Evolving Mistranslating tRNAs Through a Phenotypically Ambivalent Intermediate in Saccharomyces cerevisiae

Matthew D BergChristopher J Brandl


The genetic code converts information from nucleic acid into protein. The genetic code was thought to be immutable, yet many examples in nature indicate that variations to the code provide a selective advantage. We used a sensitive selection system involving suppression of a deleterious allele (tti2-L187P) in Saccharomyces cerevisiae to detect mistranslation and identify mechanisms that allow genetic code evolution. Though tRNASer containing a proline anticodon (UGG) is toxic, using our selection system we identified four tRNASerUGG variants, each with a single mutation, that mistranslate at a tolerable level. Mistranslating tRNALeuUGG variants were also obtained, demonstrating the generality of the approach. We characterized two of the tRNASerUGG variants. One contained a G26A mutation, which reduced cell growth to 70% of the wild-type rate, induced a heat shock response, and was lost in the absence of selection. The reduced toxicity of tRNASerUGG-G26A is likely through increased turnover of the tRNA, as lack of methylation at G26 leads to degradation via the rapid tRNA decay pathway. The second tRNASerUGG variant, with a G9A mutation, had minimal effect on cell growth, was relatively stable in cells, and gave rise to less of ...Continue Reading


Sep 22, 2017·RNA Biology·Jeremy T LantPatrick O'Donoghue
Jan 16, 2019·The Journal of Biological Chemistry·Jeremy T LantPatrick O'Donoghue
Aug 14, 2019·RNA Biology·Matthew D BergChristopher J Brandl
Sep 6, 2019·Genetics·Matthew D BergChristopher J Brandl
Sep 10, 2020·RNA Biology·Matthew D Berg, Christopher J Brandl
Jun 2, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Yanrui ZhuChrisopher J Brandl
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Related Concepts

Saccharomyces cerevisiae Proteins
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