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Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
Functional evolution of the microfibril-associated glycoproteins
1Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th St., Philadelphia, PA 19104, USA. segade@dental.upenn.edu
Abstract:
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.
Insights
Microfibril-associated glycoproteins (MAGPs) are crucial for elastic fiber structure. This study reveals MAGP1
Area of Science:
- Biochemistry
- Evolutionary Biology
- Molecular Biology
Background:
- Microfibril-associated glycoproteins (MAGPs) are essential components of the fibrillin-based microfibrillar complex.
- MAGPs play vital roles in microfibril and elastic fiber structure, homeostasis, and vascular development across vertebrates.
- The evolutionary history and conservation extent of MAGP1 and MAGP2 in vertebrates remain largely unknown.
Purpose of the Study:
- To investigate the evolutionary history and conservation of microfibril-associated glycoproteins (MAGPs) in vertebrates.
- To identify the earliest homologs of MAGP1 and MAGP2 across diverse vertebrate lineages.
- To elucidate the evolutionary trajectories and selective pressures acting on MAGP1 and MAGP2.
Main Methods:
- Sequence similarity searches were performed on nucleotide and protein databases to identify MAGP homologs.
- Phylogenetic and phylogenomic analyses were employed to reconstruct evolutionary relationships and assess synteny conservation.
- Functional divergence estimates and nucleotide substitution models were used to analyze selective constraints.
Main Results:
- MAGP1 homologs were identified in monotremes, birds, elasmobranchs, and agnathans, indicating an ancient origin.
- MAGP2 homologs were found in marsupials, birds, and teleosts, suggesting evolution from a gene duplication event.
- MAGP2 exhibits rapid evolution in bony vertebrates, potentially driven by relaxed selective constraints and correlated evolution with Notch1, while MAGP1 remained under strong purifying selection.
Conclusions:
- MAGP1 and MAGP2 have distinct evolutionary histories, with MAGP1 being ancient and MAGP2 evolving later within vertebrates.
- The rapid evolution of MAGP2 in bony vertebrates represents a significant innovation, influenced by interactions with developmental regulators.
- Understanding the evolutionary dynamics of MAGPs provides insights into the structural integrity and development of elastic fibers.
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