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A Genome-wide Analysis Of Transcriptional Noise In Pseudomonas Aeruginosa

Posted on:2022-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H ChenFull Text:PDF
GTID:1520306929992279Subject:Polymer Chemistry and Physics
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It’s common to think of an individual’s phenotype as the result of both their genotype and their environment.Nongenetic individuality,on the other hand,refers to the existence of individual differences among people who share the same genotype and environment.The nongenetic individuality often arises from stochastic fluctuations in the biochemical reactions of gene expression,or gene expression noise.There are two categories in which gene expression noise can have its roots.Gene-specific sources,such as promoter architecture and transcription factors,fall under one of the categories.The second category is the gene-independent source,which includes DNA topology,RNA polymerase numbers,and ribosome numbers.The most of genome-wide analysis of gene expression noise of prokaryotes was studied in Escherichia coli.These investigations shed light on the relationship between noise and gene function as well as how promoter regions of genes influence noise.Yet,there are large genetic variations among species,and our knowledge of other species is limited.In the paper,we focus on how the promoter regions of genes affect noise and the association between noise and genes’function in Pseudomonas aeruginosa by presenting a library of fluorescent transcriptional reporters over 90%of all promoters in P.aeruginosa and measuring the levels of expression and noise during the exponential growth phase and stationary growth phase at single-cell resolution.By analyzing our data,we discovered that expression noise strongly depends on expression levels.Expression noise is near to the gene-specific noise limit,which for low-expression-type promoters is inversely proportional to the mean.Expression noise approaches the overall noise limit and is unaffected by expression levels.We calculated the noise residuals,and and defines the noise residuals as noise of transcriptional regulation(NTR),in order to separate the impacts of changes in expression level on expression noise.This thesis identified 42 and 115 promoters with abnormally high NTR in exponential phase and stationary phase,respectively.We made the assumption that the increased noise of high-residual promoters results from noise propagation by comparing the variations in the noise of high-residual promoters.Additionally,we discovered positional impacts on noise,expression levels,and noise residuals.The interaction between gene function and expression noise was further investigated.During the stationary growth phase,there are increased amounts of noise and NTR in the genes encoding chemotaxis,motility,and secreted proteins.In the meantime,we discovered that virulence genes’ expression and noise both greatly increased.The analysis then focused on the correlation between the regulation of high NTR promoters and found a negative correlation between the regulation of the majority of high NTR promoters.Finally,we discovered that the values of noise residual increased with the fold change in expression levels.We also demonstrated that patterns corresponding with our empirical data are produced by a straightforward model linking single-cell expression levels,noise,and population fitness.
Keywords/Search Tags:nongenetic individuality, Pseudomonas aeruginosa, library of fluorescent transcriptional reporters, noise residual, fitness
PDF Full Text Request
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