Ras 超家族蛋白的起源演化研究
文献类型：学位论文
| 作者 | 董玖红 |
| 学位类别 | 博士 |
| 答辩日期 | 2006-08 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 文建凡 |
| 关键词 | Ras 超家族蛋白 起源演化 原核生物 真核生物 |
| 其他题名 | The origin and evolution of the Ras superfamily proteins |
| 学位专业 | 动物学 |
| 中文摘要 | Ras超家族蛋白是真核生物中普遍存在的一类小分子GTP结合蛋白。它们具有高度保守的GTP结合结构域，根据序列结构和细胞功能被分为七个家族：Sar1、Arf、SRβ、Ran、Rab、Rho和Ras。这些蛋白分别行使着真核生物特有的细胞功能，诸如运输小泡的形成和转运（Sar1、Arf、Rab），胞质骨架的建成（Rho），细胞核-胞质运输及核膜重建（Ran）等，其起源演化和真核细胞的起源密切相关。本文利用生物信息学手段和分子生物学实验调查研究了原核生物和原生生物中Ras超家族蛋白同源物的存在情况，并进行了分子系统分析，对Ras超家族蛋白的起源演化问题进行了较为深入、系统的探讨。获得了以下结果和结论： 1）通过原核生物基因组的搜索和序列结构分析，在一些真细菌中首次鉴定出了高度相似于真核生物Ras超家族蛋白的原核生物同源物，且实验证明它们的基因具有表达活性；在原细菌中的产甲烷菌和热原体中也发现有序列分歧较大的同源物。并在更多的真细菌种类中鉴定出了更多的前人已报道的另一种小分子GTP结合蛋白—MglA。序列比对分析表明MglA蛋白具有自己独特的序列特征，与真核生物的Ras超家族蛋白序列差异较大。进一步的分子系统分析显示：真核生物Ras超家族蛋白的七个家族中，Ran、Rab、Rho和Ras等四个家族聚在一起，上述我们所鉴定的真细菌的Ras超家族蛋白同源物则紧聚在其外围；真核生物的另三个家族（Sar1、Arf、SRβ）聚成另一枝，并接着与产甲烷原细菌的的同源物及真细菌的MglA蛋白聚在一起。这些结果表明：Ras超家族蛋白不是前人所认为的为真核生物所特有，实际上在一些原核生物中就已产生；真核生物Ras超家族蛋白的祖先也不太可能是前人所认为的为真细菌的MglA；真核生物Ras超家族蛋白的七个家族可能有两种不同的起源：Ran、Rab、Rho和Ras等可能来源于蓝细菌或蛋白菌，或二者的共同祖先，而Sar1、Arf和SRβ可能来源于产甲烷原细菌，这也可能反映了真核细胞“融合起源”的历史。 2）通过搜索一些较为低等的单细胞真核生物——原生生物基因组中Ras超家族蛋白，并结合一系列其他处在不同进化地位真核生物的Ras超家族蛋白进行分析，发现Sar1、Arf、Rab和Ran家族的蛋白在真核生物中普遍存在，而SRβ、Rho和Ras家族蛋白在有些真核生物中未找到。根据各家族蛋白在真核生物中的分布情况推测在真核生物的最近共同祖先中存在的Ras超家族蛋白可能有下列两种情况：（1）最近的共同祖先已经具有了所有七个家族的蛋白，并且至少有11个成员：1个Sar1、1个SRβ、3个Arf（Arf1、Arl1、Arl2）、3个Rab（Rab1、Rab6、Rab11）、1个Ran、1个Rho（Rac）和1个Ras（RheB）。因而，部分真核生物中缺少SRβ、Rho和Ras家族蛋白很可能是因基因丢失所致。植物中Ras家族蛋白的缺少应该是由于在进化早期，其祖先绿藻丢失了单个Ras家族蛋白基因所致；（2）根据Cavalier-Smith的真核生物划分为单鞭毛（变形虫类、真菌和后生动物）和双鞭毛（藻类、植物和除变形虫外的原生动物）两大类的分类观点，真核生物最近的共同祖先可能只具有除Ras家族而外的六个家族的成员，而Ras家族蛋白则是在此两大类群分化以后在单鞭毛类生物中才产生的，多数双鞭毛类生物如原生动物、绿藻和植物中没有Ras的情况应该是一种祖征，而个别双鞭毛类生物如红藻具有的Ras家族蛋白则很可能是从单鞭毛类生物那里水平基因转移而来的。至于SRβ和Rho家族蛋白在部分物种中的缺少，则还是可能因为基因丢失所致。此外，变形虫类生物中大量的Ras超家族蛋白提示基因组的大小或进化地位的高低并不是Ras超家族蛋白成员多少的决定性因素，而细胞相应生理活动的需求才是家族成员增多的关键。 |
| 英文摘要 | Ras superfamily proteins are a group of ubiquitous small GTP binding proteins in eukaryotes. They share a high conserved GTP binding domain and have been classified into seven familes: Sar1, Arf, SRβ, Ran, Rab, Rho and Ras, based on their sequence characters and cellular functions. Each of these proteins performs specific cellular functions such as the vesicle trafficking (Sar1, Arf and Rab)，the cytoskeleton remodeling (Rho), the nucleocytoplasmic transport and the nuclear envelope remodeling (Ran) etc. The origin and evolution of the Ras superfamily proteins are closely related to the origin and evolution of the eukaryotes. By using the methods of bioinfamatics and through the experiments of molecular biology, the distribution of the Ras superfamily proteins in prokaryotes and protists were investigated, and further molecular phylogenetic analyses were performed. The origin and evolution of the Ras superfamily proteins were studied systematically and thoroughly. The results and conclusions are as follows: 1) Through searching the prokaryotic genomic databases and analyzing the sequence characters, the prokaryotic sequences showing high similarities to the eukaryotic Ras superfamily proteins were firstly identified in eubacteria，and the experiments indicated that the genes of them were actively transcribed. In Archaea, some sequences showing relatively high divergence from the eukaryotic Ras superfamily proteins were found in methanogenic ones and Thermoplasmales. The MglA proteins, which have been recognized as the prokaryotic small GTP binding proteins，were found in more eubacteria. Sequence alignment shows that MglA proteins have their own unique features very distinct from the eukaryotic Ras superfamily proteins. Further molecular phylogenetic analysis shows that among the seven families of the eukaryotic Ras superfamily proteins, four families (Ran, Rab, Rho and Ras) cluster together with the eubacterial ones showing high similarities to them closely branching outside of them; the other three families (Sar1, Arf and SRβ) form an another separate branch, clustering with the methanogenic archaebacterial homologues and eubacterial MglA proteins. These results suggests that the Ras superfamily proteins are not specific for eukaryotes, which indeed have originated in some prokaryotes; the ancestors of eukaryotic Ras superfamily proteins also should not be the eubacterial MglA as the people thoughted before; the seven families of eukaryotic Ras superfamily proteins may have two different origins: Ran, Rab, Rho and Ras evolve from Cyanobacteria, or alpha-proteobacteria, or the common ancestor of them, while Sar1, Arf, and Srbeta derive from methanogenic archaea, which may reflect the “fusion” evolutionary history of the eukaryotic cells. 2) Through searching the genomic databases of some relatively low unicellular eukaryotes, protists, and performing systematically analyses by combining the search results with the Ras superfamily proteins in a series of other eukaryotes in different evolutionary status, the Sar1, Arf, Rab and Ran were found to be ubiquitous in eukaryotes, while SRβ, Rho and Ras were not found in some eukaryotes. Based on the distribution conditions of each family members in eukaryotes, it is proposed that the composition of Ras superfamily proteins in the last common ancestor of eukaryotes may have two conditions: (1) the last common ancestor of eukaryotes have had all seven families mermers, and at least have eleven members: 1 Sar1, 1 SRβ，3 Arf (Arf1, Arl1, Arl2), 3 Rab (Rab1, Rab6, Rab11), 1 Ran, 1 Rho (Rac), 1 Ras (RheB). Therefore, the lack of SRβ, Rho and Ras families members in some eukaryotes probably is due to the gene losses. The absence of Ras family members in plants should be attributed to the loss of single Ras family protein gene in their ancestor of green algae; (2) based on Cavalier-Smith’ s classification of the euakryotes, in which the eukaryotes are classified into two big clades (the unikonts (Amoebazoa, fungi and metazoa) and bikonts (algaes, plants and the protozoa except Amoebazoa)), the last common ancestor of eukaryotes may only have the six family members except the Ras family, and the Ras family membes may derive in unikonts after the two big groups have diverged. The lack of Ras family members in green algae, plants and some protozoa may be an ancestral character. And the Ras family members in some bikonts such as the red algae may have been obtained through the lateral gene transfer from the unikonts. As for the absence of SRβ and Rho, it still may be due to the gene loss. In addition, the very large Ras superfamily proteins in Amoebazoa organisms suggested that the genome size and the evolutionary status are not the deciding factor of the small or large of the Ras superfamily proteins, and the corresponding requirements of cellular physiologic activies are indeed the key reason of the family members increasing. |
| 语种 | 中文 |
| 公开日期 | 2010-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6148]  |
| 专题 | 昆明动物研究所_真核细胞进化基因组 |
| 推荐引用方式 GB/T 7714 | 董玖红. Ras 超家族蛋白的起源演化研究[D]. 北京. 中国科学院研究生院. 2006. |
入库方式： OAI收割
来源：昆明动物研究所
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