title: Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters.
abstract: Recent studies have shown a surprising phenomenon, whereby orthologous regulatory regions from different species drive similar expression levels despite being highly diverged in sequence. Here, we investigated this phenomenon by genomically integrating hundreds of ribosomal protein (RP) promoters from nine different yeast species into S. cerevisiae and accurately measuring their activity. We found that orthologous RP promoters have extreme expression conservation even across evolutionarily distinct yeast species. Notably, our measurements reveal two distinct mechanisms that underlie this conservation and which act in different regions of the promoter. In the core promoter region, we found compensatory changes, whereby effects of sequence variations in one part of the core promoter were reversed by variations in another part. In contrast, we observed robustness in Rap1 transcription factor binding sites, whereby significant sequence variations had little effect on promoter activity. Finally, cases in which orthologous promoter activities were not conserved could largely be explained by the sequence variation within the core promoter. Together, our results provide novel insights into the mechanisms by which expression is conserved throughout evolution across diverged promoter sequences.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors.forename: Danny
authors.initials: D
authors.lastname: Zeevi
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel;
authors.forename: Shai
authors.initials: S
authors.lastname: Lubliner
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Lotan-Pompan
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Hodis
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel;
authors.forename: Rita
authors.initials: R
authors.lastname: Vesterman
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors.forename: Adina
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel eran.segal@weizmann.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
mesh_terms: D001665:Binding Sites; D019143:Evolution, Molecular; D015966:Gene Expression Regulation, Fungal; D014644:Genetic Variation; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D012269:Ribosomal Proteins; D014157:Transcription Factors