Mistranslation: from adaptations to applications

Kyle S Hoffman; Patrick O'Donoghue; Christopher J Brandl

doi:10.1016/j.bbagen.2017.01.031

Mistranslation: from adaptations to applications

Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt B):3070-3080. doi: 10.1016/j.bbagen.2017.01.031. Epub 2017 Jan 30.

Authors

Kyle S Hoffman¹, Patrick O'Donoghue², Christopher J Brandl³

Affiliations

¹ Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
² Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada; Department of Chemistry, The University of Western Ontario, London, ON N6A 5B7, Canada.
³ Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: cbrandl@uwo.ca.

PMID: 28153753
DOI: 10.1016/j.bbagen.2017.01.031

Abstract

Background: The conservation of the genetic code indicates that there was a single origin, but like all genetic material, the cell's interpretation of the code is subject to evolutionary pressure. Single nucleotide variations in tRNA sequences can modulate codon assignments by altering codon-anticodon pairing or tRNA charging. Either can increase translation errors and even change the code. The frozen accident hypothesis argued that changes to the code would destabilize the proteome and reduce fitness. In studies of model organisms, mistranslation often acts as an adaptive response. These studies reveal evolutionary conserved mechanisms to maintain proteostasis even during high rates of mistranslation.

Scope of review: This review discusses the evolutionary basis of altered genetic codes, how mistranslation is identified, and how deviations to the genetic code are exploited. We revisit early discoveries of genetic code deviations and provide examples of adaptive mistranslation events in nature. Lastly, we highlight innovations in synthetic biology to expand the genetic code.

Major conclusions: The genetic code is still evolving. Mistranslation increases proteomic diversity that enables cells to survive stress conditions or suppress a deleterious allele. Genetic code variants have been identified by genome and metagenome sequence analyses, suppressor genetics, and biochemical characterization.

General significance: Understanding the mechanisms of translation and genetic code deviations enables the design of new codes to produce novel proteins. Engineering the translation machinery and expanding the genetic code to incorporate non-canonical amino acids are valuable tools in synthetic biology that are impacting biomedical research. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.

Keywords: Adaptive response; Evolution; Genetic code; Mistranslation; Transfer RNA; Translation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adaptation, Biological / genetics*
Animals
Codon / genetics*
Evolution, Molecular
Genetic Code*
Humans
Mutation / physiology*
Polymorphism, Genetic / physiology
Protein Biosynthesis / genetics*
Protein Engineering* / methods
Protein Engineering* / trends

Substances

Codon