The Evolution of Complement System Functions and Pathways in Vertebrates

An evolutionarily ancestral complement system is considered to be an opsonic system that seems to be a combination of the lectin and alternative pathways known in mammalian complement. The ancestral system is equipped with lectin-like pattern-recognition molecules linked with specific proteases homologous to the mannose-binding lectin-associated serine protease (MASP) and factor B, which cleave C3 into physiologically active forms with inflammatory and opsonic functions, as seen in primitive invertebrate species. In vertebrates, two rounds of whole-genome duplication allowed the occurrence of two additional reaction cascades, the classical and lytic pathways, providing jawed vertebrates with much more specific and efficient ability of pathogen elimination. A trace of molecular and functional evidence that represents a transient status from invertebrate prototypic complement to a full equipped system can be found in extant jawless species such as lamprey. A striking diversity of complement component isoforms unique to teleost fish is also discussed in evolutionary and functional points of view.