Synthetic Evolving Systems that Implement a User-Specified Genetic Code of Arbitrary Design

SummaryA synthetic genetic system, based on cross-replicating RNA enzymes, provides a means to evaluate alternative genetic codes that relate heritable information to corresponding molecular function. A special implementation of encoded combinatorial chemistry was used to construct complex populations of cross-replicating RNA enzymes in accordance with a user-specified code that relates genotype and phenotype on a molecule-by-molecule basis. The replicating enzymes were made to undergo self-sustained Darwinian evolution, resulting in the emergence of the most advantageous variants. These included both highly active enzymes that sustained the population as a whole and poorly active enzymes that survived as parasites of the active molecules. This evolutionary outcome was a consequence of the information capacity and fidelity of the genetic code, suggesting how these parameters should be adjusted to implement codes tailored to particular applications.

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► Populations of replicating RNAs were constructed by encoded combinatorial chemistry
► The RNAs evolve based on a heritable genotype and corresponding catalytic phenotype
► Genotype and phenotype are related by a user-specified genetic code
► The evolved enzymes included both highly active catalysts and molecular parasites