Nucleotide sequence of the gene for human prothrombin

Area of Science:

• Genomics
• Molecular Biology
• Biochemistry

Background:

• Human prothrombin is a key protein in the blood coagulation cascade.
• Understanding the genetic structure of human prothrombin is crucial for insights into its function and regulation.

Purpose of the Study:

• To determine the complete DNA sequence of the human prothrombin gene.
• To analyze the structure, including exons and introns, and identify repetitive elements within the gene.
• To compare the intron characteristics with those of other vitamin K-dependent proteins and serine proteases.

Main Methods:

• Screening of a human genomic DNA library using a prothrombin cDNA probe.
• Characterization of positive lambda phage clones.
• DNA sequencing of the 21-kilobase human prothrombin gene.
• Analysis of exon-intron boundaries and repetitive DNA sequences.

Main Results:

• The human prothrombin gene comprises 14 exons and 13 introns, totaling 21 kilobases.
• Introns constitute 90% of the gene, with sizes ranging from 84 to 9447 base pairs.
• Thirty Alu and two KpnI repetitive DNA elements were identified within introns, accounting for 40% of the gene's sequence.
• Most intron splice junctions conform to eukaryotic gene standards, with one exception (GC instead of GT).

Conclusions:

• The human prothrombin gene exhibits a complex structure with extensive intron regions rich in repetitive DNA.
• The identified repetitive elements may play a role in gene regulation or evolution.
• Comparative analysis of intron size and distribution provides insights into the evolutionary relationships among serine proteases.