Characterization of murine mannose-binding protein genes Mbl1 and Mbl2 reveals features common to other collectin genes.
Mannose-binding protein (MBP) is a member of a family of collagenous lectins (collectins), which are believed to play an important role in first-line host defense. In this study, the two genes encoding MBP in mice--Mbl1 and Mbl2--have been isolated and their exon-intron structure studied to understand their evolutionary relationship to the single human (MBL) and the two rat MBP genes. Mouse Mbl1 and Mbl2 have five and six exons, respectively. The structure of the mouse Mbl genes is similar to that of the rat and human MBP genes and shows homology to the other collectin genes, with the entire carbohydrate recognition domain being encoded in a single exon and all introns being in phase 1. The MBP encoded by mouse Mbl1 with three cysteines in the first coding exon, like the rat Mbl1 and human MBL, is capable of a higher degree of multimerization and has apparent ability to fix complement in the absence of antibody or C1q. However, the structural features of other exons, that is, the larger size of collagen domain region in the first coding exon (64 bp in Mbl2 vs 46 bp in Mbl1) and the smaller size of the exon encoding the trimerization domain (69 bp in Mbl2 vs 75 bp in Mbl1) reveal that the single human MBL gene is closely related to rodent Mbl2 rather than rodent Mbl1. The findings in this study suggest that in contrast to the evolution of another collectin gene--bovine surfactant protein-D--which duplicated in bovidae after divergence from humans, MBP gene most likely duplicated prior to human-rodent divergence, and that the human homolog to Mbl1 was perhaps lost during evolution.
Sastry
R
R
Department of Pathology, Boston University School of Medicine, Massachusetts 02118, USA.
Wang
J S
JS
Brown
D C
DC
Ezekowitz
R A
RA
Tauber
A I
AI
Sastry
K N
KN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002417:Cattle; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005796:Genes; D006801:Humans; D007438:Introns / Q000235:genetics; D037102:Lectins / Q000235:genetics*; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives*; D037241:Mannose-Binding Lectins; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011110:Polymorphism, Genetic; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D002352:Carrier Proteins; D018076:DNA, Complementary; D037102:Lectins; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; C445639:Mbl2 protein, mouse; C445599:Mbl2 protein, rat; C069858:mannose binding protein A