Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits
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{"title"=>"Early evolution of ionotropic GABA receptors and selective regimes acting on the mammalian-specific theta and epsilon subunits", "type"=>"journal", "authors"=>[{"first_name"=>"Christopher J.", "last_name"=>"Martyniuk", "scopus_author_id"=>"6507932776"}, {"first_name"=>"Stéphane", "last_name"=>"Aris-Brosou", "scopus_author_id"=>"14046700900"}, {"first_name"=>"Guy", "last_name"=>"Drouin", "scopus_author_id"=>"7006217509"}, {"first_name"=>"Joel", "last_name"=>"Cahn", "scopus_author_id"=>"23983989000"}, {"first_name"=>"Vance L.", "last_name"=>"Trudeau", "scopus_author_id"=>"7006634572"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"351425882", "pmid"=>"17878929", "isbn"=>"10.1371/journal.pone.0000894", "doi"=>"10.1371/journal.pone.0000894", "sgr"=>"41149177407", "scopus"=>"2-s2.0-41149177407"}, "id"=>"34a21425-6686-3732-b9d9-a9dc3f9b78c3", "abstract"=>"BACKGROUND: The amino acid neurotransmitter GABA is abundant in the central nervous system (CNS) of both invertebrates and vertebrates. Receptors of this neurotransmitter play a key role in important processes such as learning and memory. Yet, little is known about the mode and tempo of evolution of the receptors of this neurotransmitter. Here, we investigate the phylogenetic relationships of GABA receptor subunits across the chordates and detail their mode of evolution among mammals.\\n\\nPRINCIPAL FINDINGS: Our analyses support two major monophyletic clades: one clade containing GABA(A) receptor alpha, gamma, and epsilon subunits, and another one containing GABA(A) receptor rho, beta, delta, theta, and pi subunits. The presence of GABA receptor subunits from each of the major clades in the Ciona intestinalis genome suggests that these ancestral duplication events occurred before the divergence of urochordates. However, while gene divergence proceeded at similar rates on most receptor subunits, we show that the mammalian-specific subunits theta and epsilon experienced an episode of positive selection and of relaxed constraints, respectively, after the duplication event. Sites putatively under positive selection are placed on a three-dimensional model obtained by homology-modeling.\\n\\nCONCLUSIONS: Our results suggest an early divergence of the GABA receptor subunits, before the split from urochordates. We show that functional changes occurred in the lineages leading to the mammalian-specific subunit theta, and we identify the amino acid sites putatively responsible for the functional divergence. We discuss potential consequences for the evolution of mammals and of their CNS.", "link"=>"http://www.mendeley.com/research/early-evolution-ionotropic-gaba-receptors-selective-regimes-acting-mammalianspecific-theta-epsilon-s", "reader_count"=>35, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>2, "Other"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>2, "Other"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>3, "Neuroscience"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Chemistry"=>2, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Argentina"=>1, "Egypt"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/945023"], "description"=>"<p>(a) the GABA<sub>A</sub> receptor θ and β subunits ; (b) the GABA<sub>A</sub> receptor ε and γ subunits. Selective pressures are allowed to vary among sets of branches to test for the a priori hypotheses listed at the bottom of the figure: H<sub>0</sub>: the null hypothesis that all branch-specific rates are equal; H<sub>1</sub>: burst of evolution following the main gene duplication event (ε/γ and θ/β); H<sub>2</sub>: also allows for a rate change after the burst of evolution; H<sub>3</sub>: extends H<sub>2</sub> to allow for burst of evolution after all duplication events depicted on each tree. Hypotheses test are reported in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000894#pone-0000894-t001\" target=\"_blank\">Tables 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000894#pone-0000894-t002\" target=\"_blank\">2</a>. The scale bar represents 0.1 substitutions per codon site, with branch lengths estimated under the null model (H<sub>0</sub>).</p>", "links"=>[], "tags"=>["trees", "formulate", "hypotheses", "selective", "forces", "shaped"], "article_id"=>615396, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_trees_used_to_formulate_hypotheses_about_the_selective_forces_that_shaped_the_evolution_of_the_GABA_A_subunits_/615396", "title"=>"Phylogenetic trees used to formulate hypotheses about the selective forces that shaped the evolution of the GABA<sub>A</sub> subunits.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-09-19 01:29:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/945157"], "description"=>"<p>Notes–<i>ℓ</i>: log-likelihood value; H<sub>A</sub>: alternative hypothesis to the current model; <i>ω</i><sub>0</sub>: background rate; <i>ω</i><sub>1–5</sub>: branch/clade specific rates as indicated in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000894#pone-0000894-g004\" target=\"_blank\">Figure 4</a>; <i>p</i><sub>0–2</sub>: proportions of sites in each rate category. The hat notation indicates parameters that are free to vary. Positively selected sites were identified with BEB and NEB between brackets for model A and NEB only for model B; a 99% cut-off level of posterior probability was used. Sites putatively under positive selection are numbered according to the human θ reference sequence (accession number BC109210/AAI09211). The underlined sites are those common to both model A and model B. Curly braces indicate equally parsimonious ancestral sites.</p>", "links"=>[], "tags"=>["comparisons", "parameter", "estimates", "ratios", "branches", "clades", "sites"], "article_id"=>615530, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_comparisons_and_parameter_estimates_under_models_of_constant_H_0_or_variable_969_rate_ratios_across_branches_Br_clades_H_1_to_H_3_or_both_clades_and_sites_A_and_B_for_the_952_subunit_/615530", "title"=>"Model comparisons and parameter estimates under models of constant (H<sub>0</sub>) or variable <i>ω</i> rate ratios across branches (Br), clades (H<sub>1</sub> to H<sub>3</sub>) or both clades and sites (A and B) for the θ subunit.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-09-19 01:32:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/944872"], "description"=>"<p>Bootstrap values are indicated at the nodes and the scale bar represents 1 amino acid substitutions per site.</p>", "links"=>[], "tags"=>["vertebrate", "gaba", "receptor", "sequences", "benzodiazepine", "binding"], "article_id"=>615246, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.g003", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogeny_of_vertebrate_GABA_receptor_protein_sequences_without_benzodiazepine_binding_sites_/615246", "title"=>"Phylogeny of vertebrate GABA receptor protein sequences without benzodiazepine binding sites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-09-19 01:27:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/945095"], "description"=>"<p>Sites putatively detected to be under positive selection on subunit θ under: (a) model A and (b) model B.</p>", "links"=>[], "tags"=>["sites", "putatively", "three-dimensional", "subunit"], "article_id"=>615472, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.g005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_of_the_sites_putatively_under_positive_selection_on_the_three_dimensional_models_of_the_subunit_of_the_GABA_A_receptor_/615472", "title"=>"Mapping of the sites putatively under positive selection on the three-dimensional models of the θ subunit of the GABA<sub>A</sub> receptor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-09-19 01:31:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/945201"], "description"=>"<p>Notes–<i>ℓ</i>: log-likelihood value; H<sub>A</sub>: alternative hypothesis to the current model; <i>ω</i><sub>0</sub>: background rate; <i>ω</i><sub>1–5</sub>: branch/clade specific rates as indicated in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000894#pone-0000894-g004\" target=\"_blank\">Figure 4</a>; <i>p</i><sub>0–2</sub>: proportions of sites in each rate category. The hat notation indicates parameters that are free to vary. Positively selected sites were identified with BEB and NEB between brackets for model A and NEB only for model B; a 95% cut-off level of posterior probability was used. Sites putatively under positive selection are numbered according to the human ε reference sequence (accession numbers HSU66661/AAB49284). †: these sites were putatively identified with a posterior probability >50% (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000894#pone.0000894.s001\" target=\"_blank\">text</a>). The underlined sites are those common to both model A and model B. Curly braces indicate equally parsimonious ancestral sites.</p>", "links"=>[], "tags"=>["comparisons", "parameter", "estimates", "ratios", "branches", "clades", "sites"], "article_id"=>615569, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_comparisons_and_parameter_estimates_under_models_of_constant_H_0_or_variable_969_rate_ratios_across_branches_Br_clades_H_1_to_H_3_or_both_clades_and_sites_A_and_B_for_the_949_subunit_/615569", "title"=>"Model comparisons and parameter estimates under models of constant (H<sub>0</sub>) or variable <i>ω</i> rate ratios across branches (Br), clades (H<sub>1</sub> to H<sub>3</sub>) or both clades and sites (A and B) for the ε subunit.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-09-19 01:32:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/944710"], "description"=>"<p>The two clades, based on the presence (α, γ, and ε) or absence (ρ, β, δ, θ, and π) of a benzodiazepine binding site, are indicated by BZ+ and BZ–, respectively. Bootstrap values (maximum likelihood analysis) are indicated at all nodes while posterior probabilities (Bayesian analysis) are only indicated when smaller than 100%. The scale bar represents 1 amino acid substitutions per site. Ach: acetylcholine receptor.</p>", "links"=>[], "tags"=>["gaba", "receptor"], "article_id"=>615092, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogeny_of_GABA_receptor_protein_sequences_/615092", "title"=>"Phylogeny of GABA receptor protein sequences.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-09-19 01:24:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/944788"], "description"=>"<p>Bootstrap values are indicated at the nodes and the scale bar represents 1 amino acid substitutions per site.</p>", "links"=>[], "tags"=>["vertebrate", "gaba", "receptor", "sequences", "benzodiazepine", "binding"], "article_id"=>615165, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000894.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogeny_of_vertebrate_GABA_receptor_protein_sequences_with_benzodiazepine_binding_sites_/615165", "title"=>"Phylogeny of vertebrate GABA receptor protein sequences with benzodiazepine binding sites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-09-19 01:26:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/465351", "https://ndownloader.figshare.com/files/465373"], "description"=>"<div><h3>Background</h3><p>The amino acid neurotransmitter GABA is abundant in the central nervous system (CNS) of both invertebrates and vertebrates. Receptors of this neurotransmitter play a key role in important processes such as learning and memory. Yet, little is known about the mode and tempo of evolution of the receptors of this neurotransmitter. Here, we investigate the phylogenetic relationships of GABA receptor subunits across the chordates and detail their mode of evolution among mammals.</p><h3>Principal Findings</h3><p>Our analyses support two major monophyletic clades: one clade containing GABA<sub>A</sub> receptor α, γ, and ε subunits, and another one containing GABA<sub>A</sub> receptor ρ, β, δ, θ, and π subunits. The presence of GABA receptor subunits from each of the major clades in the <em>Ciona intestinalis</em> genome suggests that these ancestral duplication events occurred before the divergence of urochordates. However, while gene divergence proceeded at similar rates on most receptor subunits, we show that the mammalian-specific subunits θ and ε experienced an episode of positive selection and of relaxed constraints, respectively, after the duplication event. Sites putatively under positive selection are placed on a three-dimensional model obtained by homology-modeling.</p><h3>Conclusions</h3><p>Our results suggest an early divergence of the GABA receptor subunits, before the split from urochordates. We show that functional changes occurred in the lineages leading to the mammalian-specific subunit θ, and we identify the amino acid sites putatively responsible for the functional divergence. We discuss potential consequences for the evolution of mammals and of their CNS.</p></div>", "links"=>[], "tags"=>["ionotropic", "gaba", "receptors", "selective", "regimes", "acting", "mammalian-specific", "theta", "epsilon", "subunits"], "article_id"=>151742, "categories"=>["Physiology", "Evolutionary Biology"], "users"=>["Christopher J. Martyniuk", "Stéphane Aris-Brosou", "Guy Drouin", "Joel Cahn", "Vance L. Trudeau"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0000894.s001", "https://dx.doi.org/10.1371/journal.pone.0000894.s002"], "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Early_Evolution_of_Ionotropic_GABA_Receptors_and_Selective_Regimes_Acting_on_the_Mammalian_Specific_Theta_and_Epsilon_Subunits/151742", "title"=>"Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-09-19 00:29:02"}

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Relative Metric

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