Cited by 166Hippo pathway signaling and YAP/TAZDevelopmental Biology and Gene RegulationMarine Invertebrate Physiology and Ecology

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The Evolutionary History of YAP and the Hippo/YAP Pathway

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Hilman, D., Gat, U.·2011·Molecular Biology and Evolution

DOI 10.1093/molbev/msr065

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Abstract

The Hippo/YAP pathway plays an important role in animal organ size control, which it exerts by regulating tissue proliferation and apoptosis rates as a response to developmental cues, cell contact, and density. With the ever increasing advance in genome sequencing and analysis tools, our understanding of the animal world and its evolution has greatly increased in the recent years. We used bioinformatic tools to study the evolution of the Hippo/YAP pathway focusing on the transcriptional coactivator YAP, which is a pivotal effector of the pathway. The aim was to establish the origin and mode of development of YAP and its pathway in the animal world. Some pathway members can be already identified in single-celled eukaryotes like the yeast that have preceded multicellular animals. Interestingly, we can find most of the components that are present in human in the sea-anemone Nematostella, which belongs to a very basal group of metazoans, the cnidarians. All the major domains of YAP have been conserved between cnidarians and mammals, and YAP can be identified even in the more basal placozoan clade. We show a very high degree of conservation in regions such as the WW and the TEAD-binding domains, TEAD being the major DNA-binding partner of YAP. Remarkably, we found that the location of an intron in the WW1 genomic region has been invariant along an evolutionary span of over 700 My. We have followed the evolutionary changes in YAP and in other main components of the pathway from the first metazoans such as sponges, described the phylogenetic relationships between the YAP genes and indicated where YAP and other components have been secondarily lost. Evidence is provided that YAP and its binding partner TEAD demonstrate strong coevolution. This gives further support for the importance of the TEAD-YAP association. Beyond contributing to an understanding of the evolutionary history of this pathway, we have provided insights into the "birth" of this pathway, its functions and its mode of operation in animals with different body plans, development, and life styles.

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Authors: Hilman, D., & Gat, U.
Affiliations: Hebrew University of Jerusalem (IL)
Corresponding author: Gat, U.
Venue: Molecular Biology and Evolution
Publisher: Oxford University Press (OUP)
Published: 2011-03-16
Volume: 28
Issue: 8
Pages: 2403-2417
ISSN: 0737-4038 (ISSN-L)
1537-1719
DOI: 10.1093/molbev/msr065
OpenAlex: W2131418202
Cited by: 166
References: 88
Citations by year: 2026: 7 · 2025: 9 · 2024: 7 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 14 · 2019: 13 · 2018: 12 · 2017: 10 · 2016: 7 · 2015: 6 · 2014: 17 · 2013: 9 · 2012: 8
FWCI: 5.37
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Molecular Biology and Evolution (publishedVersion)
PubMed (publishedVersion)
Funders: Hebrew University of Jerusalem
Israel Science Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Marine Invertebrate Physiology and Ecology
Keywords: YAP, Hippo signaling pathway, TEAD, organ size control, tissue proliferation, apoptosis, evolution of signaling pathways, Nematostella, Cnidaria, placozoans, sponges, WW domain, intron conservation, gene loss, coevolution, phylogenetic relationships, multicellular animals
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Humans, Introns, Molecular Sequence Data, Phylogeny, Protein Binding, Transcription Factors, Molecular Structure, Signal Transduction, Sequence Alignment, Evolution, Molecular, Amino Acid Motifs, Gene Order, Intracellular Signaling Peptides and Proteins

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The Evolutionary History of YAP and the Hippo/YAP Pathway

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