Structure of the gorilla alpha-fetoprotein gene and the divergence of primates.

The sequence of the gorilla alpha-fetoprotein gene, including 869 base pairs of the 5' flanking region and 4892 base pairs of the 3' flanking region (24,607 in total), was determined from two overlapping lambda phage clones. The sequence extends 18,846 base pairs from the Cap site to the polyadenylation site, and it reveals that the gene is composed of 15 exons, which are symmetrically placed within three domains of alpha-fetoprotein. The deduced polypeptide chain is composed of a 19-amino-acid leader peptide, followed by 590 amino acids of the mature protein. The RNA polymerase II binding site, TATAAAA, and the promoter element, CCAAC, are positioned at -21 and -65 from the Cap site, respectively. The polyadenylation signal, AATAAA, is located in the last exon, which is untranslated. The sequence for the gorilla alpha-fetoprotein gene was compared with that of the previously published human alpha-fetoprotein gene (P. E. M. Gibbs, R. Zielinski, C. Boyd, and A. Dugaiczyk, 1987, Biochemistry 26: 1332-1343). Four types of repetitive sequence elements were found in identical positions in both species. However, one Alu and one Xba DNA repeat within introns 4 and 7, respectively, of the human gene are absent from orthologous positions in the gorilla. The Alu and the Xba DNA repeats probably emerged in the human genome after the human/gorilla divergence and became established novelties in the human lineage. There are 363/21,523 mutational changes between human and gorilla, amounting to 1.69% DNA divergence between the two primate species. The value of 1.69% is lower than the 2.27% obtained from melting temperatures of hybrids between human and gorilla genomic DNA (C. G. Sibley and J. E. Ahlquist, 1984, J. Mol. Evol. 26: 99-121). At the protein level, Homo sapiens differs from Gorilla gorilla only at 4 of 609 amino acid positions (0.66%) in the alpha-fetoprotein sequence. This difference signifies a lower rate of molecular divergence for the alpha-fetoprotein gene in primates, as compared to rodents.