Vertebrate paralogous CRMPs in nervous system: evolutionary, structural, and functional interplay.

Collapsin response mediator proteins (CRMPs) family predominantly expressed in the developing nervous system as key molecular components in shaping neural networks. However, knowledge of the evolution of CRMPs is limited. To gain further insight into nervous system evolution in vertebrates, we have performed a comprehensive bioinformatics analysis of CRMPs, including phylogenetic analysis, an examination of positively selected sites and putative biological significance and protein structure analysis. Sequence similarity searches have been performed in genome data to identify homologues of CRMPs in vertebrates. Phylogenetic relationships were constructed to trace the family evolutionary history. Five CRMP members might form through gene duplication. The inferred evolutionary transitions that separate members which belong to different gene clusters correlated with changes in functional properties. To determine the mode of evolution in vertebrates, we used several complementary methods, including site-specific models, branch-specific models and branch-site models to estimated molecular substitution rates and determined the selective force operating at each CRMPs gene cluster. Nineteen positive selection sites and the functional areas were detected in this process. This research gives us a first look at the phylogeny and evolutionary selection pressure of the CRMP family in vertebrates. Additionally, we identified a number of critical amino acid residues likely relevant for the distinct functional properties of the paralogues. In conclusion, the results of this study contribute novel detailed information about the molecular evolution of CRMPs, reveal CRMPs' roles in the pathogenesis of nervous system diseases and provide a new thought of the targeted therapy from the molecular evolution angle.