title: Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC.
abstract: To clarify the evolutionary origin of the linkage of the MHC class III complement genes with the MHC class I and II genes, we isolated C4 cDNA from the banded hound shark (Triakis scyllium). Upon phylogenetic tree analysis, shark C4 formed a well-supported cluster with C4 of higher vertebrates, indicating that the C3/C4 gene duplication predated the divergence of cartilaginous fish from the main line of vertebrate evolution. The deduced amino acid sequence predicted the typical C4 three-subunits chain structure, but without the histidine residue catalytic for the thioester bond, suggesting the human C4A-like specificity. The linkage analysis of the complement genes, one C4 and two factor B (Bf) genes, to the shark MHC was performed using 56 siblings from two typing panels of T. scyllium and Ginglymostoma cirratum. The C4 and one of two Bf genes showed a perfect cosegregation with the class I and II genes, whereas two recombinants were identified for the other Bf gene. These results indicate that the linkage between the complement C4 and Bf genes, as well as the linkage between these complement genes and the MHC class I and II genes were established before the emergence of cartilaginous fish >460 million years ago.
authors.affiliation: Department of Experimental Radiology, Shiga University of Medical Science, Ohtsu-shi, Shiga, Japan.
authors.forename: Tokio
authors.initials: T
authors.lastname: Terado
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Okamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Shin
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Smith
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Takemoto
authors.forename: Mayumi I
authors.initials: MI
authors.lastname: Nonaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Martin F
authors.initials: MF
authors.lastname: Flajnik
authors.forename: Masaru
authors.initials: M
authors.lastname: Nonaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular / Q000379:methods; D003167:Complement Activation / Q000235:genetics*; D003181:Complement C4 / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D011415:Complement Factor B / Q000235:genetics; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D008040:Genetic Linkage / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D012754:Sharks / Q000235:genetics* / Q000276:immunology*
chemical_list: D003181:Complement C4; D021122:Protein Subunits; D011415:Complement Factor B