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Journal of Bacteriology, March 2005, p. 1901-1912, Vol. 187, No. 6
0021-9193/05/$08.00+0     doi:10.1128/JB.187.6.1901-1912.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Percolation of the Phd Repressor-Operator Interface

Xueyan Zhao and Roy David Magnuson*

Department of Biological Sciences, University of Alabama, Huntsville, Alabama

Received 4 October 2004/ Accepted 6 December 2004

Transcription of the P1 plasmid addiction operon, a prototypical toxin-antitoxin system, is negatively autoregulated by the products of the operon. The Phd repressor-antitoxin protein binds to 8-bp palindromic Phd-binding sites in the promoter region and thereby represses transcription. The toxin, Doc, mediates cooperative interactions between adjacent Phd-binding sites and thereby enhances repression. Here, we describe a homologous operon from Salmonella enterica serovar Typhimurium which has the same pattern of regulation but an altered repressor-operator specificity. This difference in specificity maps to the seventh amino acid of the repressor and to the symmetric first and eighth positions of the corresponding palindromic repressor-binding sites. Thus, the repressor-operator interface has coevolved so as to retain the interaction while altering the specificity. Within an alignment of homologous repressors, the seventh amino acid of the repressor is highly variable, indicating that evolutionary changes in repressor specificity may be common in this protein family. We suggest that the robust properties of the negative feedback loop, the fuzzy recognition in the operator-repressor interface, and the duplication and divergence of the repressor-binding sites have facilitated the speciation of this repressor-operator interface. These three features may allow the repressor-operator system to percolate within a nearly neutral network of single-step mutations without the necessity of invoking simultaneous mutations, low-fitness intermediates, or other improbable or rate-limiting mechanisms.


* Corresponding author. Mailing address: Department of Biological Sciences, University of Alabama in Huntsville, Wilson Hall Room 258, 301 Sparkman Drive, Huntsville, AL 35758. Phone: (256) 824-6094. Fax: (256) 824-6305. E-mail: magnusr{at}.uah.edu.


Journal of Bacteriology, March 2005, p. 1901-1912, Vol. 187, No. 6
0021-9193/05/$08.00+0     doi:10.1128/JB.187.6.1901-1912.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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