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.
UMass Chan Affiliations
Schiffer LabDepartment of Microbiology and Physiological Systems
Department of Medicine
Program in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2018-04-13Keywords
deep mutational scanningexperimental 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
Metadata
Show full item recordAbstract
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.2018.02.009Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48881PubMed ID
29466705Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.jmb.2018.02.009