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The Origin of GPCRs: Identification of Mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in Fungi
Open accessAbstract
G protein-coupled receptors (GPCRs) in humans are classified into the five main families named Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin according to the GRAFS classification. Previous results show that these mammalian GRAFS families are well represented in the Metazoan lineages, but they have not been shown to be present in Fungi. Here, we systematically mined 79 fungal genomes and provide the first evidence that four of the five main mammalian families of GPCRs, namely Rhodopsin, Adhesion, Glutamate and Frizzled, are present in Fungi and found 142 novel sequences between them. Significantly, we provide strong evidence that the Rhodopsin family emerged from the cAMP receptor family in an event close to the split of Opisthokonts and not in Placozoa, as earlier assumed. The Rhodopsin family then expanded greatly in Metazoans while the cAMP receptor family is found in 3 invertebrate species and lost in the vertebrates. We estimate that the Adhesion and Frizzled families evolved before the split of Unikonts from a common ancestor of all major eukaryotic lineages. Also, the study highlights that the fungal Adhesion receptors do not have N-terminal domains whereas the fungal Glutamate receptors have a broad repertoire of mammalian-like N-terminal domains. Further, mining of the close unicellular relatives of the Metazoan lineage, Salpingoeca rosetta and Capsaspora owczarzaki, obtained a rich group of both the Adhesion and Glutamate families, which in particular provided insight to the early emergence of the N-terminal domains of the Adhesion family. We identified 619 Fungi specific GPCRs across 79 genomes and revealed that Blastocladiomycota and Chytridiomycota phylum have Metazoan-like GPCRs rather than the GPCRs specific for Fungi. Overall, this study provides the first evidence of the presence of four of the five main GRAFS families in Fungi and clarifies the early evolutionary history of the GPCR superfamily.
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Metadata
- Authors
- Krishnan, A., Almén, M. S., Fredriksson, R., & Schiöth, H. B.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Schiöth, Helgi B.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-01-04
- Volume
- 7
- Issue
- 1
- Pages
- e29817
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3251606
- OpenAlex
- W1983820999
- Cited by
- 204
- References
- 47
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 16 · 2023: 11 · 2022: 11 · 2021: 7 · 2020: 16 · 2019: 14 · 2018: 8 · 2017: 14 · 2016: 23 · 2015: 20 · 2014: 18 · 2013: 18 · 2012: 10
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Novo Nordisk
- Vetenskapsrådet
- Magnus Bergvalls Stiftelse
- Uppsala Universitet
- Novo Nordisk Fonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- G protein-coupled receptors, GPCR evolution, rhodopsin family, cell adhesion receptors, glutamate receptors, Frizzled receptors, N-terminal domain, Salpingoeca rosetta, Capsaspora owczarzaki, Blastocladiomycota, Chytridiomycota, fungal genome
- MeSH terms
- Amino Acid Sequence, Animals, Cloning, Molecular, Fungi, Genes, Fungal, Humans, Mammals, Molecular Sequence Data, Phylogeny, Rhodopsin, Cell Adhesion Molecules, Genome, Fungal, Receptors, Glutamate, Evolution, Molecular, Receptors, G-Protein-Coupled, Frizzled Receptors
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