Structure of a full-length cDNA clone for the preproα2(I) chain of human type I procollagen. Comparison with the chicken gene confirms unusual patterns of gene conservation

A cDNA clone from a human placental library was found to consist of an essentially full-length cDNA of 4.6 kb for the preproα2(I) chain of type I procollagen. Nucleotide sequencing of the 5'-end of the cDNA provided a sequence of 1617 nucleotide residues and codons for 539 amino acid residues not previously defined. Comparison of the complete structure of the preproα2(I) cDNA with previously reported sequences for the chicken proα2(I) gene indicated that 83% of 1366 total amino acid residues were conserved. In the α-chain domain 84% of 1014 amino acid residues were conserved. Also, there was conservation of the previously noted preference for U and C in the third position of codons for glycine, proline and alanine. One major difference between the human and the chicken preproα2(I) chain was that the human chain contained 21 fewer proline residues, an observation that probably explains why the triple helix of human type I procollagen unfolds at temperatures that are 1-2°C lower. In parallel experiments, sequencing of intron-exon boundaries for nine exons of genomic subclones confirmed and extended previous observations that the proα2(I) gene, like other genes from fibrillar collagens, has an unusual 54-base pattern of exon sizes that is highly conserved through evolution.