Evolution of the albumin: α-fetoprotein ancestral gene from the amplification of a 27 nucleotide sequence

The genes for α-fetoprotein and albumin arose by duplication of an ancestral gene that contained three genetic domains. These domains were generated by the triplication of a primordial genetic domain composed of five exons or subdomains. That the primordial domain itself arose by amplification of a simpler sequence is suggested by nucleotide sequence homologies among the subdomains of the mouse α-fetroprotein gene. A detailed analysis of these homologies reveals that each of the five subdomain families contains remnants of a 27-base-long repeat from which the entire α-fetoprotein coding sequence has been assembled. A consensus sequence for the 27 nucleotide repeat is derived, and the positions of the repeats within each subdomain are described. A model is proposed for the evolution of the primordial domain by the amplification and divergence of the 27 base-pair sequence, along with the condensation of the repeats into subdomains separated by intervening sequences. It is postulated that the role of intervening sequences may be to limit sequence amplification in genes such as a-fetoprotein and albumin whose protein products cannot tolerate size variation.