Foxtail millet (Setaria italica), which was domesticated from the wild species green foxtail (Setaria viridis), is a rich source of phytonutrients for humans. To evaluate how breeding changed the metabolome of foxtail millet grains, we generated and analyzed the datasets encompassing the genomes, transcriptomes, metabolomes, and anti-inflammatory indices from 398 foxtail millet accessions. We identified hundreds of common variants that influence numerous secondary metabolites. We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet. Furthermore, we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones. Using CRISPR-mediated genome editing we validated the function of PHYTOENE SYNTHASE 1 (PSY1) gene in affecting millet grain color and quality. Interestingly, our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects. Taken together, our multi-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile. The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites, laying the foundations for future millet genetic research and metabolome-assisted improvement.

谷子 ( Setaria italica )，由野生物种绿谷子 ( Setaria viridis ) 驯化而成)，是人类植物营养素的丰富来源。为了评估育种如何改变谷子的代谢组，我们生成并分析了包含来自 398 个谷子种质的基因组、转录组、代谢组和抗炎指数的数据集。我们确定了数百种影响许多次生代谢物的常见变体。我们观察到谷子不同亚群之间代谢物的自然变异及其潜在遗传结构的巨大差异。此外，我们发现与黄色谷物相关的基因等位基因的选择导致代谢物如类胡萝卜素和内源性植物激素的谱发生变化。使用 CRISPR 介导的基因组编辑，我们验证了PHYTOENE SYNTHASE 1的功能（PSY1 )基因影响小米粒色和品质。有趣的是，我们的体外细胞炎症试验表明，小米中的 83 种代谢物具有抗炎作用。总之，我们的多组学研究说明了谷子的育种历史是如何塑造其代谢物特征的。我们在本研究中生成的数据集也为进一步了解不同代谢物对小米籽粒品质的影响提供了重要资源，为未来小米遗传研究和代谢组辅助改进奠定了基础。