the evolution of combinatorial gene regulation in fungi在真菌的进化组合基因调控.pdfVIP

PLoS BIOLOGY The Evolution of Combinatorial Gene Regulation in Fungi 1,2[ 1,2[ 1,2 1* 1,2* Brian B. Tuch , David J. Galgoczy , Aaron D. Hernday , Hao Li , Alexander D. Johnson 1 Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America, 2 Department of Microbiology and Immunology, University of California, San Francisco, California, United States of America It is widely suspected that gene regulatory networks are highly plastic. The rapid turnover of transcription factor binding sites has been predicted on theoretical grounds and has been experimentally demonstrated in closely related species. We combined experimental approaches with comparative genomics to focus on the role of combinatorial control in the evolution of a large transcriptional circuit in the fungal lineage. Our study centers on Mcm1, a transcriptional regulator that, in combination with five cofactors, binds roughly 4% of the genes in Saccharomyces cerevisiae and regulates processes ranging from the cell-cycle to mating. In Kluyveromyces lactis and Candida albicans, two other hemiascomycetes, we find that the Mcm1 combinatorial circuits are substantially different. This massive rewiring of the Mcm1 circuitry has involved both substantial gain and loss of targets in ancient combinatorial circuits as well as the formation of new combinatorial interactions. We have dissected the gains and losses on the global level into subsets of functionally and temporally related changes. One particularly dramatic change is the acquisition of Mcm1 bi