DISSERTATION RESEARCH: The fitness landscape of a yeast tRNA gene
论文研究:酵母 tRNA 基因的适应性景观
基本信息
- 批准号:1501788
- 负责人:
- 金额:$ 1.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-04-01 至 2017-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Mutation provides the raw material for all genetic variation and evolution. How those mutations affect the fitness of an individual and the distribution of those fitness effects, known as the fitness landscape, is of fundamental importance for understanding almost all evolutionary processes. This project will explore the fitness landscapes of a yeast gene. The data will offer unprecedented details of the fitness effects of mutations, including properties of genetic interaction among mutations, and provide an invaluable opportunity to test many theoretical models. These models are applied to many important phenomena such as the basis of genetic diseases, the origins of multidrug resistance in pathogens, and the domestication of animals and plants. This research explores the fitness landscape of the tRNA-ARG gene in the yeast Saccharomyces cerevisiae and studies epistasis between point mutations in the gene. The study will generate approximately 100,000 yeast strains, each carrying, at its native genomic location, a variant of the tRNA gene that has on average two single nucleotide changes compared to the wild-type. The fitness values of approximately 20,000 genotypes will be measured en masse by a sensitive high-throughput method, and epistasis will be estimated for a large number of mutation pairs. This study offers a rare opportunity to understand the biophysical basis of epistasis and fitness effects of mutations, because tRNA function is largely determined by its secondary structure, which can be computationally predicted with high accuracy. Further, fitness landscapes and epistasis will be quantified under multiple conditions to understand genotype by environment interactions. In addition, the expressions of different tRNA variants will be probed to better understand how the internal promoter of the tRNA works and how fitness is affected by the expression level of the tRNA.
突变为所有遗传变异和进化提供了原材料。这些突变如何影响个体的适应性以及这些适应性效应的分布,被称为适应性景观,对于理解几乎所有的进化过程都具有根本的重要性。这个项目将探索酵母基因的适应性景观。这些数据将提供突变的适应性效应的前所未有的细节,包括突变之间的遗传相互作用的特性,并为测试许多理论模型提供了宝贵的机会。这些模型被应用于许多重要的现象,如遗传疾病的基础,病原体的多药耐药性的起源,以及动物和植物的驯化。 本研究探讨了tRNA-ARG基因在酵母酿酒酵母中的适应性景观,并研究了该基因点突变之间的上位性。该研究将产生大约10万株酵母菌株,每株酵母菌株在其天然基因组位置携带tRNA基因的变体,与野生型相比,该变体平均具有两个单核苷酸变化。将通过灵敏的高通量方法连续测量约20,000个基因型的适应度值,并估计大量突变对的上位性。这项研究提供了一个难得的机会来了解上位性的生物物理基础和突变的适应性效应,因为tRNA的功能在很大程度上是由其二级结构决定的,这可以通过计算高精度地预测。此外,适应度景观和上位性将在多种条件下量化,以了解基因型与环境的相互作用。此外,不同的tRNA变体的表达将被探测,以更好地了解tRNA的内部启动子如何工作,以及适合度如何受到tRNA表达水平的影响。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jianzhi Zhang其他文献
Positive Selection on Genes in Humans as Compared to Chimpanzees
与黑猩猩相比,人类基因的正向选择
- DOI:
10.1002/9780470015902.a0020856 - 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
M. Bakewell;Jianzhi Zhang - 通讯作者:
Jianzhi Zhang
Accelerated evolution and loss of a domain of the sperm-egg-binding protein SED1 in ancestral primates.
祖先灵长类动物精卵结合蛋白 SED1 结构域的加速进化和丧失。
- DOI:
10.1093/molbev/msl066 - 发表时间:
2006 - 期刊:
- 影响因子:10.7
- 作者:
O. Podlaha;David M. Webb;Jianzhi Zhang - 通讯作者:
Jianzhi Zhang
No support for the adaptive hypothesis of lagging-strand encoding in bacterial genomes
不支持细菌基因组中滞后链编码的适应性假设
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Haoxuan Liu;Jianzhi Zhang - 通讯作者:
Jianzhi Zhang
Automation in synthetic biology using biological foundries
使用生物铸造厂实现合成生物学自动化
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Jianzhi Zhang;Tong Si;Jiandong Huang;Chenfei Ma;Zining Wang;Lihao Fu;Zhiyu Zhang;Zhenkun Zhang;Ting Tang;Erpeng Guo - 通讯作者:
Erpeng Guo
Hydrogen plasma reduction of iron oxides
氢气等离子体还原氧化铁
- DOI:
10.1016/j.ijhydene.2025.01.322 - 发表时间:
2025-03-04 - 期刊:
- 影响因子:8.300
- 作者:
Jianzhi Zhang;Zhiwei Peng;Tong Zhang;Wanlong Fan;Guanwen Luo - 通讯作者:
Guanwen Luo
Jianzhi Zhang的其他文献
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{{ truncateString('Jianzhi Zhang', 18)}}的其他基金
Yeast as a model for understanding heterosis
酵母作为理解杂种优势的模型
- 批准号:
1329578 - 财政年份:2013
- 资助金额:
$ 1.96万 - 项目类别:
Continuing Grant
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