Expansion of genes encoding complement components in bony fish: Biological implications of the complement diversity

The complement system is a major humoral component of vertebrate defenses for tagging and killing target microorganisms. Recent molecular analyses have uncovered a striking feature of bony fish complement, namely that several complement components are encoded by multiple genes. In this review, the structural diversity of C3, C4, C5, factor B, C2, C1r/s and MASP are discussed with special reference to their functional differentiation, mainly focusing on the common carp (Cyprinus carpio), a tetraploidized teleost. In carp, all the members (C3, C4, C5 and a non-complement protein α2-macroglobulin) of the thioester-containing protein family are present in multiple isotypes, differing in the primary structures of various functional sites. Three factor B/C2-like isotypes identified in carp showed distinct expression pattern (sites and inducibility), with one behaving as an acute-phase reactant. Two C1r/C1s/MASP2-like isotypes also contain an amino acid substitution that likely affects their substrate specificity. Overall, the present data suggest that the expanded genes of the carp complement system produce more diversified functional components than are known for mammals. The biological significance of this diversity is discussed.