本文選題：Collapsin + 反應(yīng)調(diào)節(jié)蛋白（CRMPs）　； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：(1)了解Collapsin反應(yīng)調(diào)節(jié)蛋白（Collapsin responsemediator proteins, CRMPs）家族內(nèi)基因成員的直系同源與旁系同源關(guān)系，追蹤C(jī)RMP家族的進(jìn)化歷史；(2)檢測(cè)CRMPs在生物進(jìn)化過程中受到的選擇壓力；(3)探討處于正選擇壓力下的位點(diǎn)與功能位點(diǎn)之間的關(guān)系及其可能在神經(jīng)系統(tǒng)疾病發(fā)病中的作用。 方法：本文對(duì)Collapsin反應(yīng)調(diào)節(jié)蛋白家族成員進(jìn)行了一系列的研究：首先根據(jù)序列相似性搜索的方法在基因組層面來(lái)鑒定脊椎動(dòng)物中CRMP的同源基因，，運(yùn)用貝葉斯法及最大似然法進(jìn)行系統(tǒng)進(jìn)化樹的構(gòu)建；其次，對(duì)每個(gè)CRMP基因簇采用了多重互補(bǔ)的方法估計(jì)分子替換速率和選擇壓力，包括：位點(diǎn)模型、枝模型以及枝位點(diǎn)模型；最后，將篩選出來(lái)的正選擇位點(diǎn)與功能位點(diǎn)之間的位置關(guān)系及可能帶來(lái)的生物學(xué)意義進(jìn)行分析。 結(jié)果：系統(tǒng)進(jìn)化分析發(fā)現(xiàn)脊椎動(dòng)物中5個(gè)CRMP家族成員可能來(lái)自于基因復(fù)制事件，不同的成員根據(jù)其同源性及功能特性在系統(tǒng)進(jìn)化樹上歸于不同的基因簇。為了了解脊椎動(dòng)物CRMPs在生物進(jìn)化過程中受到的選擇壓力，結(jié)果檢測(cè)出23個(gè)正選擇位點(diǎn)，正選擇位點(diǎn)351F、305L、376D、430Y、483A、264E、324K和379A正好落在α螺旋結(jié)構(gòu)區(qū)。有3個(gè)正選擇位點(diǎn)245S、376D及541S位于CK2激酶磷酸化位點(diǎn)附近區(qū)域；正選擇位點(diǎn)586K位于酪氨酸激酶磷酸化位點(diǎn)作用區(qū)域；而607G位于豆蔻�；揎椢稽c(diǎn)作用區(qū)域。 結(jié)論：本研究揭示了脊椎動(dòng)物中CRMP家族基因的系統(tǒng)發(fā)育以及進(jìn)化選擇壓力情況。另外，結(jié)果中發(fā)現(xiàn)了一系列關(guān)鍵的氨基酸殘基在同源蛋白質(zhì)中可能具有不同的功能。本文從分子進(jìn)化角度為研究CRMPs在神經(jīng)系統(tǒng)疾病發(fā)病中的作用及針對(duì)其的靶向治療提供了一個(gè)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 偽 -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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R741

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 劉燕燕;楊璇;韓松;蘇吉兒;羅宏;李俊發(fā);;cPKCγ參與低氧預(yù)適應(yīng)對(duì)小鼠腦缺血皮質(zhì)內(nèi)CRMP2水解和磷酸化的調(diào)節(jié)[J];基礎(chǔ)醫(yī)學(xué)與臨床;2012年01期

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