Evolution of the complement system: ancient molecules and new evidences from tunicates

The complement system is a key player in innate immunity but, recently, it is becoming even more evident that complement plays also important roles in adaptive immunity. Components of the human complement system possess unique domain structures and are classified in protein families: C3, factor B (Bf), mannan-binding protein-associated serine protease (MASP), C6 and factor I (If) family. These complement families probably derive from exon shuffling, which created the unique domain structures of each family, and gene duplication and subsequent functional divergence, which increased the number of members in each family. Accumulating information on the complement system of vertebrates indicates that these gene duplications, which played a pivotal role in establishing the classical and the lytic pathway, occurred in jawed vertebrates. In contrast, information on complement genes of invertebrate chordates is limited and, so far, only the ascidians, such as Ciona intestinalis and Halocinthia roretzi, and the cephalochordate Branchiostoma floridae have an almost complete set of the complement gene families: C3-, Bf-, MASP-, and C6-like genes. In the present work we demonstrate the presence of C6-, C3-, MASP-, MBL- and Bf-like genes in the colonial ascidian Botryllus schlosseri and the enhanced transcription after zymosan infection, which indicates their involvement in the ascidian immunity. The observation of a transcribed C6 gene suggest that the presence of the lytic pathway predates the appearance of the vertebrates. We are now carrying out new investigation to demonstrate a complement-related lytic activity in B. schlosseri