Genomic and metabolomic insights into the selection and differentiation of bioactive compounds in citrus

Bioactive compounds play an increasingly prominent role in breeding functional and nutritive fruit crops such as citrus. However, the genomic and metabolic bases for the selection and differentiation underlying bioactive compound variations in citrus remain poorly understood. In this study, we constructed a species-level variation atlas of genomes and metabolomes using 299 citrus accessions. A total of 19 829 significant SNPs were targeted to 653 annotated metabolites, among which multiple significant signals were identified for secondary metabolites, especially flavonoids. Significant differential accumulation of bioactive compounds in the phenylpropane pathway, mainly flavonoids and coumarins, was unveiled across ancestral citrus species during differentiation, which is likely associated with the divergent haplotype distribution and/or expression profiles of relevant genes, including p-coumaroyl coenzyme A 2'-hydroxylases, flavone synthases, cytochrome P450 enzymes, prenyltransferases, and uridine diphosphate glycosyltransferases. Moreover, we systematically evaluated the beneficial bioactivities such as the antioxidant and anticancer capacities of 219 citrus varieties, and identified robust associations between distinct bioactivities and specific metabolites. Collectively, these findings provide citrus breeding options for enrichment of beneficial flavonoids and avoidance of potential risk of coumarins. Our study will accelerate the application of genomic and metabolic engineering strategies in developing modern healthy citrus cultivars.