RT Journal
A1 Zeevi, Danny
A1 Lubliner, Shai
A1 Lotan-Pompan, Maya
A1 Hodis, Eran
A1 Vesterman, Rita
A1 Weinberger, Adina
A1 Segal, Eran
T1 Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters
JF Genome Research 
JO Genome Research 
YR 2014 
FD December 01 
VO 24 
IS 12 
SP 1991 
OP 1999 
DO 10.1101/gr.179259.114 
UL http://genome.cshlp.org/content/24/12/1991.abstract 
AB 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.