Fibrinogen alpha genes: conservation of bipartite transcripts and carboxy-terminal-extended alpha subunits in vertebrates.

All three well-studied subunits of the clotting protein fibrinogen (alpha, beta, gamma) share N-terminal structural homologies, but until recently only the beta and gamma chains were recognized as having similar globular C-termini. With the discovery of an extra exon in the human fibrinogen alpha gene (exon VI), a minor form of the alpha subunit (alpha E) with an extended beta- and gamma-like C-terminus has been identified (Fu et al., Biochemistry 31, 11968, 1992). In the present study, the polymerase chain reaction has been used to identify sequences that encode counterparts to alpha E in chicken, rabbit, rat, and baboon. The basic six-exon structure of the fibrinogen alpha genes is shown to be conserved among mammals and birds, as are the intron positions. Bipartite transcripts--still bearing an intron prior to the last exon--are found among the products of the various vertebrate fibrinogen alpha genes. The last exon represents the largest conserved segment of the gene and, in each species examined, encodes exactly 236 amino acids. The C-termini of these alpha E chains align without a single gap and are between 76 and 99% identical. Since the exon VI-encoded domain of alpha E is as well conserved as the corresponding regions of the beta and gamma chains, it follows that it is equally important and that alpha E-fibrinogen plays a vital, if as-yet unrecognized physiological role.