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Tine, M.* ; Kuhl, H.* ; Teske, P.R.* ; Tschöp, M.H. ; Jastroch, M.

Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates.

Ecol. Evol. 6, 2516-2535 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The gut hormone ghrelin is involved in numerous metabolic functions, such as the stimulation of growth hormone secretion, gastric motility, and food intake. Ghrelin is modified by ghrelin O-acyltransferase (GOAT) or membrane-bound O-acyltransferase domain-containing 4 (MBOAT4) enabling action through the growth hormone secretagogue receptors (GHS-R). During the course of evolution, initially strong ligand/receptor specificities can be disrupted by genomic changes, potentially modifying physiological roles of the ligand/receptor system. Here, we investigated the coevolution of ghrelin, GOAT, and GHS-R in vertebrates. We combined similarity search, conserved synteny analyses, phylogenetic reconstructions, and protein structure comparisons to reconstruct the evolutionary history of the ghrelin system. Ghrelin remained a single-gene locus in all vertebrate species, and accordingly, a single GHS-R isoform was identified in all tetrapods. Similar patterns of the nonsynonymous (dN) and synonymous (dS) ratio (dN/dS) in the vertebrate lineage strongly suggest coevolution of the ghrelin and GHS-R genes, supporting specific functional interactions and common physiological pathways. The selection profiles do not allow confirmation as to whether ghrelin binds specifically to GOAT, but the ghrelin dN/dS patterns are more similar to those of GOAT compared to MBOAT1 and MBOAT2 isoforms. Four GHS-R isoforms were identified in teleost genomes. This diversification of GHS-R resulted from successive rounds of duplications, some of which remained specific to the teleost lineage. Coevolution signals are lost in teleosts, presumably due to the diversification of GHS-R but not the ghrelin gene. The identification of the GHS-R diversity in teleosts provides a molecular basis for comparative studies on ghrelin's physiological roles and regulation, while the comparative sequence and structure analyses will assist translational medicine to determine structure-function relationships of the ghrelin/GHS-R system.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Coevolution ; Divergence ; Function ; Ghrelin ; Growth Hormone Secretagogue Receptor ; Vertebrates; Growth-hormone; Solvent Accessibility; Genome Duplication; Protein Evolution; Functional-characterization; Nonsynonymous Substitution; Structural Determinants; Genes; Identification; Selection
e-ISSN 2045-7758
Zeitschrift Ecology and Evolution
Quellenangaben Band: 6, Heft: 8, Seiten: 2516-2535 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort [S.l.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)