WHALE HAGEMAN-FACTOR (FACTOR-XII) - PREVENTED PRODUCTION DUE TO PSEUDOGENE CONVERSION

In Southern blot analysis of the Hind III-digested whale genomic DNA o btained from the livers of two individual whales, we detected a single band with a size of five kilobase pairs which hybridized to full leng th guinea pig Hageman factor cDNA. We amplified two successive segment s of the whale Hageman factor gene by polymerase chain reaction (PCR), and sequenced the PCR products with a combined total of 1367 base pai rs. Although all of the exon-intron assemblies predicted were identica l to those of the human Hageman factor gene, there were two nonsense m utations making stop codons and a single nucleotide insertion causing a reading frame shift. We could not detect any message of the Hageman factor gene expression by northern blot analysis or by reverse transcr iption-polymerase chain reaction (ET-PCR) analysis. These results sugg est that in the whale, production of the Hageman factor protein is pre vented due to conversion of its gene to a pseudogene. The deduced amin o acid sequence of whale Hageman factor showed the highest homology wi th the bovine molecule among the land mammals analyzed so far. (C) 199 8 Elsevier Science Ltd.