title: The ancient origin of the complement system.
abstract: The complement system has been thought to originate exclusively in the deuterostomes. Here, we show that the central complement components already existed in the primitive protostome lineage. A functional homolog of vertebrate complement 3, CrC3, has been isolated from a 'living fossil', the horseshoe crab (Carcinoscorpius rotundicauda). CrC3 resembles human C3 and shows closest homology to C3 sequences of lower deuterostomes. CrC3 and plasma lectins bind a wide range of microbes, forming the frontline innate immune defense system. Additionally, we identified CrC2/Bf, a homolog of vertebrate C2 and Bf that participates in C3 activation, and a C3 receptor-like sequence. Furthermore, complement-mediated phagocytosis of bacteria by the hemocytes of horseshoe crab was also observed. Thus, a primitive yet complex opsonic complement defense system is revealed in the horseshoe crab, a protostome species. Our findings demonstrate an ancient origin of the critical complement components and the opsonic defense mechanism in the Precambrian ancestor of bilateral animals.
authors.affiliation: Department of Biological Science, National University of Singapore, Singapore, Singapore.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Saravanan
authors.initials: S
authors.lastname: Thangamani
authors.forename: Bow
authors.initials: B
authors.lastname: Ho
authors.forename: Jeak Ling
authors.initials: JL
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003167:Complement Activation; D003165:Complement System Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006737:Horseshoe Crabs; D006868:Hydrolysis; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D003165:Complement System Proteins