Collapsin Response Regulator Protein Family Of Adaptive Evolution And Positive Selection Analysis In The Nervous System

Objective:(1) Understand the orthologous and paralogous relationshipsbetween the CRMP family members, to trace the family evolutionary history;(2)detect the selection pressure of CRMPs in the process of biological evolution;(3)to investigate the relationship between positive selection sites and functionalsites and the possible roles in the pathogenesis of nervous system diseases.Methods: We have performed a comprehensive bioinformatics analysis ofCRMP gene family: first, sequence similarity searches have been performed ingenome data to identify homologues of CRMPs in vertebrates, phylogenetic treewere constructed by using the Bayesian method and maximum likelihoodmethod. To determine molecular substitution rates and the selective force ofCRMPs, we used several complementary methods, including site-specificmodels, branch-specific models and branch-site models. At last, it was therelationship between positive selection sites and functional area, and the analysisof putative biological significance.Results: In phylogenetic analysis, five CRMP members in vertebratesmight form through gene duplication. The inferred evolutionary transitions thatseparate members which belong to different gene clusters correlated withchanges in functional properties. In the process of estimating molecularsubstitution rates and determining the selective force operating at each CRMPsgene cluster,23positive selection sites and the functional areas were detected.Positive selected sites351F,305L,376D,430Y,483A,264E,324K and379Awere located in α-helix. Positively selection sites245S,376D and541S locatedin or near the area of the casein kinase II phosphorylation site;586K located intyrosine kinase phosphorylation site while607G in the domain ofN-myristoylation site. Conclusion: This research gives us a first look at the phylogeny andevolutionary selection pressure of the CRMP family in vertebrates. Additionally,we identified a number of critical amino acid residues likely relevant for thedistinct functional properties of the paralogues. This study reveals CRMPs’ rolesin the pathogenesis of nervous system diseases and provides a new thought ofthe targeted therapy from the molecular evolution angle.