Ilan Wapinski a,b,1, Jenna Pfiffner b, Courtney French b, Amanda Socha b, Dawn Anne Thompson b, and
Aviv Regev b,c,1
-Author Affiliations
aDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115;
bBroad Institute of MIT and Harvard and
cHoward Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142
Edited* by Eric S. Lander, Broad Institute of MIT and Harvard, Cambridge, MA, and approved February 1, 2010 (received for review October 15, 2009)
Abstract
Coexpression of genes within a functional module can be conserved at great evolutionary distances, whereas the associated regulatory mechanisms can substantially diverge. For example, ribosomal protein (RP) genes are tightly coexpressed in Saccharomyces cerevisiae, but the cis and trans factors associated with them are surprisingly diverged across Ascomycota fungi. Little is known, however, about the functional impact of such changes on actual expression levels or about the selective pressures that affect them. Here, we address this question in the context of the evolution of the regulation of RP gene expression by using a comparative genomics approach together with cross-species functional assays. We show that an activator (Ifh1) and a repressor (Crf1) that control RP gene regulation in normal and stress conditions in S. cerevisiae are derived from the duplication and subsequent specialization of a single ancestral protein. We provide evidence that this regulatory innovation coincides with the duplication of RP genes in a whole-genome duplication (WGD) event and may have been important for tighter control of higher levels of RP transcripts. We find that subsequent loss of the derived repressor led to the loss of a stress-dependent repression of RPs in the fungal pathogen Candida glabrata. Our comparative computational and experimental approach shows how gene duplication can constrain and drive regulatory evolution and provides a general strategy for reconstructing the evolutionary trajectory of gene regulation across species.
stress response comparative functional genomics regulatory modules expression profiling
Footnotes
1To whom correspondence may be addressed. E-mail:ilan_wapinski@hms.harvard.edu or aregev@broad.mit.edu.
Author contributions: I.W., D.A.T., and A.R. designed research; I.W., J.P., C.F., A.S., and D.A.T. performed research; I.W. and A.R. analyzed data; and I.W. and A.R. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
Data deposition: Gene expression data is available at http://www.broadinstitute.org/~ilan/PNAS2010
This article contains supporting information online at www.pnas.org/cgi/content/full/0911905107/DCSupplemental.
Freely available online through the PNAS open access option.
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