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      Molecular Evolutionary Characterization of a V1R Subfamily Unique to Strepsirrhine Primates

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          Abstract

          Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1R strep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1R strep-α and V1R strep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1R strep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available.

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          Most cited references75

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          Crystal structure of rhodopsin: A G protein-coupled receptor.

          Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane alpha helices connected by six loops of varying lengths. We determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of key residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identification of a set of residues that mediate interactions between the transmembrane helices and the cytoplasmic surface, where G-protein activation occurs, also suggests a possible structural change upon photoactivation.
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            Codon-substitution models for heterogeneous selection pressure at amino acid sites.

            Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.
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              Statistical tests for detecting gene conversion.

              S. Sawyer (1989)
              Statistical tests for detecting gene conversion are described for a sample of homologous DNA sequences. The tests are based on imbalances in the distribution of segments on which some pair of sequences agrees. The methods automatically control for variable mutation rates along the genome and do not depend on a priori choices of potentially monophyletic subsets of the sample. The tests show strong evidence for multiple intragenic conversion events at two loci in Escherichia coli. The gnd locus in E. coli shows a highly significant excess of maximal segments of length 70-200 bp, which suggests conversion events of that size. The data also indicate that the rate of these short conversion events might be of the order of neutral mutation rate. There is also evidence for correlated mutation in adjacent codon positions. The same tests applied to a locus in an RNA virus were negative.
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                Author and article information

                Journal
                Genome Biol Evol
                Genome Biol Evol
                gbe
                gbe
                Genome Biology and Evolution
                Oxford University Press
                1759-6653
                2014
                6 January 2014
                January 2014
                6 January 2014
                : 6
                : 1
                : 213-227
                Affiliations
                1Department of Biology, Duke University
                2Department of Genetics, Evolution and Environment, University College London, London, United Kingdom
                3Département de Biologie Animale, Université d’Antananarivo, Antananarivo, Madagascar
                4Gene Bank of Primates and Primate Genetics Laboratory, German Primate Center (DPZ), Göttingen, Germany
                5UCSF Center for Health & Community
                6Behavioral Ecology and Sociobiology Unit, German Primate Center (DPZ), Göttingen, Germany
                7Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada
                Author notes
                *Corresponding author: E-mail: anne.yoder@ 123456duke.edu .

                Associate editor: George Zhang

                Data deposition: The sequence data from this study have been deposited at GenBank under the accession KF271799–KF272802.

                These authors contributed equally to this work.

                Article
                evu006
                10.1093/gbe/evu006
                3914689
                24398377
                07ad8e68-3921-4d5c-ab1e-680fbee9328f
                © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 December 2013
                Page count
                Pages: 15
                Categories
                Research Article

                Genetics
                chemosensory genes,positive selection,lemurs,olfaction,gene family evolution,g-protein-coupled receptors

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