Unraveling the genetic basis of amino acid composition in dry Arabidopsis seeds

揭示干燥拟南芥种子氨基酸组成的遗传基础

• 批准号: 1754201
• 负责人: Ruthie Angelovici
• 金额: $ 82.78万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754201&HistoricalAwards=false
• 关键词: Unraveling; genetic; basis; amino; acid

Essential amino acids are necessary for human health but must come from dietary sources, as the human body cannot produce them. A lack of these essential amino acids in a diet leads to malnutrition. Much of the world's human and livestock populations rely on seeds for protein, but most staple crops seeds are deficient in several essential amino acids. Efforts to fortify the amino acid composition of staple crop seeds have had limited success since plants respond to induced protein composition alterations by activating a regulatory mechanism that "resets" it back to an original state. While beneficial to the plant growth and development, this mechanism has been a major hurdle to biofortification efforts. Fortunately, it is also known that different cultivars/varieties display natural variation in their seed amino acid composition, which means that the regulation of these compounds is genetically driven and thus should be amenable to manipulation. Therefore, this project aims to identify the key genes involved in this regulatory mechanism by analyzing hundreds of Arabidopsis strains, which display natural genetic and seed amino acid composition variation. Subsequently the potential role of the identified candidate genes will be tested using classical physiological and genetic approaches. Identifying new genetics targets will help facilitate the breeding of new crop varieties that can support our nation's and world's growing population.It is important to identify the genes that underlie the amino acid composition of dry seeds. Doing so will shed new light on a complex regulatory mechanism in plants as well as facilitate efforts to fortify staple seed crops. While much is known about amino acid metabolic pathways, little is known about their regulation, especially in seeds. So far, it is known that alterations to the composition of seed storage proteins (i.e., the major amino acid sink) lead to proteomic reprogramming and activation of a rebalancing mechanism, a response that suggests tight regulation of this trait. Seed amino acid composition varies substantially across genotypes within the same genus. This observation implies that the genetic architecture responsible for this natural variation includes, at least in part, the genes involved in responding to amino acid sink alteration and activation of the rebalancing mechanism. This project aims to elucidate key components of this genetic architecture in Arabidopsis thaliana using two approaches: (1) a GWAS on amino acid composition measured from dry seeds of an 800-accession association panel and (2) an amino acid/gene expression correlation-based network analysis of wildtype and two storage protein mutants with active rebalancing phenotypes. The candidate genes identified from each approach will be compared, and the top candidate genes will be tested for involvement in amino acid regulation via knockdown and overexpression experiments. The identified genetic regulators will provide new targets for breeding programs.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.

必需氨基酸对于人类健康是必需的，但必须来自饮食来源，因为人体无法产生它们。饮食中缺乏这些必需氨基酸会导致营养不良。世界上许多人类和牲畜依靠种子获取蛋白质，但大多数主要农作物种子都缺乏几种必需氨基酸。强化主要作物种子氨基酸组成的努力取得了有限的成功，因为植物通过激活调节机制将其“重置”回原始状态来对诱导的蛋白质组成变化做出反应。虽然有利于植物的生长和发育，但这种机制一直是生物强化工作的主要障碍。幸运的是，众所周知，不同的品种/品种在其种子氨基酸组成中表现出自然差异，这意味着这些化合物的调节是由遗传驱动的，因此应该易于操纵。因此，该项目旨在通过分析数百个拟南芥菌株来鉴定参与该调节机制的关键基因，这些菌株显示出天然遗传和种子氨基酸组成的变化。 随后，将使用经典的生理学和遗传学方法测试已确定的候选基因的潜在作用。确定新的遗传学目标将有助于促进新作物品种的育种，从而支持我们国家和世界不断增长的人口。确定干种子氨基酸组成的基因非常重要。这样做将为植物复杂的调控机制提供新的线索，并促进强化主要种子作物的努力。虽然人们对氨基酸代谢途径了解甚多，但对其调节却知之甚少，尤其是在种子中。到目前为止，已知种子储存蛋白（即主要氨基酸库）组成的改变会导致蛋白质组重编程和重新平衡机制的激活，这种反应表明对该性状的严格调控。同一属内不同基因型的种子氨基酸组成差异很大。这一观察结果表明，造成这种自然变异的遗传结构至少部分包括参与响应氨基酸库改变和再平衡机制激活的基因。该项目旨在使用两种方法阐明拟南芥遗传结构的关键组成部分：(1) 对 800 个种质关联小组的干种子测量的氨基酸组成进行 GWAS 分析，以及 (2) 氨基酸/基因表达相关性基于野生型和具有主动再平衡表型的两种储存蛋白突变体的网络分析。将比较从每种方法中识别出的候选基因，并通过敲低和过表达实验来测试最重要的候选基因是否参与氨基酸调节。 确定的遗传调节因子将为育种计划提供新的目标。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

mGWAS Uncovers Gln-Glucosinolate Seed-Specific Interaction and its Role in Metabolic Homeostasis

mGWAS 揭示了 Gln-芥子油苷种子特异性相互作用及其在代谢稳态中的作用

• DOI: 10.1104/pp.20.00039
• 发表时间: 2020-04
• 期刊: Plant Physiology
• 影响因子: 7.4
• 作者: Slaten, Marianne L.;Yobi, Abou;Bagaza, Clement;Chan, Yen On;Shrestha, Vivek;Holden, Samuel;Katz, Ella;Kanstrup, Christa;Lipka, Alexander E.;Kliebenstein, Daniel J.;et al
• 通讯作者: et al

Genetic variation, environment and demography intersect to shape Arabidopsis defense metabolite variation across Europe

遗传变异、环境和人口统计交叉影响了整个欧洲拟南芥防御代谢的变异

• 发表时间: 2021-05
• 期刊: eLife
• 影响因子: 7.7
• 作者: Katz, E.;Li jj;Jaegle, B.;Ashkenazy, H.;Abrahams SR.;Bagaza C.;Holden S.;Pires CJ.;Angelovici R.;Kliebenstein DJ.
• 通讯作者: Kliebenstein DJ.

HAPPI GWAS: Holistic Analysis with Pre- and Post-Integration GWAS

HAPPI GWAS：集成前后 GWAS 的整体分析

• DOI: 10.1093/bioinformatics/btaa589
• 发表时间: 2020-06
• 期刊: Bioinformatics
• 影响因子: 5.8
• 作者: Slaten, Marianne L;Chan, Yen On;Shrestha, Vivek;Lipka, Alexander E;Angelovici, Ruthie
• 通讯作者: Angelovici, Ruthie

Assessment of two statistical approaches for variance genome-wide association studies in plants

植物方差全基因组关联研究的两种统计方法的评估

• DOI: 10.1038/s41437-022-00541-1
• 发表时间: 2022-05
• 期刊: Heredity
• 影响因子: 3.8
• 作者: Murphy, Matthew D.;Fernandes, Samuel B.;Morota, Gota;Lipka, Alexander E.
• 通讯作者: Lipka, Alexander E.

A High-Throughput Absolute-Level Quantification of Protein-Bound Amino Acids in Seeds

种子中蛋白质结合氨基酸的高通量绝对水平定量

• DOI: 10.1002/cppb.20084
• 发表时间: 2018-11
• 期刊: Current Protocols in Plant Biology
• 作者: Yobi, Abou;Angelovici, Ruthie
• 通讯作者: Angelovici, Ruthie