Collaborative Research: GCR: Functional Epistasis - the Key for Understanding the Rules of Life

合作研究：GCR：功能上位——理解生命规则的关键

• 批准号: 1934860
• 负责人: Jeffrey Townsend
• 金额: $ 49.77万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1934860&HistoricalAwards=false
• 关键词: Collaborative; Research; GCR; Functional; Epistasis

This Growing Convergence Research project is seeking to explain the resilience of genotype-phenotype maps through functional epistasis via a convergence of three overlapping fields of investigation: molecular evolution, data science and statistical physics. The project is motivated by an unanticipated amount of variation in populations, gene families, and phylogenetic groups revealed by DNA sequencing of genes, individuals, and species. These voluminous data on variation are posing unexpected challenges to the (nearly) neutral theory of molecular evolution that explains the fate of new mutations in a population through random genetic drift and purifying selection. The research team will employ mechanistic models of epistasis, co-evolutionary processes, and deep learning. Deep integration across disciplines will be key for exploring the pivotal role of epistasis and, ultimately, for interrogating the most fundamental rules of life. The research team proposes a transdisciplinary project to set the foundations for a novel neutral-by-epistasis theory of molecular evolution. This team hypothesizes that a vast majority of population variation and species differences are due to random genetic drift of mutations that are neutral by epistasis, even though each may be individually detrimental. The new neutral-by-epistasis theory unites both neutral and nearly-neutral theories of molecular evolution and has the potential for a paradigm shift in which epistatic interactions between positions, rather than any individual position are the primary unit of comparative analysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个不断增长的收集研究项目正在旨在通过功能性上位症来解释基因型 - 表型图的韧性，这是通过三个重叠的研究领域的收敛性来解释：分子进化，数据科学和统计物理学。 该项目是由人群，基因家族和系统发育群体的意外变异所激发的，这些群体由基因，个体和物种的DNA测序揭示。 这些关于变异的大量数据对（几乎）中性的分子进化理论提出了意外的挑战，该理论通过随机的遗传漂移和净化选择来解释种群中新突变的命运。 研究团队将采用上毒，共同进化过程和深度学习的机械模型。 跨学科的深层整合将是探索上思议的关键作用的关键，最终是审问最基本的生活规则。研究小组提出了一个跨学科项目，以为新型的逐个疾病的分子进化理论设定基础。 该团队假设绝大多数种群变异和物种差异是由于关重的突变的随机遗传漂移引起的，即使每个人都可以单独有害。 新的中性逐个疾病理论将分子进化的中性和几乎中立理论融合在一起，并具有范式转变的潜力，在该理论中，在职位之间的同上相互作用，而不是任何个人立场是比较分析的主要单位。该奖项反映了NSF的法定任务，并通过评估基金会的范围来反映了基金会的范围，并已被评估了基金会的范围。