Collapsin反应调节蛋白家族在神经系统中的适应性进化与正选择位点分析

发布时间：2018-07-06 20:04

本文选题：Collapsin + 反应调节蛋白（CRMPs）　；参考：《广西医科大学》2014年硕士论文

【摘要】：目的：(1)了解Collapsin反应调节蛋白（Collapsin responsemediator proteins, CRMPs）家族内基因成员的直系同源与旁系同源关系，追踪CRMP家族的进化历史；(2)检测CRMPs在生物进化过程中受到的选择压力；(3)探讨处于正选择压力下的位点与功能位点之间的关系及其可能在神经系统疾病发病中的作用。方法：本文对Collapsin反应调节蛋白家族成员进行了一系列的研究：首先根据序列相似性搜索的方法在基因组层面来鉴定脊椎动物中CRMP的同源基因，，运用贝叶斯法及最大似然法进行系统进化树的构建；其次，对每个CRMP基因簇采用了多重互补的方法估计分子替换速率和选择压力，包括：位点模型、枝模型以及枝位点模型；最后，将筛选出来的正选择位点与功能位点之间的位置关系及可能带来的生物学意义进行分析。结果：系统进化分析发现脊椎动物中5个CRMP家族成员可能来自于基因复制事件，不同的成员根据其同源性及功能特性在系统进化树上归于不同的基因簇。为了了解脊椎动物CRMPs在生物进化过程中受到的选择压力，结果检测出23个正选择位点，正选择位点351F、305L、376D、430Y、483A、264E、324K和379A正好落在α螺旋结构区。有3个正选择位点245S、376D及541S位于CK2激酶磷酸化位点附近区域；正选择位点586K位于酪氨酸激酶磷酸化位点作用区域；而607G位于豆蔻酰化修饰位点作用区域。结论：本研究揭示了脊椎动物中CRMP家族基因的系统发育以及进化选择压力情况。另外，结果中发现了一系列关键的氨基酸残基在同源蛋白质中可能具有不同的功能。本文从分子进化角度为研究CRMPs在神经系统疾病发病中的作用及针对其的靶向治疗提供了一个新思路。
[Abstract]:Objective: (1) to study the lineal and collateral homology of the gene members of the Collapsin responsemediator proteins (CRMPs) family, and to trace the evolutionary history of the CRMP family, (2) to detect the selection pressure of the CRMPs during the biological evolution. (3) to explore the relationship between sites under positive selection pressure and functional loci and their role in the pathogenesis of nervous system diseases. Methods: a series of studies were carried out on the members of the Collapsin response regulatory protein family. Firstly, the homologous genes of CRMP in vertebrates were identified at the genomic level by the method of sequence similarity search. Bayesian method and maximum likelihood method are used to construct phylogenetic tree. Secondly, multiple complementary methods are used to estimate molecular substitution rate and selection pressure for each CRMP gene cluster, including: site model, branch model and branch site model. Finally, the location relationship between the positive selection site and the functional site and the possible biological significance are analyzed. Results: phylogenetic analysis revealed that five CRMP family members in vertebrates may come from gene replication events, and different members belong to different gene clusters in phylogenetic tree according to their homology and functional characteristics. In order to understand the selection pressure of vertebrate CRMPs in the course of biological evolution, 23 positive selection sites were detected, and the positive selection sites (351FU 305L ~ 376D) 430Y ~ (483A) ~ 264E ~ (324K) and 379A were located in the 伪 -helical structure region. Three positive sites 245Sn376D and 541S were located near CK2 kinase phosphorylation site, 586 K site was located at tyrosine kinase phosphorylation site, and 607G site was located at nutmeg site. Conclusion: this study revealed the phylogenetic and evolutionary stress of CRMP family genes in vertebrates. In addition, a series of key amino acid residues may have different functions in homologous proteins. This paper provides a new idea for studying the role of CRMPs in the pathogenesis of nervous system diseases and its targeted therapy from the viewpoint of molecular evolution.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R741

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