Directed evolution of a genetic circuit

Yohei Yokobayashi, Ron Weiss, Frances H. Arnold

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

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
Volume99
Issue number26
DOIs
StatePublished - Dec 24 2002
Externally publishedYes

Fingerprint

Bioengineering
Molecular Evolution
Gene Regulatory Networks
Libraries
Equipment and Supplies
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Directed evolution of a genetic circuit. / Yokobayashi, Yohei; Weiss, Ron; Arnold, Frances H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 26, 24.12.2002, p. 16587-16591.

Research output: Contribution to journalArticle

Yokobayashi, Yohei ; Weiss, Ron ; Arnold, Frances H. / Directed evolution of a genetic circuit. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 26. pp. 16587-16591.
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