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Journal of Bacteriology, September 2005, p. 6430-6442, Vol. 187, No. 18
0021-9193/05/$08.00+0     doi:10.1128/JB.187.18.6430-6442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Positive Autoregulation of cI Is a Dispensable Feature of the Phage Gene Regulatory Circuitry

Christine B. Michalowski¹ and John W. Little^1,2*

Department of Biochemistry and Molecular Biophysics,¹ Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721²

Received 14 April 2005/ Accepted 24 June 2005

Complex gene regulatory circuits contain many features that are likely to contribute to their operation. It is unclear, however, whether all these features are necessary for proper circuit behavior or whether certain ones are refinements that make the circuit work better but are dispensable for qualitatively normal behavior. We have addressed this question using the phage regulatory circuit, which can persist in two stable states, the lytic state and the lysogenic state. In the lysogenic state, the CI repressor positively regulates its own expression by stimulating transcription from the P_RM promoter. We tested whether this feature is an essential part of the regulatory circuitry. Several phages with a cI mutation preventing positive autoregulation and an up mutation in the P_RM promoter showed near-normal behavior. We conclude that positive autoregulation is not necessary for proper operation of the circuitry and speculate that it serves a partially redundant function of stabilizing a bistable circuit, a form of redundancy we term "circuit-level redundancy." We discuss our findings in the context of a two-stage model for evolution and elaboration of regulatory circuits from simpler to more complex forms.

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* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biophysics, Life Sciences South Bldg., 1007 E. Lowell St., University of Arizona, Tucson, AZ 85721. Phone: (520) 621-5629. Fax: (520) 621-3709. E-mail: jlittle{at}email.arizona.edu.

Supplemental material for this article may be found at http://jb.asm.org/.

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Journal of Bacteriology, September 2005, p. 6430-6442, Vol. 187, No. 18
0021-9193/05/$08.00+0     doi:10.1128/JB.187.18.6430-6442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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