The nucleotide-binding oligomerization domain proteins Nod1 and Nod2 are intracellular pathogen recognition receptors and members of the NLR family. Nod1 recognizes iE-DAP, a component of Gram-negative and some Gram-positive bacteria, whereas Nod2 recognizes MDP, a component of both Gram-negative and Gram-positive bacteria. In mammals, stimulation of Nod1 and Nod2 induces the production of pro-inflammatory cytokines IL-1b, IL-6 and TNF-a via the NF-kB pathway, suggesting an important role of Nod1 and Nod2 as innate immune sensors. Upon turkey genome analysis, we found a candidate sequence of the nod1 gene on turkey chromosome 6; however, there was no evidence of turkey nod2. Similarly, the current chicken and other avian genomes lack the nod2 gene, though they have a candidate nod1. The nod2 gene is located on human chromosome 16 and mouse chromosome 8 along with the nkd1, snx20 and cyld genes. A comparative analysis revealed that turkey chromosome 13 (MGA13) and chicken chromosome 11 (GGA11) are syntenic with human chromosome 16 and mouse chromosome 8, but they both lack nod2. The hagfish are the most primitive in vertebrate evolution, followed by lamprey, cart fish, bony fish, amphibians, reptiles, birds and mammals, respectively. The results of comparative genomics using CMap and GBrowse indicated no evidence of nod2 in the genomes of amphibians, reptiles and birds in terms of vertebrate evolution. In summary, comparative genomic analysis of model vertebrates showed that amphibians, reptiles and birds lack the intracellular innate immune sensor gene nod2, but an explanation for such findings is pending further analyses.