title: Two alleles of NF-kappaB in the sea anemone Nematostella vectensis are widely dispersed in nature and encode proteins with distinct activities.
abstract: BACKGROUND
  NF-kappaB is an evolutionarily conserved transcription factor that controls the expression of genes involved in many key organismal processes, including innate immunity, development, and stress responses. NF-kappaB proteins contain a highly conserved DNA-binding/dimerization domain called the Rel homology domain.
  
  
  RESULTS
  We characterized two NF-kappaB alleles in the sea anemone Nematostella vectensis that differ at nineteen single-nucleotide polymorphisms (SNPs). Ten of these SNPs result in amino acid substitutions, including six within the Rel homology domain. Both alleles are found in natural populations of Nematostella. The relative abundance of the two NF-kappaB alleles differs between populations, and departures from Hardy-Weinberg equilibrium within populations indicate that the locus may be under selection. The proteins encoded by the two Nv-NF-kappaB alleles have different molecular properties, in part due to a Cys/Ser polymorphism at residue 67, which resides within the DNA recognition loop. In nearly all previously characterized NF-kappaB proteins, the analogous residue is fixed for Cys, and conversion of human RHD proteins from Cys to Ser at this site has been shown to increase DNA-binding ability and increase resistance to inhibition by thiol-reactive compounds. However, the naturally-occurring Nematostella variant with Cys at position 67 binds DNA with a higher affinity than the Ser variant. On the other hand, the Ser variant activates transcription in reporter gene assays more effectively, and it is more resistant to inhibition by a thiol-reactive compound. Reciprocal Cys<->Ser mutations at residue 67 of the native Nv-NF-kappaB proteins affect DNA binding as in human NF-kappaB proteins, e.g., a Cys->Ser mutation increases DNA binding of the native Cys variant.
  
  
  CONCLUSIONS
  These results are the first demonstration of a naturally occurring and functionally significant polymorphism in NF-kappaB in any species. The functional differences between these alleles and their uneven distribution in the wild suggest that different genotypes could be favored in different environments, perhaps environments that vary in their levels of peroxides or thiol-reactive compounds.
authors.affiliation: Department of Biology, Boston University, Boston, Massachusetts, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Sullivan
authors.forename: Francis S
authors.initials: FS
authors.lastname: Wolenski
authors.forename: Adam M
authors.initials: AM
authors.lastname: Reitzel
authors.forename: Courtney E
authors.initials: CE
authors.lastname: French
authors.forename: Nikki
authors.initials: N
authors.lastname: Traylor-Knowles
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Gilmore
authors.forename: John R
authors.initials: JR
authors.lastname: Finnerty
mesh_terms: D000483:Alleles; D000818:Animals; D003545:Cysteine / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D019281:Dimerization; D006239:Haplotypes; D008957:Models, Genetic; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012615:Sea Anemones / Q000235:genetics* / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D051996:Transcription Factor RelA / Q000737:chemistry
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA; D012694:Serine; D004247:DNA; D003545:Cysteine