Science · 2009 · 665 citations · 5 references
Life SciencesGeneticsMolecular BiologyEnzyme MechanismEnzymologyMolecular EvolutionGenetic CodeRna Polymerase FunctionEnzymesExperimental Model TestingOligonucleotide SynthesisPopulation Doubling Time
Replicating RNA enzymes provide an experimental model of a genetic system, enabling construction of diverse systems to link selective outcomes to underlying genetic properties. Two RNA enzymes were engineered to cross‑replicate, each catalyzing the synthesis of the other from four oligonucleotide substrates. The cross‑replicating enzymes achieved self‑sustained exponential amplification with ~1‑hour doubling times, continued indefinitely, and recombinant replicators emerged to dominate competing populations.
An RNA enzyme that catalyzes the RNA-templated joining of RNA was converted to a format whereby two enzymes catalyze each other's synthesis from a total of four oligonucleotide substrates. These cross-replicating RNA enzymes undergo self-sustained exponential amplification in the absence of proteins or other biological materials. Amplification occurs with a doubling time of about 1 hour and can be continued indefinitely. Populations of various cross-replicating enzymes were constructed and allowed to compete for a common pool of substrates, during which recombinant replicators arose and grew to dominate the population. These replicating RNA enzymes can serve as an experimental model of a genetic system. Many such model systems could be constructed, allowing different selective outcomes to be related to the underlying properties of the genetic system.
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