Furanocoumarin Inheritance and Biosynthesis Gene Characterization in Grapefruit

Furanocoumarins (FCs) are a class of secondary organic chemical components in which basic chemical structure has a furan ring fused with coumarin. Clinically reported, certain types of FCs in grapefruit juice could cause potentially deleterious interactions with some drugs, called grapefruit juice effect, when the FCs increase the bioavailability of these drugs through inhibition of some cytochrome P450 isoforms, the human intestinal enzyme responsible for the drug metabolism. In this study we measured seven FCs (bergamottin, 6’,7’-dihydroxybergamottin  (6,7-DHB), paradisin C, bergaptol, isoimperatorin, 5’,8’-dimethylallyloxypsoralen (5,8-DMP), and epoxybergamottin (EBM), in selected grapefruit (Citrus paradisi), pummelo (C. maxima)  cultivars, and their hybrids, and characterized important unigenes representing possible functional genes in the furanocoumarin (FC) biosynthetic pathways by digital gene expression profiling and experimental expression validation. Based on all the cultivars and hybrids, strong correlations existed among 6,7-DHB, bergamottin, and paradisin C (coefficient up to 0.909), and  most intriguingly, the three FCs obviously co-segregated, in an approximate rate of 1:1 among all the randomly selected hybrids. The strong correlation and 1:1 co-segregation among the three FCs likely reflected their metabolic links and suggested one single enzymatic or regulatory gene controlling the trait of FCs in the bergamottin pathway. In addition, the inference was further supported by genomic heterozygosity and expressed differentiation found among some important genes in the pathway between a parent of high FCs and its low-FC mutant. The inheritance model and gene expression information may facilitate further genetic mapping of those genes and identification of key genes controlling FC biosynthesis in grapefruit, and lead to a genomic and breeding solution to the grapefruit FC-drug interaction issue.