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: 9461346
• 负责人: Andrea Hodgins-Davis
• 金额: $ 0.03万
• 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/9461346
• 关键词: Affect; Alpha Cell; 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; Interruption; 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; Work; Yeasts; exhaustion; 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.

 描述(由申请人提供)：将基因类型转化为表型的环境变化既可以通过可塑性引起表型差异，也可以通过自然选择过滤不同最佳表型的表型差异。因此，理解可塑性的进化需要理清环境作为发育因素和选择因素的作用，只有通过研究尚未进行选择的新突变的表型效应才能做到这一点。在这里，我建议研究新突变对萌芽酵母中不同环境背景下基因表达水平的影响。利用高通量筛选分离影响基因表达的新突变，我将表征突变对基因表达的影响的分布，以及跨环境对9个基因的单个新突变的影响之间的关联程度。通过定点突变，我将调查顺式调控突变对基因表达的影响，以确定通过破坏已知调控基序而在不同环境中可能发生的表达变化的广度，并衡量它们对生长的影响。通过研究这些新的调节突变对适合度的影响，我将描述选择的进化信号对基因表达可塑性的影响。