Coevolution within a transcriptional network by compensatory trans and cis mutations.
Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of "coevolution" between a DNA-binding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.
Kuo
Dwight
D
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
Licon
Katherine
K
Bandyopadhyay
Sourav
S
Chuang
Ryan
R
Luo
Colin
C
Catalana
Justin
J
Ravasi
Timothy
T
Tan
Kai
K
Ideker
Trey
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D041221:Candida glabrata / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks / Q000235:genetics*; D046228:Microarray Analysis / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
D018808:Transcription Factor AP-1