J. Biol. Chem., Vol. 261, Issue 14, 6398-6407, 05, 1986
Evolution of the apolipoproteins. Structure of the rat apo-A-IV gene and its relationship to the human genes for apo-A-I, C-III, and E
MS Boguski, EH Birkenmeier, NA Elshourbagy, JM Taylor and JI Gordon
We have determined the nucleotide sequence of the rat apolipoprotein (apo-)
A-IV gene and analyzed its structural and evolutionary relationships to the
human apolipoprotein A-I, E, and C-III genes. The rat A-IV gene is 2.4
kilobases in size and consists of three exons (142, 126, and 1157 base
pairs) interrupted by two introns (277 and 673 base pairs). The
5'-nontranslated region and most of the signal peptide are encoded by the
first exon. Thus, the apo-A-IV gene lacks an intron in the 5'-nontranslated
region of its mRNA in contrast to all other known apolipoprotein genes.
Sequences coding for amphipathic docosapeptides span both the second and
third exons of the rat A-IV gene. We demonstrate that this is also true for
the human apolipoprotein genes. This gene family seems to have evolved by
the duplication of an ancestral minigene that resulted in the formation of
two exons. Thereafter, evolution of these sequences was dominated by
intraexonic amplification of repeating units coding for amphipathic
peptides. Sequence divergence of these repeats resulted in the functional
differentiation of the apolipoproteins. However, conservation of the
fundamental amphipathic pattern allowed members of this protein family to
retain their lipid-binding properties.