Directed evolution of a genetic circuit

Yohei Yokobayashi, Ron Weiss, Frances H. Arnold

Research output: Contribution to journalArticlepeer-review

330 Scopus citations


The construction of artificial networks of transcriptional control elements in living cells represents a new frontier for biological engineering. However, biological circuit engineers will have to confront their inability to predict the precise behavior of even the most simple synthetic networks, a serious shortcoming and challenge for the design and construction of more sophisticated genetic circuitry in the future. We propose a combined rational and evolutionary design strategy for constructing genetic regulatory circuits, an approach that allows the engineer to fine-tune the biochemical parameters of the networks experimentally in vivo. By applying directed evolution to genes comprising a simple genetic circuit, we demonstrate that a nonfunctional circuit containing improperly matched components can evolve rapidly into a functional one. In the process, we generated a library of genetic devices with a range of behaviors that can be used to construct more complex circuits.

Original languageEnglish (US)
Pages (from-to)16587-16591
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 24 2002
Externally publishedYes


  • Biocomputation
  • Molecular evolution
  • Random mutagenesis
  • Repressor gene regulation

ASJC Scopus subject areas

  • Genetics
  • General


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