Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa

Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, Gα and a Gβγ dimer. The role of Gα as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their bi...

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Bibliographic Details
Published in:	BMC evolutionary biology Vol. 18; no. 1; pp. 51 - 27
Main Authors:	Lokits, A D, Indrischek, H, Meiler, J, Hamm, H E, Stadler, P F
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 11-04-2018 BioMed Central BMC
Subjects:	Animals DNA-Binding Proteins - genetics Evolution Evolution, Molecular G protein coupled receptors G proteins Gene Duplication Genetic aspects GTP-Binding Protein alpha Subunits - chemistry GTP-Binding Protein alpha Subunits - genetics GTP-Binding Protein alpha Subunits - metabolism Heterotrimeric G protein Metazoa Nucleotide Motifs Orthology Paralog Phylogeny Physiological aspects Properties Retroelements Signal Transduction Vertebrates - classification Vertebrates - genetics Whole genome duplication Heterotrimeric G protein Orthology G protein coupled receptors Paralog Evolution Genome annotation Whole genome duplication
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Summary:	Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, Gα and a Gβγ dimer. The role of Gα as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their biochemical and therapeutic importance, the study of G protein evolution has been limited to the scope of a few model organisms. Furthermore, of the five primary Gα subfamilies, the underlying gene structure of only two families has been thoroughly investigated outside of Mammalia evolution. Therefore our understanding of Gα emergence and evolution across phylogeny remains incomplete. We have computationally identified the presence and absence of every Gα gene (GNA-) across all major branches of Deuterostomia and evaluated the conservation of the underlying exon-intron structures across these phylogenetic groups. We provide evidence of mutually exclusive exon inclusion through alternative splicing in specific lineages. Variations of splice site conservation and isoforms were found for several paralogs which coincide with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our curated gene annotations, within Primates, we identified 15 retrotranspositions, many of which have undergone pseudogenization. Most importantly, we find numerous deviations from previous findings regarding the presence and absence of individual GNA- genes, nuanced differences in phyla-specific gene copy numbers, novel paralog duplications and subsequent intron gain and loss events. Our curated annotations allow us to draw more accurate inferences regarding the emergence of all Gα family members across Metazoa and to present a new, updated theory of Gα evolution. Leveraging this, our results are critical for gaining new insights into the co-evolution of the Gα subunit and its many protein binding partners, especially therapeutically relevant G protein - GPCR signaling pathways which radiated in Vertebrata evolution.
ISSN:	1471-2148 1471-2148
DOI:	10.1186/s12862-018-1147-8