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Development of "Molecular Structural Phylogeny" on the Consideration of Protein 3D structure

考虑蛋白质3D结构的“分子结构系统发育学”的发展

基本信息

批准号：
07304050
负责人：
TATENO Yoshio
金额：
$ 6.34万
依托单位：
National Institute of Genetics
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

With the advent of genome analysis, it has become clear that a gene is not a single entity but composed of subregions that have different evolutionary origins and histories. Consequently, it has been accepted that "one gene-multifunction, one gene-plural structures" is more realistic than "one gene-one function, one gene-one structure". This implies that a present gene has been formed by using smaller pieces in the course of the evolution. We call the piece the evolutionary motif (EM). To investigate the implication ;(1)We aligned complete amino acid sequences which were translated from DNA sequences in the International DNA Databases, in view of molecular evolution. To carry out the alignment, we developed a method by which to repeat phylogenetic tree construction and multiple alignment alternaively until both gave consistent results. Then we searched for EMs by locating evolutionarily conserved residues among the aligned sequences. The average length of the EMs was estimated to be 60 residues which is a size of many functional and structural regions in a protein.(2)EMs thus obtained were classified into hydrophilic, hydrophobic and intermediate ones. We think that hydrophilic EMs are located on the surface of a protein and play biological roles, and hydrophobic ones go inside it and something to do with its structure.(3)Analyzing the aligned sequences by estimating the numbers of synonymous and nonsynonymous substitutions, we came to the conclusion that the evolutionary mechanism for more than 90% of the total sequences could be explained by the neutral mutation theory.(4)We also elucidated three dimensional structures of cytochrome c oxidase and 3-isopropylmalate dehydrogenase, and confirmed that the structures were composed of substructures with different functions.The above findings strongly support our idea that a present gene was created and evolved by taking up (and throwing away) EMs that were available then.

随着基因组分析的出现，人们已经清楚地认识到基因不是一个单一的实体，而是由具有不同进化起源和历史的子区域组成的。因此，“一个基因-多功能，一个基因-多元结构”比“一个基因-一功能，一个基因-一结构”更为现实。这意味着现在的基因是在进化过程中使用更小的片段形成的。我们称其为进化基序（EM）。探究其含义；(1)从分子进化角度出发，对国际DNA数据库中翻译的完整氨基酸序列进行比对。为了进行比对，我们开发了一种重复系统发育树构建和多次比对交替进行的方法，直到两者得到一致的结果。然后，我们通过在排列序列中定位进化保守残基来搜索em。em的平均长度估计为60个残基，这是蛋白质中许多功能和结构区域的大小。(2)所得的emm分为亲水性、疏水性和中间型。我们认为亲水的电子元件位于蛋白质表面并发挥生物学作用，而疏水的电子元件则进入蛋白质内部并与蛋白质的结构有关。(3)通过估计同义和非同义替换的数量对比对序列进行分析，得出90%以上序列的进化机制可以用中性突变理论来解释。(4)我们还对细胞色素c氧化酶和3-异丙基苹果酸脱氢酶的三维结构进行了解析，并证实了它们是由不同功能的亚结构组成的。上述发现有力地支持了我们的观点，即现在的基因是通过吸收（和丢弃）当时可用的新兴基因而产生和进化的。