Conservation Pattern, Homology Modeling and Molecular Phylogenetic Study of BMP Ligands

Abstract

Background: Bone Morphogenic Proteins (BMPs) play many important roles in embryogenesis and metamorphosis throughout the life of vertebrates and other animals. The BMPs are multifunctional and some BMPs do similar functions which lead us to believe that it may have existed before the evolution and they may evolve from a single BMP. Additionally, less is known regarding phylogeny and conservation based conserved molecular mechanism of BMPs. Hence, evolutionary relationship of 16 BMP ligands (phylogenetic as well as protein sequence conversed patterns) were done. Materials and Methods: For this study, protein sequences were retrieved from UniProtKB, homology modeling was executed by Swiss-model using 3rjr.1A and 2qcq.1A as template, followed by MSA and phylogeny. Later conserved regions of BMP ligand were compared. Protein subfamily determination was done in Zebra and supported by the phylogenetic data. Results: Remarkably, similar region of conserved area were observed and different disulfide linkage pattern had been identified. It was found notable patterns in C1-C4, C2-C5 and C3-C6 that all but BMP3 and BMP15 do not contain 7th Cys. Phylogeny study indicate, according to evolutionary clock, GDF11 and BMP15 were more distantly diverged taxa, BMP3A and BMP3B had same point origin and GDF5, 6 and 7 are homologous. These seven proteins, as per this study indicates that, those are evolved at simultaneously during evolution, whereas other nine forms monophyletic taxa. Conclusion: However, more studies needs to explore on this. As per homology modelling studied, BMP ligands shares common evolutionary origin, some of the members are highly diverged indicating ancient evolutionary history of these protein. This study will be useful for wet lab once the evolutionary relationship gets established.