From a jack-of-all-trades arise masters of few: uncovering the evolutionary patterns and processes driving multigene family functional diversification

从多才多艺的人中脱颖而出：揭示驱动多基因家族功能多样化的进化模式和过程

• 批准号: 2325341
• 负责人: Todd Barkman
• 金额: $ 50.14万
• 依托单位: Western Michigan University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2325341&HistoricalAwards=false
• 关键词: jack; trades; arise; masters; few

Specialized metabolites are not only the spice of life, they mediate nearly all organismal interactions with the environment. Due to their importance, this proposed work aims to understand how the 200,000 chemicals produced by plants and microorganisms evolved. Knowledge of the historical genetic mechanisms allowing for existing metabolites to be produced should allow for the generation of novel metabolites by protein engineering for applications in agriculture, medicine, bioengineering and pharmaceuticals. In order to achieve these research goals, the next generation of diverse scientists at different stages of development will be trained and collect data. At least 100 undergraduate students will be engaged in authentic research experiences that generate novel data so that their findings related to protein evolution and specialized metabolite biosynthesis can be published in peer-reviewed journals. This experience is expected to increase the probability of student recruitment into scientific research careers.The origins of genomic complexity are unclear but at least partly depend on gene duplication to generate multigene families. This project will investigate the factors that promote multigene family functional diversification after gene duplication, a topic of broad applicability to the thousands of enzymes involved in reactions required for life. To do this, the SABATH enzyme family of methyltransferases, which produce critical molecules for plant development and defense, will be studied. Ancestral Sequence Resurrection will be employed to directly study the ancestral enzymes that gave rise to modern-day enzymes. First, 10,000 enzyme assays will be performed to determine whether protein functional divergence is asymmetrical throughout enzyme family diversification by resurrecting ancient pre- and post-duplication enzymes. Second, the hypothesis that two descendant genes are better than one ancestral gene in terms of biochemical function will also be tested. To do this, the amount of biochemical products produced by pre- and post-duplication enzymes will be measured. Third, ancestral protein crystal structures will be generated for multiple ancestral and descendant enzymes in this family and analyzed in a comparative context to gain insight into active site configurations concomitant with evolutionary changes in enzyme substrate preferences.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.

专门的代谢物不仅是生活的香料，而且还介导了几乎所有与环境的有机体相互作用。由于其重要性，这项拟议的工作旨在了解植物和微生物产生的200,000种化学物质是如何发展的。 了解允许产生现有代谢产物的历史遗传机制的知识，应允许通过蛋白质工程为农业，医学，生物工程和药品的应用生成新型代谢产物。为了实现这些研究目标，将在不同发展阶段进行下一代不同的科学家进行培训和收集数据。至少有100名本科生将参与真正的研究经验，以产生新的数据，以便他们的发现与蛋白质进化和专业代谢物生物合成有关，可以发表在同行评审的期刊上。预计这种经验将增加学生招募科学研究职业的可能性。基因组复杂性的起源尚不清楚，但至少部分取决于基因重复来产生多基因家族。该项目将调查基因复制后促进多基因家族功能多样性的因素，这是对成千上万涉及生命反应的酶的广泛适用性的主题。为此，将研究为植物发育和防御产生关键分子的甲基转移酶家族。祖先序列复活将被用于直接研究产生现代酶的祖先酶。首先，将进行10,000种酶测定，以确定蛋白功能差异是否通过复活古老的前和杀伤后酶来不对称。其次，在生化功能方面，两个后代基因比一个祖先基因更好的假设也将被测试。为此，将测量由前后酶产生的生化产品的量。第三，将生成该家族中多种祖先和后代酶的祖先蛋白质晶体结构，并在比较环境中进行分析，以深入了解与酶底物偏好的进化变化有关的主动现场配置，这是NSF的法定任务，反映了由Infectirial构成的支持者，这一奖项已被认为是构成的依据。