Matches in SemOpenAlex for { <https://semopenalex.org/work/W2953449905> ?p ?o ?g. }
- W2953449905 abstract "ABSTRACT One challenge in engineering organisms is guaranteeing system behavior over many generations. Spontaneous mutations that arise before or during use can impact heterologous genetic functions, disrupt system integration, or change organism phenotype. Here, we propose restructuring the genetic code itself such that all point mutations in protein-coding sequences are selected against. Synthetic genetic systems so-encoded should “fail safely” in response to many individual spontaneous mutations. We designed a family of such fail-safe codes and analyzed their expected effect on the evolution of engineered organisms via simulation. We predict that fail-safe codes supporting expression of 20 or 15 amino acids could slow the evolution of proteins in so-encoded organisms to 30% or 0% the rate of standard-code organisms, respectively. We also designed quadruplet-codon codes that should be capable of encoding at least 20 amino acids while ensuring all single point mutations in protein-coding sequences are selected against. We show by in vitro experiments that a reduced set of 21 tRNA is capable of expressing a protein whose coding sequence is recoded to use a fail-safe code, whereas a standard-code encoding is not expressed. Our work suggests that a rationally depleted but otherwise natural translation system should yield biological systems with intrinsically reduced evolutionary capacity, and that so-encoded hypoevolvable organisms might be less likely to invade new niches or outcompete native populations." @default.
- W2953449905 created "2019-07-12" @default.
- W2953449905 creator A5034965134 @default.
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- W2953449905 date "2019-07-08" @default.
- W2953449905 modified "2023-09-23" @default.
- W2953449905 title "Synthetic Genetic Codes Designed to Hinder Evolution" @default.
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- W2953449905 doi "https://doi.org/10.1101/695569" @default.
- W2953449905 hasPublicationYear "2019" @default.
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