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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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Complete open reading frame sequences of representative GnRH receptors, aligned using Clustal X[58]. Arrowheads indicate intron-exon boundaries. Locations of transmembrane domains (TM) are estimated based on those illustrated in [25] and in [10]. a = GnRH binding site for Type I receptors [59]; b = Gs coupling site in Type I receptors [24]; c = GnRH2 binds receptors containing D at this position, and does not bind receptors containing an N at this position [56]; d = GnRH binding site in both Type I and II receptors [24,55]; e = Gq/11 coupling site in Type I receptors [24]; f = GnRH binding site in Type II receptors [55]; g = sites contributing to differential sensitivity to GnRH1 and GnRH2 [57]; h = site involved in activation of the adenylyl cyclase/protein kinase A signaling pathway [60]; i = site involved in rapid internalization of Type II receptors [61].
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Fig10: Complete open reading frame sequences of representative GnRH receptors, aligned using Clustal X[58]. Arrowheads indicate intron-exon boundaries. Locations of transmembrane domains (TM) are estimated based on those illustrated in [25] and in [10]. a = GnRH binding site for Type I receptors [59]; b = Gs coupling site in Type I receptors [24]; c = GnRH2 binds receptors containing D at this position, and does not bind receptors containing an N at this position [56]; d = GnRH binding site in both Type I and II receptors [24,55]; e = Gq/11 coupling site in Type I receptors [24]; f = GnRH binding site in Type II receptors [55]; g = sites contributing to differential sensitivity to GnRH1 and GnRH2 [57]; h = site involved in activation of the adenylyl cyclase/protein kinase A signaling pathway [60]; i = site involved in rapid internalization of Type II receptors [61].

Mentions: ‡ Domain homology indicates the approximate physical position of the HMM with respect to the transmembrane (TM) domains in Figure 10.


Dynamic evolution of the GnRH receptor gene family in vertebrates.

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

Complete open reading frame sequences of representative GnRH receptors, aligned using Clustal X[58]. Arrowheads indicate intron-exon boundaries. Locations of transmembrane domains (TM) are estimated based on those illustrated in [25] and in [10]. a = GnRH binding site for Type I receptors [59]; b = Gs coupling site in Type I receptors [24]; c = GnRH2 binds receptors containing D at this position, and does not bind receptors containing an N at this position [56]; d = GnRH binding site in both Type I and II receptors [24,55]; e = Gq/11 coupling site in Type I receptors [24]; f = GnRH binding site in Type II receptors [55]; g = sites contributing to differential sensitivity to GnRH1 and GnRH2 [57]; h = site involved in activation of the adenylyl cyclase/protein kinase A signaling pathway [60]; i = site involved in rapid internalization of Type II receptors [61].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig10: Complete open reading frame sequences of representative GnRH receptors, aligned using Clustal X[58]. Arrowheads indicate intron-exon boundaries. Locations of transmembrane domains (TM) are estimated based on those illustrated in [25] and in [10]. a = GnRH binding site for Type I receptors [59]; b = Gs coupling site in Type I receptors [24]; c = GnRH2 binds receptors containing D at this position, and does not bind receptors containing an N at this position [56]; d = GnRH binding site in both Type I and II receptors [24,55]; e = Gq/11 coupling site in Type I receptors [24]; f = GnRH binding site in Type II receptors [55]; g = sites contributing to differential sensitivity to GnRH1 and GnRH2 [57]; h = site involved in activation of the adenylyl cyclase/protein kinase A signaling pathway [60]; i = site involved in rapid internalization of Type II receptors [61].
Mentions: ‡ Domain homology indicates the approximate physical position of the HMM with respect to the transmembrane (TM) domains in Figure 10.

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