Tang Yanyan, Ye Ziming, Wei Yunfei, Lin Cuiting, Wang Yongbo, Qin Chao
Department of Neurology, First Affiliated Hospital, Guangxi Medical University, No. 22, Shuang Yong Road, 530021, Nanning, Guangxi, China.
J Mol Neurosci. 2015 Feb;55(2):324-34. doi: 10.1007/s12031-014-0327-2. Epub 2014 Jun 5.
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.
塌陷反应介导蛋白（CRMPs）家族主要在发育中的神经系统中表达，是塑造神经网络的关键分子成分。然而，关于CRMPs进化的了解有限。为了进一步深入了解脊椎动物神经系统的进化，我们对CRMPs进行了全面的生物信息学分析，包括系统发育分析、正选择位点及推定生物学意义的研究以及蛋白质结构分析。我们在基因组数据中进行了序列相似性搜索，以鉴定脊椎动物中CRMPs的同源物。构建了系统发育关系以追溯该家族的进化历史。五个CRMP成员可能通过基因复制形成。推断出的将属于不同基因簇的成员区分开的进化转变与功能特性的变化相关。为了确定脊椎动物中的进化模式，我们使用了几种互补方法，包括位点特异性模型、分支特异性模型和分支-位点模型来估计分子替代率，并确定作用于每个CRMPs基因簇的选择力。在此过程中检测到19个正选择位点和功能区域。这项研究让我们首次了解了脊椎动物中CRMP家族的系统发育和进化选择压力。此外，我们鉴定出了一些可能与旁系同源物独特功能特性相关的关键氨基酸残基。总之，本研究结果为CRMPs的分子进化提供了新的详细信息，揭示了CRMPs在神经系统疾病发病机制中的作用，并从分子进化角度为靶向治疗提供了新思路。
