Methods for analyzing the evolutionary relationship of NF-κB proteins using free, web-driven bioinformatics and phylogenetic tools.
Phylogenetic analysis enables one to reconstruct the functional evolution of proteins. Current understanding of NF-κB signaling derives primarily from studies of a relatively small number of laboratory models-mainly vertebrates and insects-that represent a tiny fraction of animal evolution. As such, NF-κB has been the subject of limited phylogenetic analysis. The recent discovery of NF-κB proteins in "basal" marine animals (e.g., sponges, sea anemones, corals) and NF-κB-like proteins in non-metazoan lineages extends the origin of NF-κB signaling by several hundred million years and provides the opportunity to investigate the early evolution of this pathway using phylogenetic approaches. Here, we describe a combination of bioinformatic and phylogenetic analyses based on menu-driven, open-source computer programs that are readily accessible to molecular biologists without formal training in phylogenetic methods. These phylogenetically based comparisons of NF-κB proteins are powerful in that they reveal deep conservation and repeated instances of parallel evolution in the sequence and structure of NF-κB in distant animal groups, which suggest that important functional constraints limit the evolution of this protein.
Department of Biology, Boston University, 5 Cummington Mall, Boston, MA, 02215, USA, jrf3@bu.edu.
John R
JR
Finnerty
Thomas D
TD
Gilmore
D020816:Amino Acid Motifs; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D030541:Databases, Genetic; D019143:Evolution, Molecular; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D012984:Software; D064878:Web Browser
D016328:NF-kappa B