FOR several decades it has been apparent that many diseases directly or indirectly involve collagen, the tough fibrous material that is the most abundant protein in the body and the major constitue...

Heritable Diseases of Collagen

The collagens represent an interesting example of a structurally related but genetically distinct family of proteins1. Type I, the most abundant of the vertebrate collagens, comprises two proα1(I) chains and one proα2(I) chain, each containing terminal propeptides and a central domain of 338 (Gly, X, Y) repeats. The structure of the chicken proα2(I) gene shows an intriguing relationship between exon organization and the arrangement of (Gly, X, Y) repeats (see ref. 2 for review). This has led to the suggestion3 that the collagens evolved from a common ancestral unit of 54 base pairs (bp). Here we present the structure of the entire human proα1(I) gene and compare this with the chicken proα2(I). The exon arrangement of the two genes is remarkably similar, although the human proα1(I) is more compact because of the shorter length of its introns. The data strongly support the notion that the type I genes have evolved from an ancestral multi-exon unit, and that once the gene was translated, a strong evolutionary pressure caused it to maintain this elaborate structure.

Human proα1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons

Publisher Summary This chapter emphasizes on new developments concerning the relatively well-characterized collagens as well as on studies describing the more recently discovered collagens. It is abundantly clear that although collagen molecules function primarily as components of supporting aggregates, they constitute a large family of proteins with a wide spectrum of chemical and structural features. The nature of the aggregates derived from various types of molecules reflects this diversity. The molecular diversity of the collagen family of proteins is, of course, specified ultimately by the various genes utilized in synthesizing different collagen chains. The genetic heterogeneity is, however, considerably amplified through intracellular posttranslational modifications of the nascent chains as well as through extracellular processing of secreted molecules. A number of factors have greatly facilitated the acquisition of data on most of the collagens described above. Use of limited proteolysis with pepsin to facilitate the release of fragments of the molecules is one of these factors. Fragmentation of the molecules constitutes a serious limitation when this approach is utilized. However, it appears likely that many of the collagens for which extensive data are now available would have remained undetected were it not possible to isolate their fragments by means of limited proteolysis.

The collagens: an overview and update.

Ascorbic Acid Specifically Increases Type I and Type III Procollagen Messenger RNA Levels in Human Skin Fibroblasts

cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain.

A recombinant plasmid containing sequences complementary to human pro-alpha l(I) collagen mRNA was used for the chromosomal assignment of the pro-alpha l(I) collagen gene. Restriction endonuclease analysis of DNA from mouse-human and Chinese hamster-human somatic cell hybrids revealed cosegregation with human chromosome 17. Hybrids containing derivative chromosomes with a t(2;17)(q14;q21) translocation showed cosegregation of the pro-alpha l(I) gene with the segment 17q21 leads to qter. In situ hybridization on human metaphasic chromosomes confirmed this conclusion.

https://www.pnas.org/content/pnas/79/21/6627.full.pdf

Human type I procollagen genes are located on different chromosomes.

A cDNA for the pro alpha 2 chain of human type I collagen has been recently cloned and amplified. We have used this specific probe to identify the human chromosome carrying the pro alpha 2(I) collagen gene. The DNA from 17 independent human/hamster and human/mouse somatic cell hybrids was digested by Eco RI and the restriction pattern analyzed in Southern blot experiments, using the 32P-labeled cDNA as a hybridization probe. The gene coding for the pro alpha 2 collagen subunit could be unambiguously assigned to human chromosome 7. All the other chromosomes, including chromosome 17, were excluded.

M S Gross

Papers

Human type I procollagen genes are located on different chromosomes.

Assignment of the human pro alpha 2(I) collagen structural gene (COLIA2) to chromosome 7 by molecular hybridization.

Workshop on mapping by somatic cell hybridization.