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DNAの進化と変異の機構

DNA进化和突变的机制

基本信息

批准号：
07454208
负责人：
HARADA Tomoko
金额：
$ 4.67万
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 (B)
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

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07454208/
关键词：
DNA polymorphism Molecular evolution Slightly deleterious mutation Adaptive evolution

项目摘要

Molecular mechanism of gene evolution has been a fundamental problem in evolutionary biology for many years. One focus of controversy concerns the effect and significance of natural selection. The present study mainly put a focus on dissection of DNA changes into nonsynonymous and synonymous substitutions which occurred among closely related species in mammals and Drosophila. Amino-acid-altering substitution, or nonsynonymous substitution, is naturally considered to be more exposed to natural selection than synonymous change. Thus, the comparison between these two patterens in a gene provides a good opportunity to evaluate the effect of natural selection. Along this line, we studied the pattern of molecular evolution in mammalian and Drosophila genes. Particularly, we could reveal that the ratio of replacement to synonymous changes in the lineage leading to rodent is lower than that in the primate lineage. This is consistent with the nearly neutral mutation model, which advocates that most of amino acid changes are slightly deleterious. The variation in nonsynonymous substitution among lineages was significant in mammals after weighting the lineage effects. The ratio of replacement to synonymous substitutions also varied significantly among lineages for some of the genes studied in Drosophila. This episodic molecular evolution cannot be explained by the epistatic effect among amino acid sites. Thus, fluctuation of population size or selective constraint should be taken into consideration. Otherwise, positive Darwinian evolution may have some impact on molecular evolution. Further study on higher-order interaction will be also needed to understand the molecular evolution of the complicated genetic systems and to dissect the effects of natural selection and random genetic drift.

基因进化的分子机制一直是进化生物学研究的一个基本问题。争论的焦点之一是自然选择的作用和意义。本研究主要集中在解剖DNA变化的非同义和同义的替代之间发生的密切相关的物种在哺乳动物和果蝇。氨基酸改变取代，或非同义取代，自然被认为是更容易受到自然选择比同义变化。因此，比较基因中的这两种模式为评估自然选择的效果提供了一个很好的机会。沿着这条路线，我们研究了哺乳动物和果蝇基因的分子进化模式。特别地，我们可以揭示，在导致啮齿动物的谱系中替换与同义变化的比率低于灵长类谱系。这与近中性突变模型一致，该模型主张大多数氨基酸变化是轻微有害的。在加权谱系效应后，哺乳动物谱系间的非同义替换差异显著。替代同义替换的比例也有显着不同的血统在果蝇中研究的一些基因。这种阶段性的分子进化不能用氨基酸位点间的上位效应来解释。因此，应考虑种群规模的波动或选择性约束。另外，积极的达尔文进化论可能对分子进化产生一些影响。为了理解复杂遗传系统的分子进化，剖析自然选择和随机遗传漂变的影响，还需要进一步研究高阶相互作用。