title: Molecular evolution of the Yap/Yorkie proto-oncogene and elucidation of its core transcriptional program.
abstract: Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of their myriad developmental functions. Here we analyze the molecular evolution of the proto-oncogene yes-associated protein (Yap)/Yorkie, a key effector of the Hippo signaling pathway that controls organ size in both Drosophila and mammals. Based on heterologous functional analysis of evolutionarily distant Yap/Yorkie orthologs, we demonstrate that a structurally distinct interaction interface between Yap/Yorkie and its partner TEAD/Scalloped became fixed in the eumetazoan common ancestor. We then combine transcriptional profiling of tissues expressing phylogenetically diverse forms of Yap/Yorkie with ChIP-seq validation to identify a common downstream gene expression program underlying the control of tissue growth in Drosophila. Intriguingly, a subset of the newly identified Yorkie target genes are also induced by Yap in mammalian tissues, thus revealing a conserved Yap-dependent gene expression signature likely to mediate organ size control throughout bilaterian animals. Combined, these experiments provide new mechanistic insights while revealing the ancient evolutionary history of Hippo signaling.
authors: Stowers Institute for Medical Research, Kansas City, MO.
authors: Aissam
authors: A
authors: Ikmi
authors: Stowers Institute for Medical Research, Kansas City, MO.
authors: Bjoern
authors: B
authors: Gaertner
authors: Stowers Institute for Medical Research, Kansas City, MO.
authors: Christopher
authors: C
authors: Seidel
authors: Whitehead Institute for Biomedical Research, Cambridge, MA.
authors: Mansi
authors: M
authors: Srivastava
authors: Stowers Institute for Medical Research, Kansas City, MODepartment of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, KS.
authors: Julia
authors: J
authors: Zeitlinger
authors: Stowers Institute for Medical Research, Kansas City, MODepartment of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS MG2@stowers.org.
authors: Matthew C
authors: MC
authors: Gibson
mesh_terms: D000818:Animals; D001483:Base Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D017423:Sequence Analysis, RNA; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D000090063:Proto-Oncogene Mas; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C000715470:MAS1 protein, human; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Metazoa; Yap; evolution; growth control; target genes