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Citation
Ikmi, A., Gaertner, B., Seidel, C., Srivastava, M., Zeitlinger, J., Gibson, M.C. (2014). Molecular evolution of the yap/yorkie proto-oncogene and elucidation of its core transcriptional program.  Mol. Biol. Evol. 31(6): 1375--1390.
FlyBase ID
FBrf0225127
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC4032125 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Biol. Evol.
    Title
    Molecular Biology and Evolution
    Publication Year
    1983-
    ISBN/ISSN
    0737-4038 1537-1719
    Data From Reference