Comparative Genomics of the Syndecans Defines an Ancestral Genomic Context Associated with Matrilins in Vertebrates

Background: The syndecans are the major family of transmembrane proteoglycans in animals and are known for multiple roles in cell interactions and growth factor signalling during development, inflammatory response, wound-repair and tumorigenesis. Although syndecans have been cloned from several invertebrate and vertebrate species, the extent of conservation of the family across the animal kingdom is unknown and there are gaps in our knowledge of chordate syndecans. Here, we develop a new level of knowledge for the whole syndecan family, by combining molecular phylogeny of syndecan protein sequences with analysis of the genomic contexts of syndecan genes in multiple vertebrate organisms.

Results: We identified syndecan-encoding sequences in representative Cnidaria and throughout the Bilateria. The C1 and C2 regions of the cytoplasmic domain are highly conserved throughout the animal kingdom. We identified in the variable region a universally-conserved leucine residue and a tyrosine residue that is conserved throughout the Bilateria. Of all the genomes examined, only tetrapod and fish genomes encode multiple syndecans. No syndecan-1 was identified in fish. The genomic context of each vertebrate syndecan gene is syntenic between human, mouse and chicken, and this conservation clearly extends to syndecan-2 and -3 in T. nigroviridis. In addition, tetrapod syndecans were found to be encoded from paralogous chromosomal regions that also contain the four members of the matrilin family. Whereas the matrilin-3 and syndecan-1 genes are adjacent in tetrapods, this chromosomal region appears to have undergone extensive lineage-specific rearrangements in fish.

Conclusion: Throughout the animal kingdom, syndecan extracellular domains have undergone rapid change and elements of the cytoplasmic domains have been very conserved. The four syndecan genes of vertebrates are syntenic across tetrapods, and synteny of the syndecan-2 and -3 genes is apparent between tetrapods and fish. In vertebrates, each of the four family members are encoded from paralogous genomic regions in which members of the matrilin family are also syntenic between tetrapods and fish. This genomic organization appears to have been set up after the divergence of urochordates (Ciona) and vertebrates. The syndecan-1 gene appears to have been lost relatively early in the fish lineage. These conclusions provide the basis for a new model of syndecan evolution in vertebrates and a new perspective for analyzing the roles of syndecans in cells and whole organisms.