Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
    • JB Special Collection
    • JB Classic Spotlights
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JB
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Bacteriology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
    • JB Special Collection
    • JB Classic Spotlights
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JB
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Articles

A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock

Joseph S. Boyd, Ryan R. Cheng, Mark L. Paddock, Cigdem Sancar, Faruck Morcos, Susan S. Golden
P. J. Christie, Editor
Joseph S. Boyd
aCenter for Circadian Biology, University of California, San Diego, La Jolla, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan R. Cheng
bCenter for Theoretical Biological Physics, Rice University, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark L. Paddock
aCenter for Circadian Biology, University of California, San Diego, La Jolla, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cigdem Sancar
aCenter for Circadian Biology, University of California, San Diego, La Jolla, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Faruck Morcos
cDepartment of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan S. Golden
aCenter for Circadian Biology, University of California, San Diego, La Jolla, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. J. Christie
McGovern Medical School
Roles: Editor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JB.00235-16
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems.

IMPORTANCE Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins in vivo. Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks.

FOOTNOTES

    • Received 18 March 2016.
    • Accepted 27 June 2016.
    • Accepted manuscript posted online 5 July 2016.
  • Address correspondence to Faruck Morcos, faruckm{at}utdallas.edu, or Susan S. Golden, sgolden{at}ucsd.edu.
  • Citation Boyd JS, Cheng RR, Paddock ML, Sancar C, Morcos F, Golden SS. 2016. A combined computational and genetic approach uncovers network interactions of the cyanobacterial circadian clock. J Bacteriol 198:2439–2447. doi:10.1128/JB.00235-16.

  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/JB.00235-16.

  • Copyright © 2016, American Society for Microbiology. All Rights Reserved.
View Full Text
PreviousNext
Back to top
Download PDF
Citation Tools
A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock
Joseph S. Boyd, Ryan R. Cheng, Mark L. Paddock, Cigdem Sancar, Faruck Morcos, Susan S. Golden
Journal of Bacteriology Aug 2016, 198 (18) 2439-2447; DOI: 10.1128/JB.00235-16

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Bacteriology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock
(Your Name) has forwarded a page to you from Journal of Bacteriology
(Your Name) thought you would be interested in this article in Journal of Bacteriology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock
Joseph S. Boyd, Ryan R. Cheng, Mark L. Paddock, Cigdem Sancar, Faruck Morcos, Susan S. Golden
Journal of Bacteriology Aug 2016, 198 (18) 2439-2447; DOI: 10.1128/JB.00235-16
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • MATERIALS AND METHODS
    • RESULTS AND DISCUSSION
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

Cited By...

About

  • About JB
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #Jbacteriology

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0021-9193; Online ISSN: 1098-5530