Functional evolution of the microfibril-associated glycoproteins

The microfibril-associated glycoproteins (MAGPs) are cysteine-rich low molecular weight components of the fibrillin-based microfibrillar complex. MAGPs are evolutionarily conserved in vertebrates and have important roles in microfibril and elastic fiber structure, homeostasis, and vascular development. Two MAGPs, designated MAGP1 and MAGP2, are encoded in the mammalian genome. Although MAGP sequences have been identified in several vertebrate species, the extent of conservation and evolutionary history of the MAGPs in vertebrates is unknown. Sequence similarity searches of nucleotide and protein databases identified the first homologs of MAGP1 in monotremes, birds, elasmobranchs and agnathans, and the first MAGP2 genes in marsupials, birds and teleosts. A model for MAGP evolution is presented. Phylogenetic analysis identified the ancient origin of MAGP1 and the evolution of MAGP2 from a gene duplication event early in vertebrate evolution. Phylogenomic analysis shows conservation of synteny between teleosts and tetrapods and suggests a multigene duplication event. The MAGP2 gene has evolved rapidly as an innovation in the bony vertebrate lineage. Estimates of functional divergence and complex nucleotide substitution models suggest that the divergence of MAGP2 took place by relaxation of selective constraints; and that MAGP1 has consistently been constrained by strong purifying selection. Correlated evolution between MAGP1 and the developmental regulator, Notch1, may explain some of the selective forces acting on MAGP2.