Environment-specific effects of new mutations on gene expression

新突变对基因表达的环境特异性影响

• 批准号: 8909817
• 负责人: Andrea Hodgins-Davis
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8909817
• 关键词: Affect; Antibiotic Resistance; Bacterial Antibiotic Resistance; Basic Science; Biological Assay; Cells; DNA mapping; Data; Development; Environment; Evolution; Exhibits; Flow Cytometry; Gene Expression; Genes; Genetic; Genotype; Growth; Health; Human; Individual; Link; Logic; Malignant Neoplasms; Maps; Measures; Mutate; Mutation; Natural Selections; Neoplasm Metastasis; Nucleic Acid Regulatory Sequences; Nucleotides; Phenotype; Population; Process; Property; Reporter Genes; Role; Saccharomyces cerevisiae; Saccharomycetales; Sampling; Shapes; Signal Transduction; Site-Directed Mutagenesis; Translating; Variant; Yeasts; collaborative environment; experience; fitness; gene environment interaction; genetic variant; high throughput screening; insight; novel; pathogen; promoter; public health relevance; trait

 DESCRIPTION (provided by applicant): Variation in the environment in which genotypes are translated into phenotypes can both induce phenotypic differences through plasticity and filter phenotypic variation for different optima via natural selection. Understanding the evolution of plasticity thus requires disentangling the role of environment as an agent of development and as an agent of selection, possible only through studying the phenotypic effects of new mutations not yet subject to selection. Here I propose to investigate the effects of new mutations on gene expression levels across environmental contexts in budding yeast. Taking advantage of a high throughput screen for isolating new mutations influencing gene expression, I will characterize the distribution of mutational effects on gene expression and the degree of correlation among the effects of individual new mutations across environments for nine genes. Through site-directed mutagenesis, I will investigate the effects of cis regulatory mutations on gene expression to identify the breadth of expression changes possible across environments through disruption of known regulatory motifs, and measure their consequences for growth. By examining the effects of these new regulatory mutations on fitness, I will characterize the evolutionary signal for selection on plasticity in gene expression.