Phylogenomics of caspase-activated DNA fragmentation factor.
The degradation of nuclear DNA by DNA fragmentation factor (DFF) is a key step in apoptosis of mammalian cells. Using comparative genomics, we have here determined the evolutionary history of the genes encoding the two DFF subunits, DFFA (also known as ICAD) and DFFB (CAD). Orthologs of DFFA and DFFB were identified in Nematostella vectensis, a representative of the primitive metazoan clade cnidarians, and in various vertebrates and insects, but not in representatives of urochordates, echinoderms, and nematodes. The domains mediating the interaction of DFFA and DFFB, a caspase cleavage site in DFFA, and the amino acid residues critical for endonuclease activity of DFFB were conserved in Nematostella. These findings suggest that DFF has been a part of the primordial apoptosis system of the eumetazoan common ancestor and that the ancient cell death machinery has degenerated in several evolutionary lineages, including the one leading to the prototypical apoptosis model, Caenorhabditis elegans.
Eckhart
Leopold
L
Department of Dermatology, Medical University of Vienna, A-1090 Vienna, Austria. leopold.eckhart@meduniwien.ac.at
Fischer
Heinz
H
Tschachler
Erwin
E
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D020169:Caspases / Q000378:metabolism*; D017124:Conserved Sequence; D053938:DNA Fragmentation; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012615:Sea Anemones / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D051017:Apoptosis Regulatory Proteins; D020033:Protein Isoforms; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D020169:Caspases