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

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.