Partial mRNA sequences for human A alpha, B beta, and gamma fibrinogen chains: evolutionary and functional implications.

Abstract

Using rat cDNA [complementary DNA] and genomic probes to screen a human liver cDNA library, clones of 2274, 855 and 736 base pairs (bp) coding for the A.alpha., B.beta. and .gamma. chains of human fibrinogen were isolated. Sequence analysis reveals of hitherto unrecognized extension of 15 amino acids at the carboxyl terminus of the A.alpha. chain, the terminal residue of which is proline. This brings the known length of the human A.alpha. chain to 625 amino acids. The 13-amino-acid repeated region in the midportion of the A.alpha. chain clearly has arisen through an 8-fold duplication of a 39-bp genetic element, which itself appears to have been constructed from smaller 6-Bp repeating units. Greater than 50% sequence homology between B.beta.- and .gamma.-chain coding regions confirms postulates that these genes have arisen by duplication and subsequent divergence of an ancestral gene. A comparison of human and rat .gamma.-chain cDNA shows more than 88% sequence homology over the carboxyl-terminal 162 amino acids, implying strong selective pressures on these portions of the .gamma.-chain gene.