title: Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network.
abstract: The emergence of new genes throughout evolution requires rewiring and extension of regulatory networks. However, the molecular details of how the transcriptional regulation of new gene copies evolves remain largely unexplored. Here we show how duplication of a transcription factor gene allowed the emergence of two independent regulatory circuits. Interestingly, the ancestral transcription factor was promiscuous and could bind different motifs in its target promoters. After duplication, one paralogue evolved increased binding specificity so that it only binds one type of motif, whereas the other copy evolved a decreased activity so that it only activates promoters that contain multiple binding sites. Interestingly, only a few mutations in both the DNA-binding domains and in the promoter binding sites were required to gradually disentangle the two networks. These results reveal how duplication of a promiscuous transcription factor followed by concerted cis and trans mutations allows expansion of a regulatory network.
authors.affiliation: 1] Laboratory for Genetics and Genomics, Department M2S, Centre of Microbial and Plant Genetics (CMPG), KU Leuven, B-3001 Leuven, Belgium [2] Laboratory for Systems biology, Vlaams Instituut voor Biotechnologie (VIB), B-3001 Leuven, Belgium.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Pougach
authors.affiliation: Structural Bioinformatics, Center for Life Science Technologies (CLST), RIKEN, 230-0045 Yokohama, Japan.
authors.forename: Arnout
authors.initials: A
authors.lastname: Voet
authors.affiliation: Laboratory of Evolutionary Genomics, Centre for genomic regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Fyodor A
authors.initials: FA
authors.lastname: Kondrashov
authors.affiliation: 1] Laboratory for Genetics and Genomics, Department M2S, Centre of Microbial and Plant Genetics (CMPG), KU Leuven, B-3001 Leuven, Belgium [2] Laboratory for Systems biology, Vlaams Instituut voor Biotechnologie (VIB), B-3001 Leuven, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Voordeckers
authors.affiliation: 1] Laboratory for Genetics and Genomics, Department M2S, Centre of Microbial and Plant Genetics (CMPG), KU Leuven, B-3001 Leuven, Belgium [2] Laboratory for Systems biology, Vlaams Instituut voor Biotechnologie (VIB), B-3001 Leuven, Belgium.
authors.forename: Joaquin F
authors.initials: JF
authors.lastname: Christiaens
authors.affiliation: Genomics Core Facility, European Molecular Biology Laboratory Heidelberg (EMBL), 69117 Heidelberg, Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Baying
authors.affiliation: Genomics Core Facility, European Molecular Biology Laboratory Heidelberg (EMBL), 69117 Heidelberg, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: 1] Department of Electrical Engineering, STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, B-3001 Leuven, Belgium [2] iMinds Medical Information Technologies Department, KU Leuven, B-3001 Leuven, Belgium.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sakai
authors.affiliation: 1] Department of Electrical Engineering, STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, B-3001 Leuven, Belgium [2] iMinds Medical Information Technologies Department, KU Leuven, B-3001 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Aerts
authors.affiliation: 1] Laboratory for Genetics and Genomics, Department M2S, Centre of Microbial and Plant Genetics (CMPG), KU Leuven, B-3001 Leuven, Belgium [2] Laboratory for Systems biology, Vlaams Instituut voor Biotechnologie (VIB), B-3001 Leuven, Belgium.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: 1] Molecular Microbiology and Biotechnology Section, KU Leuven, B-3001 Leuven, Belgium [2] Department of Molecular Microbiology, VIB, B-3001 Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dijck
authors.affiliation: 1] Laboratory for Genetics and Genomics, Department M2S, Centre of Microbial and Plant Genetics (CMPG), KU Leuven, B-3001 Leuven, Belgium [2] Laboratory for Systems biology, Vlaams Instituut voor Biotechnologie (VIB), B-3001 Leuven, Belgium.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Verstrepen
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D005959:Glucosidases / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D009004:Monosaccharide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005959:Glucosidases; D000520:alpha-Glucosidases