Evolutionary relationships of vertebrate NACHT domain-containing proteins.

Phylogenetic analyses of conserved [neuronal apoptosis inhibitory protein (NAIP), MHC class II transcription activator (CIITA), incompatibility locus protein from Podospora anserina (HET-E), and telomerase-associated protein (TP1)] (NACHT) domains were used to reconstruct the evolutionary history of vertebrate NACHT-containing proteins. The results supported the hypothesis that NOD3 is basal to the other NACHT-containing proteins found in tetrapods. The latter formed two strongly supported clusters or subfamilies, here designated NALP and nucleotide-binding oligomerization domain (NOD). The presence of apparent bony fish orthologs of NOD3 and CIITA supported the hypothesis that the origin of these molecules predates the origin of tetrapods, and the presence of avian sequences in both NALP and NOD clusters supported the origin of these subfamilies before the bird-mammal divergence. However, the extensive diversification of the NALP subfamily seen in mammals evidently occurred within the mammalian lineage. Both NALP and NOD subfamilies include members with differential expression in the antigen-presenting cells of the immune system, and the phylogenetic analyses supported the hypothesis that this expression pattern has evolved independently more than once in each of these subfamilies.