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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 for Type I GnRH receptors, aligned using MUSCLE[32]. The Type I receptors identified in chimaeras and coelacanths (uppermost sequences) share high sequence similarity with those from mammals as well as identical intron-exon boundaries (arrowheads) and the lack of a cytoplasmic C-terminal domain. Amino acids that are highly conserved (>80% sequence identity) are indicated with the darkest shading; lighter shading indicates 60-80% identity; the lightest shading indicates 40-60% identity; and a white background indicates low conservation (<40% identity). Transmembrane domains were predicted using HMMTOP 2.0 [30] and are indicated with dark lines surrounding the relevant portion of the sequences. Latin names of species and accession numbers for sequences are provided in Additional file 1: Table S1.
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Fig6: Complete open reading frame sequences for Type I GnRH receptors, aligned using MUSCLE[32]. The Type I receptors identified in chimaeras and coelacanths (uppermost sequences) share high sequence similarity with those from mammals as well as identical intron-exon boundaries (arrowheads) and the lack of a cytoplasmic C-terminal domain. Amino acids that are highly conserved (>80% sequence identity) are indicated with the darkest shading; lighter shading indicates 60-80% identity; the lightest shading indicates 40-60% identity; and a white background indicates low conservation (<40% identity). Transmembrane domains were predicted using HMMTOP 2.0 [30] and are indicated with dark lines surrounding the relevant portion of the sequences. Latin names of species and accession numbers for sequences are provided in Additional file 1: Table S1.

Mentions: Although the Type I receptors had previously been known only from mammals, we found full length sequences of this receptor type in the genomes of a coelacanth (Latimeria chalumnae) and a chimaera (the elephant shark Callorhinchus milii), as well as partial sequence orthologs in the genome of the little skate (Leucoraja erinacea)(see Additional file 1: Table S1 and below). Like the Type I receptor in mammals, those in coelacanths and chimaera lack the cytoplasmic tail, terminating at the same amino acid. The putative Type I receptors also share the same intron-exon boundaries, strongly indicative of orthology. FigureĀ 6 illustrates the alignment of these sequences and the locations of exon boundaries.Figure 6


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 for Type I GnRH receptors, aligned using MUSCLE[32]. The Type I receptors identified in chimaeras and coelacanths (uppermost sequences) share high sequence similarity with those from mammals as well as identical intron-exon boundaries (arrowheads) and the lack of a cytoplasmic C-terminal domain. Amino acids that are highly conserved (>80% sequence identity) are indicated with the darkest shading; lighter shading indicates 60-80% identity; the lightest shading indicates 40-60% identity; and a white background indicates low conservation (<40% identity). Transmembrane domains were predicted using HMMTOP 2.0 [30] and are indicated with dark lines surrounding the relevant portion of the sequences. Latin names of species and accession numbers for sequences are provided in Additional file 1: Table S1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Complete open reading frame sequences for Type I GnRH receptors, aligned using MUSCLE[32]. The Type I receptors identified in chimaeras and coelacanths (uppermost sequences) share high sequence similarity with those from mammals as well as identical intron-exon boundaries (arrowheads) and the lack of a cytoplasmic C-terminal domain. Amino acids that are highly conserved (>80% sequence identity) are indicated with the darkest shading; lighter shading indicates 60-80% identity; the lightest shading indicates 40-60% identity; and a white background indicates low conservation (<40% identity). Transmembrane domains were predicted using HMMTOP 2.0 [30] and are indicated with dark lines surrounding the relevant portion of the sequences. Latin names of species and accession numbers for sequences are provided in Additional file 1: Table S1.
Mentions: Although the Type I receptors had previously been known only from mammals, we found full length sequences of this receptor type in the genomes of a coelacanth (Latimeria chalumnae) and a chimaera (the elephant shark Callorhinchus milii), as well as partial sequence orthologs in the genome of the little skate (Leucoraja erinacea)(see Additional file 1: Table S1 and below). Like the Type I receptor in mammals, those in coelacanths and chimaera lack the cytoplasmic tail, terminating at the same amino acid. The putative Type I receptors also share the same intron-exon boundaries, strongly indicative of orthology. FigureĀ 6 illustrates the alignment of these sequences and the locations of exon boundaries.Figure 6

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