Two Different Complement C3 Genes in Crocodilians

Crocodilians exhibit powerful antibacterial activities in their tissues and blood. The activities have been partially attributed to the presence of a potent serum complement system of proteins that acts in a nonspecific manner to kill bacteria. Complement activation involves activation of complement C3, a component with broad immune and regulatory function. We searched the crocodilian genomes (Alligator mississippiensis, Crocodylus porosus, and Gavialis gangeticus) for complement C3, and found two genes that code for isoforms with quite different sequences. Birds and mammals express only a single isoform of the complement C3 protein. Some snakes were shown to have two C3 genes; however, these encode proteins with very similar amino acid sequences. To date, only fishes were reported to express complement C3 isoforms with diversity similar to that of the crocodilian forms. Phylogenetic analysis suggests the gene duplication leading to the two crocodilian paralogs probably occurred within the order Crocodylia. Both contain signal sequences, putative internal thioesters, potential N-glycosylation sites, and functional domains that would allow them to interact with complement receptors and other complement system components. As has been suggested with fishes, the expression of multiple functional C3 isoforms may allow crocodilians to respond to a broad spectrum of immunological insult.