title: Origin of structural domains of the serum-albumin gene family and a predicted structure of the gene for vitamin D-binding protein.
abstract: We have recently determined complete DNA sequences for the human albumin and alpha-fetoprotein [AFP] genes and thus have identified their detailed structures. Each is composed of three domains of four exons, three of which are internal and one of which is a domain-linking exon. Equivalent exons in each domain show sufficient sequence and structural similarity to be considered homologous; additional unique exons at each end of the gene show no similarity to the internal triplicated structures. Since earlier, conflicting evolutionary models were based on analysis of single gene structures, we derived from five genes a series of consensus sequences representing the three internal exons as well as the domain-linking exon. The five genes were human and rat albumin and human, mouse, and rat AFP genes. Structurally equivalent exons of the different domains are shown to have arisen from a single exon in a one-domain precursor. Exons that bridge the domains arose from an unequal crossover that fused two exons of the precursor. Our model suggests that part of the coding sequence of the one-domain precursor may have been derived from an intron, by way of loss of a splice site. The consensus sequences were used to propose an intron-exon structure for the related gene encoding the serum vitamin D-binding protein (DBP). DBP is truncated relative to albumin and AFP, and we submit that this results from deletion of two internal exons in the third domain of the gene rather than from premature termination of the coding sequence.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005091:Exons; D005796:Genes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D012709:Serum Albumin / Q000235:genetics*; D013045:Species Specificity; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D012709:Serum Albumin; D014809:Vitamin D-Binding Protein; D000509:alpha-Fetoproteins