title: Evolutionary hierarchy of vertebrate-like heterotrimeric G protein families.
abstract: Heterotrimeric G proteins perform a crucial role as molecular switches controlling various cellular responses mediated by G protein-coupled receptor (GPCR) signaling pathway. Recent data have shown that the vertebrate-like G protein families are found across metazoans and their closest unicellular relatives. However, an overall evolutionary hierarchy of vertebrate-like G proteins, including gene family annotations and in particular mapping individual gene gain/loss events across diverse holozoan lineages is still incomplete. Here, with more expanded invertebrate taxon sampling, we have reconstructed phylogenetic trees for each of the G protein classes/families and provide a robust classification and hierarchy of vertebrate-like heterotrimeric G proteins. Our results further extend the evidence that the common ancestor (CA) of holozoans had at least five ancestral Gα genes corresponding to all major vertebrate Gα classes and contain a total of eight genes including two Gβ and one Gγ. Our results also indicate that the GNAI/O-like gene likely duplicated in the last CA of metazoans to give rise to GNAI- and GNAO-like genes, which are conserved across invertebrates. Moreover, homologs of GNB1-4 paralogon- and GNB5 family-like genes are found in most metazoans and that the unicellular holozoans encode two ancestral Gβ genes. Similarly, most bilaterian invertebrates encode two Gγ genes which include a representative of the GNG gene cluster and a putative homolog of GNG13. Interestingly, our results also revealed key evolutionary events such as the Drosophila melanogaster eye specific Gβ subunit that is found conserved in most arthropods and several previously unidentified species specific expansions within Gαi/o, Gαs, Gαq, Gα12/13 classes and the GNB1-4 paralogon. Also, we provide an overall proposed evolutionary scenario on the expansions of all G protein families in vertebrate tetraploidizations. Our robust classification/hierarchy is essential to further understand the differential roles of GPCR/G protein mediated intracellular signaling system across various metazoan lineages.
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: arunkumar.krishnan@neuro.uu.se.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: arshi.mustafa@ebc.uu.se.
authors.forename: Arshi
authors.initials: A
authors.lastname: Mustafa
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: markus.almen@imbim.uu.se.
authors.forename: Markus Sällman
authors.initials: MS
authors.lastname: Almén
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: robert.fredriksson@neuro.uu.se.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: michael.williams@neuro.uu.se.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Electronic address: helgi.schioth@neuro.uu.se.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020962:Heterotrimeric GTP-Binding Proteins / Q000145:classification* / Q000235:genetics*; D007448:Invertebrates / Q000235:genetics; D005810:Multigene Family; D010802:Phylogeny; D014714:Vertebrates / Q000235:genetics
chemical_list: D020962:Heterotrimeric GTP-Binding Proteins
keywords: G protein; GPCRs; Gene gain/losses; Holozoans; Signal transduction