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    Synonymous Mutations at the Beginning of the Influenza A Virus Hemagglutinin Gene Impact Experimental Fitness

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    Authors
    Canale, Aneth S.
    Venev, Sergey V.
    Whitfield, Troy W.
    Caffrey, Daniel R.
    Marasco, Wayne A.
    Schiffer, Celia A.
    Kowalik, Timothy F.
    Jensen, Jeffrey D.
    Finberg, Robert W.
    Zeldovich, Konstantin B.
    Wang, Jennifer P.
    Bolon, Daniel N.
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    UMass Chan Affiliations
    Schiffer Lab
    Department of Microbiology and Physiological Systems
    Department of Medicine
    Program in Bioinformatics and Integrative Biology
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2018-04-13
    Keywords
    deep mutational scanning
    experimental evolution
    influenza A virus
    selection
    synonymous mutations
    Biochemistry
    Ecology and Evolutionary Biology
    Genetic Phenomena
    Medicinal Chemistry and Pharmaceutics
    Medicinal-Pharmaceutical Chemistry
    Molecular Biology
    Nucleic Acids, Nucleotides, and Nucleosides
    Structural Biology
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    Link to Full Text
    https://doi.org/10.1016/j.jmb.2018.02.009
    Abstract
    The fitness effects of synonymous mutations can provide insights into biological and evolutionary mechanisms. We analyzed the experimental fitness effects of all single-nucleotide mutations, including synonymous substitutions, at the beginning of the influenza A virus hemagglutinin (HA) gene. Many synonymous substitutions were deleterious both in bulk competition and for individually isolated clones. Investigating protein and RNA levels of a subset of individually expressed HA variants revealed that multiple biochemical properties contribute to the observed experimental fitness effects. Our results indicate that a structural element in the HA segment viral RNA may influence fitness. Examination of naturally evolved sequences in human hosts indicates a preference for the unfolded state of this structural element compared to that found in swine hosts. Our overall results reveal that synonymous mutations may have greater fitness consequences than indicated by simple models of sequence conservation, and we discuss the implications of this finding for commonly used evolutionary tests and analyses.
    Source

    J Mol Biol. 2018 Apr 13;430(8):1098-1115. doi: 10.1016/j.jmb.2018.02.009. Epub 2018 Feb 18. Link to article on publisher's site

    DOI
    10.1016/j.jmb.2018.02.009
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48881
    PubMed ID
    29466705
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jmb.2018.02.009
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