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      Adaptive Evolution in the Glucose Transporter 4 Gene Slc2a4 in Old World Fruit Bats (Family: Pteropodidae)

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          Abstract

          Frugivorous and nectarivorous bats are able to ingest large quantities of sugar in a short time span while avoiding the potentially adverse side-effects of elevated blood glucose. The glucose transporter 4 protein (GLUT4) encoded by the Slc2a4 gene plays a critical role in transmembrane skeletal muscle glucose uptake and thus glucose homeostasis. To test whether the Slc2a4 gene has undergone adaptive evolution in bats with carbohydrate-rich diets in relation to their insect-eating sister taxa, we sequenced the coding region of the Slc2a4 gene in a number of bat species, including four Old World fruit bats (Pteropodidae) and three New World fruit bats (Phyllostomidae). Our molecular evolutionary analyses revealed evidence that Slc2a4 has undergone a change in selection pressure in Old World fruit bats with 11 amino acid substitutions detected on the ancestral branch, whereas, no positive selection was detected in the New World fruit bats. We noted that in the former group, amino acid replacements were biased towards either Serine or Isoleucine, and, of the 11 changes, six were specific to Old World fruit bats (A133S, A164S, V377F, V386I, V441I and G459S). Our study presents preliminary evidence that the Slc2a4 gene has undergone adaptive changes in Old World fruit bats in relation to their ability to meet the demands of a high sugar diet.

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          Most cited references35

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          Statistical methods for detecting molecular adaptation.

          The past few years have seen the development of powerful statistical methods for detecting adaptive molecular evolution. These methods compare synonymous and nonsynonymous substitution rates in protein-coding genes, and regard a nonsynonymous rate elevated above the synonymous rate as evidence for darwinian selection. Numerous cases of molecular adaptation are being identified in various systems from viruses to humans. Although previous analyses averaging rates over sites and time have little power, recent methods designed to detect positive selection at individual sites and lineages have been successful. Here, we summarize recent statistical methods for detecting molecular adaptation, and discuss their limitations and possible improvements.
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            Resolution of the early placental mammal radiation using Bayesian phylogenetics.

            Molecular phylogenetic studies have resolved placental mammals into four major groups, but have not established the full hierarchy of interordinal relationships, including the position of the root. The latter is critical for understanding the early biogeographic history of placentals. We investigated placental phylogeny using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set. Interordinal relationships are almost entirely resolved. The basal split is between Afrotheria and other placentals, at about 103 million years, and may be accounted for by the separation of South America and Africa in the Cretaceous. Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana).
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              Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver.

              The earliest defect in developing type 2 diabetes is insulin resistance, characterized by decreased glucose transport and metabolism in muscle and adipocytes. The glucose transporter GLUT4 mediates insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane. In insulin-resistant states such as obesity and type 2 diabetes, GLUT4 expression is decreased in adipose tissue but preserved in muscle. Because skeletal muscle is the main site of insulin-stimulated glucose uptake, the role of adipose tissue GLUT4 downregulation in the pathogenesis of insulin resistance and diabetes is unclear. To determine the role of adipose GLUT4 in glucose homeostasis, we used Cre/loxP DNA recombination to generate mice with adipose-selective reduction of GLUT4 (G4A-/-). Here we show that these mice have normal growth and adipose mass despite markedly impaired insulin-stimulated glucose uptake in adipocytes. Although GLUT4 expression is preserved in muscle, these mice develop insulin resistance in muscle and liver, manifested by decreased biological responses and impaired activation of phosphoinositide-3-OH kinase. G4A-/- mice develop glucose intolerance and hyperinsulinaemia. Thus, downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                6 April 2012
                : 7
                : 4
                : e33197
                Affiliations
                [1 ]Institute of Molecular Ecology and Evolution, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, China
                [2 ]School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
                University of Western Ontario, Canada
                Author notes

                Conceived and designed the experiments: BS XH SZ. Performed the experiments: BS XH. Analyzed the data: BS XH SJR. Contributed reagents/materials/analysis tools: SZ. Wrote the paper: BS SJR SZ. Bat species sampling: JZ.

                Article
                PONE-D-11-21443
                10.1371/journal.pone.0033197
                3320886
                22493665
                2d2a1c68-13f1-4cc0-870f-37611bd0441f
                Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 27 October 2011
                : 6 February 2012
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                Transmembrane Transport Proteins
                Computational Biology
                Sequence Analysis
                Evolutionary Biology
                Evolutionary Processes
                Adaptation
                Evolutionary Selection
                Natural Selection
                Forms of Evolution
                Microevolution
                Evolutionary Genetics
                Genetics
                Animal Genetics
                Molecular Cell Biology
                Signal Transduction
                Signaling in Cellular Processes
                Glucose Signaling

                Uncategorized
                Uncategorized

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