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Evolution of robustness to protein mistranslation by accelerated protein turnover

ABSTRACT: To investigate how organisms mitigate the deleterious effects of mistranslation during evolution, a mutant tRNA was expressed in S. cerevisiae. The expression of Candida Ser-tRNACAG from a low copy plasmid in S. cerevisiae promoted mistranslation events by random incorporation of both serine and leucine at CUG codons. As mistranslation causes an overload of the protein quality pathways, it disrupts cellular protein homeostasis leading to a major fall in fitness. Laboratory evolutionary experiments were performed to study whether the fitness cost of mistranslation can be lowered. We also wanted to identify the cost-reduction strategy: reducing the frequencies of errors (mitigation), or increasing tolerance to errors (robustness), either by global or local activities.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE65718 | GEO | 2015/11/06

SECONDARY ACCESSION(S): PRJNA274784

REPOSITORIES: GEO

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Evolution of robustness to protein mistranslation by accelerated protein turnover

Project description:To investigate how organisms mitigate the deleterious effects of mistranslation during evolution, a mutant tRNA was expressed in S. cerevisiae. The expression of Candida Ser-tRNACAG from a low copy plasmid in S. cerevisiae promoted mistranslation events by random incorporation of both serine and leucine at CUG codons. As mistranslation causes an overload of the protein quality pathways, it disrupts cellular protein homeostasis leading to a major fall in fitness. Laboratory evolutionary experiments were performed to study whether the fitness cost of mistranslation can be lowered. We also wanted to identify the cost-reduction strategy: reducing the frequencies of errors (mitigation), or increasing tolerance to errors (robustness), either by global or local activities. Gene expression was measured in the ancestor (non-evolved) lineage in two different situations: 1) carrying an empty vector and 2) expressing the mutant Ser-tRNACAG. Gene expression was also measured in three ambiguously evolved lineages (B3, D11, H9) in both situations (carrying an empty vector and expressing the mutant tRNA). Three independent experiments were performed for each lineage. Non-evolved strain with empty vector was used as control sample.

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Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover.

Project description: Not available

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Project description:The fungal pathogen Candida albicans and other pathogens of the CTG clade reassigned the leucine CUG codon to serine and tolerate highly variable levels of both serine and leucine at CUG positions in response to environmental cues. Previous studies found that increased leucine misincorporation levels enhance resistance to drugs but the underlying mechanisms are not known. To clarify the biological role of this tuneable codon ambiguity, we evolved C. albicans strains engineered to mistranslate CUG at elevated levels, in the presence and absence of the antifungal drug fluconazole

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