Occurrence of structural specialization of the serine protease domain of complement factor B at the emergence of jawed vertebrates and adaptive immunity

Mammalian complement factor B (Bf) and C2 are two central enzymes involved in complement activation, and constitute the catalytic subunit of C3 convertases of the alternative and classical pathways, respectively. They share the same domain structure: from the N-terminus, three short consensus repeat domains, one von Willebrand factor type A domain, and one serine protease domain. Consequently, the Bf and C2 genes seem to have been generated from a common ancestor by gene duplication. Phylogenetic analysis of Bf and C2 indicated that invertebrate sea urchin Bf and cyclostome lamprey Bf represent a common ancestral state of Bf and C2, whereas amphibian Xenopus Bf has been clearly identified as Bf. Thus the gene duplication and/or the subsequent structural and functional differentiation between the Bf and C2 genes seem to have occurred in the main line of jawed vertebrate evolution before the divergence of amphibians. However, all teleost Bf analyzed so far in medaka, zebrafish, carp, and trout show characteristics intermediate between mammalian Bf and C2, making a clear assignment of them to Bf or C2 impossible.