Complete structural organization of the human alpha 1 (V) collagen gene (COL5A1): divergence from the conserved organization of other characterized fibrillar collagen genes.

Genes that encode the vertebrate fibrillar collagen types I-III have previously been shown to share a highly conserved intron/exon organization, thought to reflect common ancestry and evolutionary pressures at the protein level. We report here the complete intron/exon organization of COL5A1, the human gene that encodes the alpha 1 chain of fibrillar collagen type V. The structure of COL5A1 is shown to be considerably diverged from the conserved structure of the genes for fibrillar collagen types I-III. COL5A1 has 66 exons, which is greater than the number of exons found in the genes for collagen types I-III. The increased number of exons is partly due to the increased size of the pro-alpha 1(V) N-propeptide, relative to the sizes of the N-propeptides of the types I-III procollagen molecules. In addition, however, the increased number of exons is due to differences in the intron/exon organization of the triple-helix coding region of COL5A1 compared to the organization of the triple-helix coding regions of the genes for collagen types I-III. Of particular interest is the increase of 54 bp exons in this region of COL5A1, strongly supporting the proposal that the triple-helix coding regions of fibrillar collagen genes evolved from duplication of a 54 bp primordial genetic element. Moreover, comparison of the structure of COL5A1 to the highly conserved structure of the genes of collagen types I-III provides insights into the probable structure of the ancestral gene that gave rise to what appears to be two classes of vertebrate fibrillar collagen genes.