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Title: Evolution of context dependent regulation by expansion of feast/famine regulatory proteins

Expansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment. We mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively. This study provides a systems perspective into the evolutionary processmore » by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism.« less
 [1] ;  [2] ;  [1] ;  [2] ;  [2] ;  [1] ;  [1] ;  [1] ;  [3] ;  [4]
  1. Inst. for Systems Biology, Seattle, WA (United States)
  2. Inst. for Systems Biology, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States). Molecular and Cellular Biology Program
  3. Univ. of California, Davis, CA (United States). Dept. of Biomedical Engineering and Genome Center
  4. Inst. for Systems Biology, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States). Molecular and Cellular Biology Program, Dept. of Microbiology, and Dept. of Biology
Publication Date:
OSTI Identifier:
Grant/Contract Number:
AC02-05CH11231; FG02-04ER64685; FG02-07ER64327; FG02-08ER64685; AC05-06OR23100
Accepted Manuscript
Journal Name:
BMC Systems Biology
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 1752-0509
BioMed Central
Research Org:
Inst. for Systems Biology, Seattle, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Contributing Orgs:
ENIGMA Consortium
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES transcription factor; expansion; systems biology