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Dynamic evolution of the GnRH receptor gene family in vertebrates.

Williams BL, Akazome Y, Oka Y, Eisthen HL - BMC Evol. Biol. (2014)

Bottom Line: Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors.We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss.Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy.

Results: We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses.

Conclusion: Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss. Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

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Related in: MedlinePlus

cDNA and deduced amino acid sequence of the GnRH receptor IIa-3 gene in axolotls. Analysis and formatting as described in Figure 1.
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Fig2: cDNA and deduced amino acid sequence of the GnRH receptor IIa-3 gene in axolotls. Analysis and formatting as described in Figure 1.

Mentions: Nucleotide and predicted amino acid sequences of the three receptors are illustrated in Figures 1, 2, and 3. Predicted locations of the seven membrane-spanning regions, as well as predicted sites of G-protein interaction and phosphorylation, are also shown. As illustrated in Figure 4, the sequences obtained from axolotls exhibit high sequence similarity with those from other amphibians. Three ‘subtypes’ of receptors are apparent (see also Figure 5), and we did not detect additional paralogs or splice variants. Based on the results described below, we determined that two of the receptors fall into the category that Roch et al. [14] named “Type IIa” and that the third receptor falls into their “Type IIb” category. We have therefore named the three axolotl GnRH receptors IIa-2, IIa-3, and IIb, with GenBank accession numbers KF499141, KF499142, and KF499143, respectively.Figure 1


Dynamic evolution of the GnRH receptor gene family in vertebrates.

Williams BL, Akazome Y, Oka Y, Eisthen HL - BMC Evol. Biol. (2014)

cDNA and deduced amino acid sequence of the GnRH receptor IIa-3 gene in axolotls. Analysis and formatting as described in Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232701&req=5

Fig2: cDNA and deduced amino acid sequence of the GnRH receptor IIa-3 gene in axolotls. Analysis and formatting as described in Figure 1.
Mentions: Nucleotide and predicted amino acid sequences of the three receptors are illustrated in Figures 1, 2, and 3. Predicted locations of the seven membrane-spanning regions, as well as predicted sites of G-protein interaction and phosphorylation, are also shown. As illustrated in Figure 4, the sequences obtained from axolotls exhibit high sequence similarity with those from other amphibians. Three ‘subtypes’ of receptors are apparent (see also Figure 5), and we did not detect additional paralogs or splice variants. Based on the results described below, we determined that two of the receptors fall into the category that Roch et al. [14] named “Type IIa” and that the third receptor falls into their “Type IIb” category. We have therefore named the three axolotl GnRH receptors IIa-2, IIa-3, and IIb, with GenBank accession numbers KF499141, KF499142, and KF499143, respectively.Figure 1

Bottom Line: Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors.We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss.Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy.

Results: We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses.

Conclusion: Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss. Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

Show MeSH
Related in: MedlinePlus