI 1701-3.2.2"]}],"id":[{"id":"10.13039\/501100007915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Copper tolerance and SO<jats:sub>2<\/jats:sub> tolerance are two well-studied phenotypic traits of <jats:italic>Saccharomyces cerevisiae<\/jats:italic>. The genetic bases of these traits are the allelic expansion at the <jats:italic>CUP1<\/jats:italic> locus and reciprocal translocation at the <jats:italic>SSU1<\/jats:italic> locus, respectively. Previous work identified a negative association between SO<jats:sub>2<\/jats:sub> and copper tolerance in <jats:italic>S<\/jats:italic>. <jats:italic>cerevisiae<\/jats:italic> wine yeasts. Here we probe the relationship between SO<jats:sub>2<\/jats:sub> and copper tolerance and show that an increase in <jats:italic>CUP1<\/jats:italic> copy number does not always impart copper tolerance in <jats:italic>S<\/jats:italic>. <jats:italic>cerevisiae<\/jats:italic> wine yeast. Bulk-segregant QTL analysis was used to identify variance at <jats:italic>SSU1<\/jats:italic> as a causative factor in copper sensitivity, which was verified by reciprocal hemizygosity analysis in a strain carrying 20 copies of <jats:italic>CUP1<\/jats:italic>. Transcriptional and proteomic analysis demonstrated that <jats:italic>SSU1<\/jats:italic> over-expression did not suppress <jats:italic>CUP1<\/jats:italic> transcription or constrain protein production and provided evidence that <jats:italic>SSU1<\/jats:italic> over-expression induced sulfur limitation during exposure to copper. Finally, an <jats:italic>SSU1<\/jats:italic> over-expressing strain exhibited increased sensitivity to moderately elevated copper concentrations in sulfur-limited medium, demonstrating that <jats:italic>SSU1<\/jats:italic> over-expression burdens the sulfate assimilation pathway. Over-expression of <jats:italic>MET 3\/14\/16<\/jats:italic>, genes upstream of H<jats:sub>2<\/jats:sub>S production in the sulfate assimilation pathway increased the production of SO<jats:sub>2<\/jats:sub> and H<jats:sub>2<\/jats:sub>S but did not improve copper sensitivity in an <jats:italic>SSU1<\/jats:italic> over-expressing background. We conclude that copper and SO<jats:sub>2<\/jats:sub> tolerance are conditional traits in <jats:italic>S<\/jats:italic>. <jats:italic>cerevisiae<\/jats:italic> and provide evidence of the metabolic basis for their mutual exclusivity. These findings suggest an evolutionary driver for the extreme amplification of <jats:italic>CUP1<\/jats:italic> observed in some yeasts.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010692","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T17:59:26Z","timestamp":1680026366000},"page":"e1010692","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["SO2 and copper tolerance exhibit an evolutionary trade-off in Saccharomyces cerevisiae"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-3093","authenticated-orcid":true,"given":"Cristobal A.","family":"Onetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz 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