环境胁迫诱导的细胞适应性突变  

Stress-induced cellular adaptive mutagenesis

作　　者：朱林江[1] 李崎[1] 

机构地区：[1]江南大学食品安全与营养协同创新中心,教育部工业生物技术重点实验室,无锡214122

出　　处：《遗传》2014年第4期327-335,共9页Hereditas（Beijing)

基　　金：2013基本科研-青年基金项目(编号:1012050205134030);中央高校基本科研业务费资金(编号:JUSRP51306A)资助

摘　　要：细胞具有普遍的突变和进化能力,如病原菌的抗药性、工业菌株的适应性和人体细胞的癌变等,但是细胞的适应性突变是如何产生的呢?通过非致死性突变分析模型的建立与应用,产生了新的适应性进化观点,即环境胁迫诱导细胞适应性突变。这种环境诱导的细胞突变过程涉及多方面的生理调控,包括细胞内毒性物质(如氧活性物质)积累并造成DNA损伤、DNA错配修复的活性受到抑制、胞内RpoS反应和SOS反应被激活等。这些反应使胞内高保真的DNA复制状态转变为低保真的DNA修复状态,提高胞内突变率和重组活性。此外,基因转录影响基因组的不稳定,容易产生DNA损伤,并造成局部的高突变率,即形成了转录偶联的DNA修复与突变为基础的适应性突变观点。文章围绕环境胁迫诱导细胞突变率增加和转录偶联的DNA修复与突变这两种适应性突变分子机制,阐述其相关的研究进展,以期更好地理解环境条件诱导细胞发生适应性突变的过程。The adaptive mutations exist widely in the evolution of cells,such as antibiotic resistance mutations of pathogenic bacteria,adaptive evolution of industrial strains,and cancerization of human somatic cells.However,how these adaptive mutations are generated is still controversial.Based on the mutational analysis models under the nonlethal selection conditions,stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint.The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses,including DNA damages caused by accumulation of intracellular toxic chemicals,limitation of DNA MMR （mismatch repair） activity,upregulation of general stress response and activation of SOS response.These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one.The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity.In addition,gene transcription under stress condition increases the instability of genome in response to DNA damage,resulting in transcription-associated DNA mutagenesis.In this review,we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

关 键 词：压力诱导突变 适应性进化 超突变态 转录偶联的DNA突变 

分 类 号：Q256[生物学—细胞生物学]