Evolution of the complement components with unique domain structure

To elucidate the evolutionary origin and history of the blood complement system, comprehensive cloning of the five complement gene families, the complement component 3 (C3), factor B (fB), mannan-binding protein-associated serine protease (MASP), complement component 6 (C6), and factor I (fI) families, was performed in agnathan lamprey and cnidarian sea anemone. In additions, for the C6 family which was not found in these animals, chondrichthyes shark was analyzed by RT-PCR using the consensus-degenerate hybrid oligonucleotide primers. The draft genome search and RACE analysis using cnidarian, Nematostella vectensis resulted in identification of the C3, fB and MASP genes. These genes were completely absent in the draft genome sequences of placozoa, porifera, and choanofllagelata, indicating that the multi-component complement system was established in the early stage of eumetazoan evolution before the divergence of Cnidaria and Bilateria. In situ hybridization showed the endoderm-specific expression of the identified cnidarian complement genes, indicating that the cnidarian complement system acts mainly in the primitive gut cavity called coelenteron, the only cavity facing endoderm. On the other hand, the liver EST analysis of lamprey, Lethenteron japonicum, gave the genes for the C3, fB, MASP, and fI families. However, no evidence for the gene duplication/functional divergence within these families, which was essential for establishing the classical activation pathway of the mammalian complement system, was obtained. RT-PCR analysis using the universal primers for the C6 family genes identified one C6 gene from shark but none from lamprey, indicating that the unique domain structure of C6 family was established in a common ancestor of the jawed vertebrate.These results suggest that the complement system comprising at least three components, C3, fB, and MASP, was established in the common ancestor of eumetazoan animals more than 600 million years ago. Function of the primitive complement system was most probably the protection of the gut cavity with primitive circulatory function. Remaining two families, the fI and C6 families, appeared in the primitive vertebrates, before the divergence of cyclostomes for the fI family (more than 500 million years ago), and before the divergence of the Chondrichthyes for the C6 family (more than 400 million years ago), respectively. The gene duplication/functional divergence within each complement gene family, which played essential roles in establishing the sophisticated complement system of jawed vertebrates, was occurred immediately after appearance of all the five complement gene families in the common ancestor of the jawed vertebrates報告番号: 甲24505 ; 学位授与年月日: 2009-03-23 ; 学位の種別: 課程博士 ; 学位の種類: 博士(理学) ; 学位記番号: 博理第5403号 ; 研究科・専攻: 理学系研究科生物科学専