大肠杆菌细胞对环境的适应分化分子机制

生物进化是生命体对环境的适应分化结果，而适应分化的根本是基因突变。然而，基因突变如何使生命适应环境，其分子机制是什么等问题仍有待于解决。为回答这些问题，从大肠杆菌（Escherichia coli）原代单细胞开始，在三种温度各培养30个细胞群2000代后，得到3x30个2000-代细胞群；用基因组重测序技术，已确定了3x30个2000-代细胞的基因组突变谱。在此基础上，本项目用RNA-seq技术，将确立3x30个细胞群2000-代细胞转录组变化谱，建立基因组突变谱与转录组变化谱的联系；分析其环境适应表型，建立转录组变化谱与环境适应的联系；筛选出与适应分化有关关键基因并验证其在细胞环境适应中的作用。本研究将从分子生物学视角，用基因组学和转录组学大数据，结合遗传学表型，揭示细菌细胞对环境的适应分化分子机制。对揭示生命环境适应和进化规律具有理论意义，对细菌耐药性研究也有借鉴和指导作用。

Evolution is the result of environmentally adaptive differentiation of living organisms and gene mutations are the root of such adaptive differentiation. However, how the gene mutations result in environmentally adaptive differentiation of living organisms and the molecular mechanism of the adaptation have been remained unknown. To answer the questions, 30 populations under each selection of three various temperatures starting from a single cell of Escherichia coli (ancestor cell) were propagated for 2000 generations, obtaining 3x30 populations of 2000-generation cells. The genomes of the resultant 3x30 populations (2000-generation cells) were re-sequenced and genomic mutation pattern for each population was subsequently constructed. Based on the results obtained, the study has been designed: (i) to analyze global transcription pattern in each of 3x30 2000-generation cells and then establish the correlation of pattern in global transcription change with the genomic mutation pattern for each population; (ii) to build connection between adaptive phenome and global transcription pattern in each population through measuring the adaptive phenotype; (iii) also to test the roles of key genes screened from results obtained in cell adaptation. The study attempts to show molecular mechanisms for environmentally adaptive differentiation of E. coli cells through setting up correlations of transcription patterns with genome mutations and of adaptive phenotype with changes in transcriptome, using large data of genome-wide mutations and transcriptome from an angle of molecular biology in the methods of experimental evolution and genetic phenotype analysis. The study will shed light on molecular mechanisms of environmental adaptation and of bacterial antibiotic resistance.