title: Exposing synonymous mutations.
abstract: Synonymous codon changes, which do not alter protein sequence, were previously thought to have no functional consequence. Although this concept has been overturned in recent years, there is no unique mechanism by which these changes exert biological effects. A large repertoire of both experimental and bioinformatic methods has been developed to understand the effects of synonymous variants. Results from this body of work have provided global insights into how biological systems exploit the degeneracy of the genetic code to control gene expression, protein folding efficiency, and the coordinated expression of functionally related gene families. Although it is now clear that synonymous variants are important in a variety of contexts, from human disease to the safety and efficacy of therapeutic proteins, there is no clear consensus on the approaches to identify and validate these changes. Here, we review the diverse methods to understand the effects of synonymous mutations.
authors: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Electronic address: ryan.hunt@fda.hhs.gov.
authors: Ryan C
authors: RC
authors: Hunt
authors: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors: Vijaya L
authors: VL
authors: Simhadri
authors: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors: Matthew
authors: M
authors: Iandoli
authors: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Electronic address: zuben.sauna@fda.hhs.gov.
authors: Zuben E
authors: ZE
authors: Sauna
authors: Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Electronic address: chava.kimchi-sarfaty@fda.hhs.gov.
authors: Chava
authors: C
authors: Kimchi-Sarfaty
mesh_terms: D000818:Animals; D003062:Codon; D019295:Computational Biology / Q000379:methods; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D066263:Protein Aggregation, Pathological / Q000235:genetics; D014176:Protein Biosynthesis; D011487:Protein Conformation; D055550:Protein Stability; D058767:Protein Unfolding; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D003062:Codon; D012333:RNA, Messenger
keywords: codon usage; mRNA structure; synonymous mutation; synonymous single nucleotide polymorphism; translation speed