The fifth class of Gα proteins

Abstract

All ␣-subunits of vertebrate heterotrimeric G proteins have been classified into 4 major classes, Gs, Gi, Gq, and G12, which possess orthologs already in sponges, one of the earliest animal phyla to evolve. Here we report the discovery of the fifth class of G␣ protein, Gv, ancient like the other 4 classes, with members already in sponges, and encoded by 1-2 gnav genes per species. Gv is conserved across the animal kingdom including vertebrates, arthropods, mollusks, and annelids, but has been lost in many lineages such as nematodes, fruit fly, jawless fish, and tetrapods, concordant with a birth-and-death mode of evolution. All Gv proteins contain 5 G-box motifs characteristic of GTP-binding proteins and the expected acylation consensus sites in the Nterminal region. Sixty amino acid residues are conserved only among Gv, suggesting that they may constitute interaction sites for Gv-specific partner molecules. Overall Gv homology is high, on average 70% amino acid identity among vertebrate family members. The dN/dS analysis of teleost gnav genes reveals evolution under stringent negative selection. Genomic structure of vertebrate gnav genes is well conserved and different from those of the other 4 classes. The predicted full ORF of zebrafish gnav1 was confirmed by isolation from cDNA. RT-PCR analysis showed broad expression of gnav1 in adult zebrafish and in situ hybridization demonstrated a more restricted expression in larval tissues including the developing inner ear. The discovery of this fifth class of G␣ proteins changes our understanding of G protein evolution.Danio rerio ͉ evolution ͉ metazoan ͉ heterotrimeric G protein ͉ birth-and-death mode

Expansion of transducin subunit gene families in early vertebrate tetraploidizations

“…The superfamily encompassing the sixteen GNA genes can be subdivided into four different classes based on sequence similarities and functional specialisations: GNAI, GNAS, GNAQ and GNA12/13 [15,16]. An additional class has been identified in teleost fish as well as in invertebrates, GNAV, giving a total of five GNA gene classes [15].…”

Membrane-Localized Extra-Large G Proteins and Gβγ of the Heterotrimeric G Proteins Form Functional Complexes Engaged in Plant Immunity in Arabidopsis

“…Sequences representing the major plant phyla, five classes of Ga identified in animals (Suga et al, 1999;Oka et al, 2009), and two Ga proteins from the basal eukaryote Trichomonas vaginalis (Hirt et al, 2003) were selected (Supplemental Table S1). The T. vaginalis sequences were used as an outgroup.…”

“…The large diversity of mammalian Ga subunits confers specificity to the multiple signaling pathways mediated by G proteins (Wettschureck and Offermanns, 2005). Five distinct classes of Ga have been described in animals (Gai, Gaq, Gas, Ga12 and Gav), with orthologs found in evolutionarily primitive organisms such as sponges (Oka et al, 2009). Humans possess four classes of Ga involving 23 functional isoforms encoded by 16 genes (McCudden et al, 2005), while only a single prototypical Ga is usually found per plant genome (Urano et al, 2013).…”

Identification and Modulation of Voltage-Gated Ca2+Currents in Zebrafish Rohon-Beard Neurons

“…Finally, the diversity of G␣ subunits in zebrafish is actually greater than that of mammals. Recently a fifth class of G␣ protein, termed G v , was identified in zebrafish (Oka et al 2009). Although related to the G i family, this class of G proteins appears to be under stringent negative selection and is found in only a few organisms.…”