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

Abstract Background 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 (GPC...

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Main Authors:	A. D. Lokits, H. Indrischek, J. Meiler, H. E. Hamm, P. F. Stadler
Format:	Article
Language:	English
Published:	BioMed Central 2018-04-01
Series:	BMC Evolutionary Biology
Subjects:	Heterotrimeric G protein G protein coupled receptors Evolution Whole genome duplication Paralog Orthology
Online Access:	http://link.springer.com/article/10.1186/s12862-018-1147-8

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spelling	doaj-art-4a36ba601249497cbd1dbcc4df4dd8ae2018-08-20T16:06:14ZengBioMed CentralBMC Evolutionary Biology1471-21482018-04-0118112710.1186/s12862-018-1147-8Tracing the evolution of the heterotrimeric G protein α subunit in MetazoaA. D. Lokits0H. Indrischek1J. Meiler2H. E. Hamm3P. F. Stadler4Neuroscience Program, Vanderbilt UniversityBioinformatics Group, Department of Computer Science, Leipzig UniversityCenter for Structural Biology, Vanderbilt UniversityPharmacology Department, Vanderbilt University Medical CenterBioinformatics Group, Department of Computer Science, Leipzig UniversityAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12862-018-1147-8Heterotrimeric G proteinG protein coupled receptorsEvolutionWhole genome duplicationParalogOrthology
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	A. D. Lokits H. Indrischek J. Meiler H. E. Hamm P. F. Stadler
spellingShingle	A. D. Lokits H. Indrischek J. Meiler H. E. Hamm P. F. Stadler Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa BMC Evolutionary Biology Heterotrimeric G protein G protein coupled receptors Evolution Whole genome duplication Paralog Orthology
author_facet	A. D. Lokits H. Indrischek J. Meiler H. E. Hamm P. F. Stadler
author_sort	A. D. Lokits
title	Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa
title_short	Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa
title_full	Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa
title_fullStr	Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa
title_full_unstemmed	Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa
title_sort	tracing the evolution of the heterotrimeric g protein α subunit in metazoa
publisher	BioMed Central
series	BMC Evolutionary Biology
issn	1471-2148
publishDate	2018-04-01
description	Abstract Background 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. Results 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. Conclusions 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.
topic	Heterotrimeric G protein G protein coupled receptors Evolution Whole genome duplication Paralog Orthology
url	http://link.springer.com/article/10.1186/s12862-018-1147-8
_version_	1612686910679941120

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

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