title: Intercalation of a new tier of transcription regulation into an ancient circuit.
abstract: Changes in gene regulatory networks are a major source of evolutionary novelty. Here we describe a specific type of network rewiring event, one that intercalates a new level of transcriptional control into an ancient circuit. We deduce that, over evolutionary time, the direct ancestral connections between a regulator and its target genes were broken and replaced by indirect connections, preserving the overall logic of the ancestral circuit but producing a new behaviour. The example was uncovered through a series of experiments in three ascomycete yeasts: the bakers' yeast Saccharomyces cerevisiae, the dairy yeast Kluyveromyces lactis and the human pathogen Candida albicans. All three species have three cell types: two mating-competent cell forms (a and α) and the product of their mating (a/α), which is mating-incompetent. In the ancestral mating circuit, two homeodomain proteins, Mata1 and Matα2, form a heterodimer that directly represses four genes that are expressed only in a and α cells and are required for mating. In a relatively recent ancestor of K. lactis, a reorganization occurred. The Mata1-Matα2 heterodimer represses the same four genes (known as the core haploid-specific genes) but now does so indirectly through an intermediate regulatory protein, Rme1. The overall logic of the ancestral circuit is preserved (haploid-specific genes ON in a and α cells and OFF in a/α cells), but a new phenotype was produced by the rewiring: unlike S. cerevisiae and C. albicans, K. lactis integrates nutritional signals, by means of Rme1, into the decision of whether or not to mate.
authors.affiliation: Department of Microbiology and Immunology and Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Booth
authors.forename: Brian B
authors.initials: BB
authors.lastname: Tuch
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007716:Kluyveromyces / Q000166:cytology / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; D018398:Homeodomain Proteins; C048632:MF(ALPHA)1 protein, S cerevisiae; D011498:Protein Precursors; C071594:RME1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins