Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters
- Danny Zeevi1,2,3,4,
- Shai Lubliner1,4,
- Maya Lotan-Pompan1,2,
- Eran Hodis1,2,
- Rita Vesterman1,
- Adina Weinberger1,2 and
- Eran Segal1,2
- 1Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel;
- 2Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel
- Corresponding author: eran.segal{at}weizmann.ac.il
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↵4 These authors contributed equally to this work.
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.179259.114.
- Received June 2, 2014.
- Accepted October 6, 2014.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
