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The Journal of Immunology, 2003, 170: 4701-4707.
Copyright © 2003 by The American Association of Immunologists

Origin of Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 and MASP-3 Involved in the Lectin Complement Pathway Traced Back to the Invertebrate, Amphioxus1,2

Yuichi Endo3,*, Masaru Nonaka{dagger}, Hidetoshi Saiga{ddagger}, Yuji Kakinuma*, Akiko Matsushita*, Minoru Takahashi*, Misao Matsushita* and Teizo Fujita*

* Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima, Japan; {dagger} Department of Biological Sciences, Graduate School of Science, University of Tokyo, and {ddagger} Department of Biological Sciences, Graduate School of Sciences, Tokyo Metropolitan University, Tokyo, Japan

Mannose-binding lectin-associated serine proteases (MASPs) are involved in complement activation through the lectin pathway. To elucidate the phylogenetic origin of MASP and a primordial complement system, we cloned two MASP cDNAs from amphioxus (Branchiostoma belcheri) of the cephalochordates, considered to be the closest relative of vertebrates. The two sequences, orthologues of mammalian MASP-1 and MASP-3, were produced by alternative processing of RNA from a single gene consisting of a common H chain-encoding region and two L chain-encoding regions, a structure which is similar to that of the human MASP1/3 gene. We also isolated two MASP genes from the ascidian Halocynthia roretzi (urochordates) and found that each of them consists simply of an H chain-encoding region and a single L chain-encoding region. The difference in structure between the ascidian MASP genes and the amphioxus/mammalian MASP genes suggests that a prototype gene was converted to the MASP1/3-type gene possessing two L chain-encoding regions at an early stage of evolution before the divergence of amphioxus. This conclusion is supported by the presence of MASP-1 and MASP-3 homologues in almost all vertebrates, as demonstrated by the cloning of novel cDNA sequences representing lamprey (cyclostomes) MASP-1 and Xenopus MASP-3. The ancient origin of MASP-1 and MASP-3 suggests that they have crucial functions common to all species which emerged after cephalochordates.




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