Investigating mechanisms of de novo gene birth in Saccharomyces cerevisiae

研究酿酒酵母基因从头诞生的机制

• 批准号: 10000118
• 负责人: S. Branden Van Oss
• 金额: $ 6.53万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000118
• 关键词: Address; Affect; Antifungal Agents; Area; Bioinformatics; Biological Models; Birth; Cell physiology; Cells; Cellular biology; Cloning; Cognition; DNA sequencing; Data; Data Set; Disease; Environment; Event; Evolution; Gene Expression; Genes; Genetic; Genetic Transcription; Genetic Variation; Genome; Goals; Human; Knowledge; Lead; Libraries; Life; Malignant Neoplasms; Mass Spectrum Analysis; Medical; Metabolic; Methionine; Methods; Modeling; Molecular; Mutation; Nature; Open Reading Frames; Orphan; Oxidative Stress; Pathway interactions; Peptides; Physiological; Play; Process; Proteome; RNA analysis; Regulation; Role; Saccharomyces cerevisiae; Saccharomycetales; Stress; Structure; System; Technology; Transcriptional Regulation; Translating; Translations; Untranslated RNA; Western Blotting; Yeasts; biological adaptation to stress; fitness; genetic element; genome-wide; high throughput screening; in silico; in vivo; innovation; insight; mRNA Expression; novel; overexpression; predictive modeling; promoter; ribosome profiling; screening; trait; transcription factor; transcriptome sequencing

Project Summary/Abstract Genetic diversity amongst species is due in part to the de novo emergence of new genes from noncoding regions of the genome. New genes that have emerged de novo have been found in every species thus far examined, including hundreds that have been identified in humans, and many disease-associated mutations are found in human-specific genes. “Proto-genes,” which display features intermediate between genic and non-genic sequences, may represent the pool from which de novo gene birth takes place, but very little is known about the extent, regulation, and physiological consequences of proto-gene expression. The goal of this proposal is to explore proto-gene expression in the budding yeast Saccharomyces cerevisiae through an integration of in silico and in vivo approaches. Proto-gene transcription will be assessed through a re-analysis of RNA-sequencing datasets, which will lead to predictions about the factors that govern proto-gene expression. Proto-gene translation will also be examined by both a re-analysis of mass spectrometry datasets and by high-throughput cloning followed by western blotting, and the structural features of proto-gene translation products will be examined computationally. Finally, by screening a proto-gene overexpression library for effects on fitness under various stress conditions, the adaptive potential of proto- gene expression will be examined. The studies proposed here will enhance our understanding both of the mechanisms that underpin de novo gene birth as well as the cellular function(s) of these proto-genes. !

项目总结/摘要 物种之间的遗传多样性部分是由于新基因的从头出现， 基因组的非编码区。新的基因已经从头出现， 到目前为止所研究的每一个物种，包括在人类身上发现的数百个物种， 在人类特异性基因中发现了许多与疾病相关的突变。“原始基因” 显示介于基因序列和非基因序列之间的特征，可以代表库 从那里开始基因的新生，但对它的程度知之甚少， 原基因表达的调节和生理后果。这个目标 研究目的是探索原基因在芽殖酵母酿酒酵母中的表达 通过计算机模拟和体内方法的整合。原基因转录将是 通过重新分析RNA测序数据集进行评估，这将导致预测 关于控制原始基因表达的因素原基因翻译也将是 通过对质谱数据集的重新分析和高通量 蛋白质印迹法克隆，原基因翻译的结构特征 产品将通过计算进行检验。最后，通过筛选原基因过表达， 库的影响健身在各种压力条件下，适应潜力的原， 将检测基因表达。这里提出的研究将提高我们的认识 这两种机制，支持从头基因诞生以及细胞功能（S）的 这些原始基因 !