Forty Years of In Vitro Evolution


  • Gerald F. Joyce Prof.

    1. Departments of Chemistry and Molecular Biology
    2. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2943
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  • The cover picture shows a photograph of Sol Spiegelman (1974; courtesy of the Albert and Mary Lasker Foundation) next to the crystal structure of an RNA enzyme that catalyzes the RNA-templated joining of RNA;81 white: nucleotide at the ligation junction, purple sphere: Mg2+ ion thought to be involved in catalysis (courtesy of Michael Robertson and William Scott). The background shows a reconstructed space-time image of traveling waves of evolving Qβ RNA within a capillary tube;21 horizontal axis: position along the capillary, vertical axis: fixed time intervals (from top to bottom), color gradation: concentration of RNA.


It has been 40 years since Spiegelman and co-workers demonstrated how RNA molecules can be evolved in the test tube. This result established Darwinian evolution as a chemical process and paved the way for the many directed evolution experiments that followed. Chemists can benefit from reflecting on Spiegelman's studies and the subsequent advances, which have taken the field to the brink of the generation of life itself in the laboratory. This Review summarizes the concepts and methods for the directed evolution of RNA molecules in vitro.