RESEARCH-PGR: A Genome-level Approach to Balancing the Vitamin Content of Maize Grain

该合作研究项目旨在确定玉米基因组中约40,000个基因中的一个子集，这些基因共同决定玉米粒中五种必需和限制性膳食维生素的水平：维生素E和四种B族维生素，B1（硫胺素），B2（核黄素），B3（烟酸）和B6（吡哆醇）。通过结合与人类基因组计划类似的方法，研究人员将识别等位基因，这些“维生素”基因的特殊变异，并学习如何将它们组合在一起，在玉米粒中产生大量的维生素。这项研究的一个重要成果将是提高玉米粒中这些微量营养素水平的知识，以便以玉米为主要成分的饮食提供均衡的营养成分。这种对这些发现的直接转化将最终在玉米育种计划中纳入和固定已确定的等位基因，这有利于提高维生素E和B的水平，从而改善食品和饲料供应链。此外，该研究将为其他农作物的类似研究提供指导原则，从而使全球更有营养的作物的预测育种和代谢工程成为可能。最后，将研究与教育结合起来，将有助于培养具有植物遗传学、育种、基因组学、生物化学和生物信息学知识的下一代植物科学家。该项目旨在利用过去十年在玉米领域开发的大量遗传和基因组工具集，推进和加速我们对控制维生素合成和积累的基因、等位基因和遗传机制的基本理解，这些基因、等位基因和遗传机制限制了玉米籽粒的合成和积累，从而导致以玉米为基础的饮食中维生素的缺乏：四种B族维生素（B1、硫胺素、B2、核黄素、B3、烟酸和维生素B）。该项目汇集了一组具有不同但互补的知识和技能的科学家，他们将共同阐明控制这些营养性状的基因、等位基因和潜在机制，并在全球范围内部署这些知识。具体目标是：(i)与玉米Ames自交系小组（n~ 2000）进行全基因组关联研究，以确定和解决控制这些微量营养素积累的数量性状位点（QTL）；（ii）通过构建和分析从性状极端异常的Ames系衍生的F2分离群体来评估稀有等位基因的作用；（iii）利用代表Ames面板表型变异的500个自交系授粉后24天谷物的全转录组测序数据，确定表达QTL和存在缺失变异（pav）对维生素组成的贡献；（iv）与Ames小组一起进行基因组预测，以加快发展中国家改良谷物微量营养素组成的育种效率。通过学生、博士后、科学家和公众参与的一系列协调活动，将确保该项目对更广泛的科学界和公众产生更广泛的影响。这个项目产生的数据和生物资源将向社会开放。数据将通过出版物、项目网站和长期存储库（如NCBI的SRA和MaizeGDB）传播。

This collaborative research project is directed at identifying a subset of the ~40,000 genes in the corn genome that work together to determine the levels of five essential and limiting dietary vitamins in kernels: vitamin E and the four B vitamins, B1 (thiamin), B2 (riboflavin), B3 (niacin) and B6 (pyridoxine). By combining approaches similar to those used in the Human Genome project, the researchers will identify alleles, special variations in these "vitamin" genes, and learn how to put them together to generate high amounts of vitamins in corn kernels. An important outcome of this research will be the knowledge by which to enhance these micronutrient levels in corn kernels such that diets in which maize is a major component provide a balanced nutritional content. Such direct translation of these findings will be the eventual incorporation and fixation of identified alleles in maize breeding programs that are favorable for the increased levels of vitamins E and B to enhance the food and feed supply chain. In addition, this research will provide guiding principles for parallel efforts in other agricultural crops and thus enable predictive breeding and metabolic engineering of more nutritious crops worldwide. Finally, integration of research with education within the project will permit training of the next generation of plant scientists with knowledge of plant genetics, breeding, genomics, biochemistry, and bioinformatics. This project seeks to leverage the tremendous genetic and genomic tool sets developed in maize the past decade to advance and accelerate our fundamental understanding of the genes, alleles and genetic mechanisms controlling synthesis and accumulation of vitamins that are limiting in maize grain and hence result in vitamin deficiencies in maize-based diets: four B vitamins (B1, thiamine; B2, riboflavin; B3, niacin; B6, pyridoxine) and vitamin E. This project brings together a team of scientists with divergent but complementary knowledge and skills that together will allow the genes, alleles and underlying mechanisms controlling these nutritional traits to be elucidated and the knowledge deployed on a global scale. Specific objectives are to (i) perform genome-wide association studies with the maize Ames inbred line panel (n~2,000) to identify and resolve quantitative trait loci (QTL) controlling accumulation of these micronutrients; (ii) assess the role of rare alleles by constructing and analyzing segregating F2 populations derived from Ames lines that are extreme outliers for traits; (iii) determine the contribution of expression QTL and presence-absence variants (PAVs) to vitamin composition using whole transcriptome sequencing data obtained from grain 24 days after pollination in 500 inbred lines that represents the phenotypic variation of the Ames panel; and, (iv) perform genomic prediction with the Ames panel to accelerate the efficiency of breeding improved grain micronutrient composition in developing countries. The broader impacts of this project to the broader scientific community and public will be ensured through a set of coordinated activities that engage students, postdoctoral associates, scientists and the public. Data and biological resources generated in this project will be made accessible to the community. Data will be disseminated through publications, project websites and long-term repositories such as the NCBI's SRA and MaizeGDB.