Development Genes and Evolution

, Volume 217, Issue 1, pp 63–72 | Cite as

Rel homology domain-containing transcription factors in the cnidarian Nematostella vectensis

  • James C. Sullivan
  • Demetrios Kalaitzidis
  • Thomas D. Gilmore
  • John R. FinnertyEmail author
Sequence Corner


The Rel/NF-κB and NFAT families of transcription factors are related through an N-terminal DNA-binding domain called the Rel Homology domain (RHD). Neither the RHD nor the NF-κB pathway has been identified in a basal (i.e., nonbilaterian) animal phylum. Using genomic and cDNA databases, we have identified two RHD domain-containing proteins from the cnidarian Nematostella vectensis: an NF-κB-like protein (Nv-NF-κB) and an NFAT-like protein (Nv-NFAT). The gene structure and RHD predicted amino acid sequence of Nv-nfkb are similar to those of the vertebrate NF-κB p50/p52 proteins, whereas the sequence of Nv-NFAT allows only ambiguous assignment to the NFAT family. Nv-NF-κB lacks the C-terminal IκB-like sequences present in all other NF-κB proteins. There are, however, two IκB-like genes in Nematostella encoded by loci distinct from Nv-nfkb. The separate nfkb and ikb genes of Nematostella may reflect the ancestral metazoan condition, suggesting that a gene fusion event created the nfkb genes in Drosophila and vertebrates. Nematostella also has genes that encode upstream and downstream components of the vertebrate NF-κB signaling pathway. Upstream components include Toll- and tumor necrosis-like receptors and ligands, adaptor proteins (Trafs, Myd88), caspases, and a TBK-like kinase. Downstream components include the NF-κB coactivator protein Bcl-3 and several NF-κB target genes. These results demonstrate that RHD-containing transcription factors and associated pathways are evolutionarily more ancient than previously known. Moreover, they suggest models for the evolutionary diversification of the insect and vertebrate Rel/NF-κB/IκB and NFAT gene families and suggest that cnidarians possess an NF-κB-regulated developmental or stress response pathway.


NF-kappaB NFAT IkappaB Rel homology domain Evolution 



This research was supported by NIH research grant CA47763 (TDG), NSF grant IBN-0212773 (JRF), and BU SPRInG grant 20-202-8103-9. The NF-κB website ( was utilized for sequence retrieval.

Supplementary material

427_2006_111_MOESM1_ESM.doc (32 kb)
Table S1 Nomenclature of RHD and IκB-like proteins (DOC 32 kb)
427_2006_111_MOESM2_ESM.doc (48 kb)
Table S2 Genbank accession numbers and taxon ID’s of taxa used in phylogenetic analyses (DOC 48 kb)
427_2006_111_Fig1_ESM.jpg (454 kb)
Fig. S1

Alignment used in phylogenetic analyses of the IκB family represented in Fig. 4 (JPEG 465 kb)

427_2006_111_Fig1_ESM.tif (8.7 mb)
High resolution image file (TIFF 9,157 kb)


  1. Darling JA, Reitzel AR, Burton PM, Mazza ME, Ryan JF, Sullivan JC, Finnerty JR (2005) Rising starlet: the starlet sea anenome, Nematostella vectensis. BioEssays 27:211–221PubMedCrossRefGoogle Scholar
  2. Felsenstein J (2004) Inferring phylogenies. Sinauer Associates, Sunderland, MassachusettsGoogle Scholar
  3. Finnerty JR, Pang K, Burton P, Paulson D, Martindale MQ (2004) Homology of bilateral symmetry in Cnidaria and Bilateria: axial expression of Hox genes and Dpp in the sea anemone Nematostella. Science 304:1335–1337PubMedCrossRefGoogle Scholar
  4. Graef IA, Gastier JM, Francke U, Crabtree GR (2001) Evolutionary relationships among Rel domains indicate functional diversification by recombination. Proc Natl Acad Sci USA 98:5740–5745PubMedCrossRefGoogle Scholar
  5. Hayden MS, Ghosh S (2004) Signaling to NF-κB. Genes Dev 18:2195–2224PubMedCrossRefGoogle Scholar
  6. Huguet C, Crepieux P, Laudet V (1997) Rel/NF-κB transcription factors and the IκB inhibitors: evolution from a unique common ancestor. Oncogene 15:2965–2974PubMedCrossRefGoogle Scholar
  7. Kortschak RD, Samuel G, Saint R, Miller DJ (2003) EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates. Curr Biol 13:2190–2195PubMedCrossRefGoogle Scholar
  8. Kusserow A, Pang K, Sturm C, Hrouda M, Lentfer J, Schmidt HA, Technau U, von Haeseler A, Hobayer B, Martindale MQ, Holstein TW (2005) Unexpected complexity of the Wnt gene family in a sea anemone. Nature 433:156–160PubMedCrossRefGoogle Scholar
  9. Macian F (2005) NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 5:472–484PubMedCrossRefGoogle Scholar
  10. Medina M, Collins AG, Silberman JD, Sogin ML (2001) Evaluating hypotheses of basal animal phylogeny using complete sequences of large and small subunit rRNA. Proc Natl Acad Sci USA 98:9707–9712PubMedCrossRefGoogle Scholar
  11. Rogozin IB, Wolf YI, Sorokin AV, Mirkin BG, Koonin EV (2003) Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 13:1512–1517PubMedCrossRefGoogle Scholar
  12. Ryan JF, Burton PM, Mazza ME, Kwong GK, Mullikin JC, Finnerty JR (2006) The cnidarian–bilaterian ancestor possessed at least 56 homeoboxes. Evidence from the starlet sea anemone, Nematostella vectensis. Genome Biol 7;R64Google Scholar
  13. Sullivan JC, Ryan JF, Watson JA, Webb J, Mullikin JC, Rokhsar D, Finnerty JR (2006) StellaBase: the Nematostella vectensis genomics database. Nucleic Acids Res 34:D495–D499PubMedCrossRefGoogle Scholar
  14. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24:4876–4882CrossRefGoogle Scholar
  15. Technau U, Rudd S, Maxwell P, Gordon PMK, Saina M, Grasso LC, Hayward DC, Sensen CW, Saint R, Holstein TW, Ball EE, Miller DJ (2005) Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet 121:633–639CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • James C. Sullivan
    • 1
  • Demetrios Kalaitzidis
    • 2
  • Thomas D. Gilmore
    • 1
  • John R. Finnerty
    • 1
    Email author
  1. 1.Department of BiologyBoston UniversityBostonUSA
  2. 2.Hematology–Oncology/Cancer Biology Program, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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