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几类特殊进化地位原生生物 SMC 及其复合成分的分析鉴定与SMC 的起源进化研究
其他题名Identification of SMC and other Complex Subunits in Several Protists with Unique Evolutionary Status and the Origin and Evolution of SMC Family
张国莉
学位类型博士
导师文建凡
2006
学位授予单位中国科学院研究生院
学位授予地点北京
关键词原生生物 Smc 克隆表达 Mukb 起源进化
摘要真核细胞有丝分裂过程中染色体的动态变化是细胞生物学研究的基本问题 之一。虽然人们早就观察到了有丝分裂过程中染色体的这种变化,但对其中所涉 及到的蛋白及机制问题只是在近二十年来才陆续有些研究。现已知SMC 家族蛋 白在染色体的组织、分离过程中扮演了至为关键的角色。但这类蛋白的进化研究 相对较少,尤其是在进化地位特殊的原生生物中的情况尚未有研究报道。本文对 SMC 及其复合体成分在几种原生生物中的存在情况进行了调查,进而对该蛋白 在整个原核生物和真核生物中的起源和演化问题进行了探讨。 通过基因组搜索等生物信息学手段,我们鉴定了四种原生生物中的全部的 SMC 同源序列,并对这些序列进行了分析。结果显示除贾第虫缺少典型的SMC5, 锥虫中缺少SMC5、SMC6 的同源序列外,其它SMC 的同源序列均在这些生物 中找到。还发现毛滴虫中SMC 同源序列表现出明显的多拷贝现象,其编码序列 (ORF)具有明显的核苷酸A 偏好性。对这些蛋白进行的二级结构预测显示出 一些与高等真核生物有所不同的特征,尤其是贾第虫中的SMC 蛋白更表现了独 特的二级结构特征。这些特点可能与这些生物核分裂过程中某些独特的染色体动 态变化特征相关联。对与SMC 形成复合体的蛋白在这些生物中的存在情况也做 了调查,发现它们在这些生物中只有小部分存在。这表明由SMC 组成的 “SMC/Kleisin/non-SMC﹠Kleisin”复合体在这几种生物可能较为简单或者在非 SMC 亚基方面有较大的分化。 为了进一步研究与形成典型中期染色体密切相关的两种蛋白SMC2 和 TopoII 在未发现凝聚染色体的贾第虫中的功能,本文还对贾第虫的这两个基因进 行了原核表达载体的克隆构建和表达。成功构建了重组质粒,并在相应的菌种中 得到了大量的包涵体表达。经过纯化进行兔子免疫制备出了抗血清,为后续研究 这两种蛋白在贾第虫细胞周期中的定位分布和贾第虫的核分裂打下了基础。 最后,我们对SMC 及同功蛋白MukB 在原核中的存在情况以及它们与真核 生物SMC 的分子系统关系进行了系统研究。发现MukB 及其组成的复合体仅存 在于γ 蛋白菌中的 Enterobacteriale、Pasteurellaceae 和Vibrionaceae 中,且在物 种间非常保守,应是较晚时期进化形成的;衣原体类、α蛋白菌中的立克次氏体、 ε 蛋白菌中没有任何SMC 或MukB 同源序列,也没有与其形成复合体的蛋白。 II 由于这些原核生物均为高度寄生菌,推测应该是由于寄生完全丢失了这类蛋白, 而利用宿主的相应装置完成对自身基因的组织。分子系统分析的结果显示MukB 与SMC 距离较远,不是同源蛋白,应是趋同进化的结果。真核的SMC 与原细 菌SMC 距离最近,应有最近的共同祖先。
其他摘要Dynamic behaviour of chromosomes during mitosis process is one of the fundamental issues in cell biology. Although the dramatic structural changes of chromosome during the cell cycle were observed, until last two decades more work have got some results on proteins involved in the process and how do they function. It’s known that the SMC proteins play crucial roles in mitotic chromosome condensation, segregation, and DNA repair. But little work has been done on evolution of SMCs and it is little known that what case SMCs of protists having special evolution positon do. The thesis investigated the distribution of SMCs and their interactional proteins in several protists and analysed the origin and evolution of SMCs between prokaryote and eukaryote. In this thesis, we identified whole SMCs from 4 protists using genome blast and other bioinformatics methods. The results of analysing these seuqences showed that all SMC homologs were found in these species except for non SMC5 homlog in Giardia lamblia and non SMC5/SMC6 in Trypanosoma cruzi. In addtion, the results also showed that the multiple copy of SMC homologs in Trichomonas vaginalis and the code sequence (ORF) bias on A nuleotide. The results of coiled-coil prediction suggested that significant difference existed between the SMCs in protists and other eukaryotes. Especially the SMC2 and SMC4 of G. lamblia displayed unique chracteristics of secondary structure. The characteristics may associate with the unique chromosome dynamic changes during nuclear divission. We also investigated the proteins interacting with SMCs and the rusults showed only three of six proteins were found in these protists. The results suggested that the complex composed of “SMC/Kleisin/non SMC﹠Kleisin”became simple or have divergence largely in these protists. In order to studying in future the function of SMC2 and TopoII, two key factors involved in assembling the mitotic chromosome, in G. lamblia which was found no mitotic chromosome during mitosis, the thesis has done the work that cloning the segment of the two genes to prokaryotic expression vector and expressing in E. coli. We successfully cloned the two genes into expression vector pGEX-KG and over expressed the fusion proteins in right E. coli. We aquired abundant inclusion proteins and purified the inclusions. Then we used the inclusions immuned the habbit and prepared the anti-serum. Lastly, we studied the distribution of SMC and MukB in prokaryote and phylogenetic relationships with eukaryote. We found MukB/MukE/MukF exsiting only in three gama Proteobacteria, Enterobacteriales, Pasteurellaceae, Vibrionaceae and the identity between species is very high. This results suggested the complex may evolve recently. Non SMC or MukB were found in Chlamydiae, Rickettsiales, epsilon Proteobacteria, and non related proteins were found. These species all belonged to entirely parasitic bacteria. We supposed that the proteins may lose in these species for their parasitic life and the parasites could organize their genomes using the apparatus of hosts. The reconstructed phylogenetic trees suggested that MukB and SMC have large distance and might undergone convergent evolution. The SMCs of eukaryote and SMCs of Archea have more close relationships and might share more recent common ancestor.
语种中文
文献类型学位论文
条目标识符http://ir.kiz.ac.cn/handle/152453/6488
专题科研部门_真核细胞进化基因组(文建凡)
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张国莉. 几类特殊进化地位原生生物 SMC 及其复合成分的分析鉴定与SMC 的起源进化研究[D]. 北京. 中国科学院研究生院,2006.
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