Gene structure of chick cartilage chondroitin sulfate proteoglycan (aggrecan) core protein

Abstract

Large aggregating chondroitin sulfate proteoglycan (CSPG/aggrecan) is one of the major extracellular matrix components in cartilage. The core protein is also large, over 200 kDa, and modular with a distinct correspondence between protein structural domains and the encoding exons. Here we report the isolation, using chick CSPG cDNA probes and the ensuing sequencing, of genomic clones containing exons encoding the chick CSPG core protein. The 5′ two globular domains, G1 and G2, are encoded by four and three exons, respectively, and the interglobular domain is encoded by a single exon. The chondroitin sulfate attachment domain is encoded by the largest exon, 3,216 bp, which is approximately 50% of the total coding sequence. Combined with the previous report (Tanaka, T., Har-el, R. Tanzer, M.L. 1988 J. Biol. Chem. 263, 15831–15835), these data reveal that the chick CSPG gene contains at least 18 exons spanning a genome which is greater than 30 kb. No evidence was obtained for multiple genes for aggrecan in the chick genome. Elucidation of the chick genomic structure allows comparison of the avian and mammalian link protein genes to the homologous portions of avian and mammalian core protein genes (hyaluronate binding domain) with respect to their origins and paths of duplication and divergence.