Structure and evolutionary origin of the gene encoding a human serum mannose-binding protein

Area of Science:

• Molecular Biology
• Genetics
• Immunology

Background:

• The major human serum mannose-binding protein (MBP) plays a role in innate immunity.
• Understanding the genetic basis of MBP is crucial for elucidating its function and regulation.

Purpose of the Study:

• To determine the genomic structure of the human mannose-binding protein (MBP) gene.
• To investigate the evolutionary origins and regulatory mechanisms of human serum MBP.

Main Methods:

• cDNA sequencing and comparison with protein sequence.
• Oligonucleotide-directed cloning of the genomic DNA using cosmid libraries.
• Analysis of intron/exon structure and nucleotide sequences.
• Identification of consensus sequences in the promoter region.

Main Results:

• The N-terminal sequence of human MBP matched the predicted amino acid sequence from a cDNA clone.
• The human MBP gene's intron/exon structure closely resembles that of the rat MBP gene.
• Exon sequences showed variations compared to a previously published human cDNA clone.
• The MBP molecule's domains (signal peptide, cysteine-rich, collagen-like, neck, carbohydrate-binding) are each encoded by a separate exon.
• Consensus sequences in the promoter region suggest regulation as an acute-phase protein.

Conclusions:

• The exon-shuffling hypothesis for gene evolution is supported by the human MBP gene's structure.
• Human serum MBP is likely regulated as an acute-phase protein synthesized by the liver.