Two Polymorphic Residues Account for the Differences in DNA Binding and Transcriptional Activation by NF-κB Proteins Encoded by Naturally Occurring Alleles in Nematostella vectensis

Abstract

The NF-κB family of transcription factors is activated in response to many environmental and biological stresses, and plays a key role in innate immunity across a broad evolutionary expanse of animals. A simple NF-κB pathway is present in the sea anemone Nematostella vectensis, an important model organism in the phylum Cnidaria. Nematostella has previously been shown to have two naturally occurring NF-κB alleles (Nv-NF-κB-C and Nv-NF-κB-S) that encode proteins with different DNA-binding and transactivation abilities. We show here that polymorphic residues 67 (Cys vs. Ser) and 269 (Ala vs. Glu) play complementary roles in determining the DNA-binding activity of the NF-κB proteins encoded by these two alleles and that residue 67 is primarily responsible for the difference in their transactivation ability. Phylogenetic analysis indicates that Nv-NF-κB-S is the derived allele, consistent with its restricted geographic distribution. These results define polymorphic residues that are important for the DNA-binding and transactivating activities of two naturally occurring variants of Nv-NF-κB. The implications for the appearance of the two Nv-NF-κB alleles in natural populations of sea anemones are discussed.

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Acknowledgments

This research was supported by grant MCB-0920461 from the National Science Foundation (J.R.F., T.D.G.) and ARRA supplement CA047763-22S3 (to T.D.G.). F.S.W. was supported by predoctoral grant by the Superfund Basic Research Program at Boston University 5 P42 ES07381, and F.S.W. and D.J.S. were supported by Warren-McLeod Fellowships. N.J. was supported by funds from the Boston University Undergraduate Research Opportunities Program. We thank Tristan Lubinski and Lauren Friedman for help with bioinformatic analyses and helpful discussions.

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Correspondence to Thomas D. Gilmore.

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Wolenski, F.S., Chandani, S., Stefanik, D.J. et al. Two Polymorphic Residues Account for the Differences in DNA Binding and Transcriptional Activation by NF-κB Proteins Encoded by Naturally Occurring Alleles in Nematostella vectensis . J Mol Evol 73, 325–336 (2011). https://doi.org/10.1007/s00239-011-9479-7

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Keywords

  • NF-κB
  • Nematostella
  • Polymorphism
  • Evolution
  • DNA binding
  • Transactivation