title: Synthetic evolving systems that implement a user-specified genetic code of arbitrary design.
abstract: A 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Sczepanski
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Joyce
mesh_terms: D001483:Base Sequence; D019020:Directed Molecular Evolution; D005815:Genetic Code; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016337:RNA, Catalytic