You may be among the millions of people who have seen a surprisingly specific warning like this on the labels of drugs you take:
Avoid eating grapefruit or drinking grapefruit juice while using this medication.
Such warnings are issued for dozens of substances, including docetaxel, a cancer drug; erythromycin, an antibiotic; and some statins, the cholesterol-lowering drugs prescribed to more than a third of American adults over 40.
The problem is a set of molecules, furanocoumarins. High levels of furanocoumarins interfere with human liver enzymes, among other processes. In their presence, medications can build up to unhealthy levels in the body. And grapefruits and some related citrus fruits are full of them.
But there is no such warning for other kinds of citrus, such as mandarins and other oranges. Citrus researchers at the Volcani Center in Israel reported Wednesday in the journal The New Phytologist that, by crossing mandarins and grapefruit, they’ve uncovered genes that produce furanocoumarins in some citrus fruits. It’s a finding that opens the possibility of creating grapefruit that doesn’t require a warning label.
Scientists had worked out the compounds’ structures and pieced together a basic flowchart of how they are made years ago, said Yoram Eyal, a professor at the Volcani Center. But the precise identities of enzymes catalyzing the process — the proteins that snip off a branch here, or add a piece there — remained mysterious. He and his colleagues knew that one way to identify them was to breed citrus high in furanocoumarins with those without. If the offspring of such a cross had varying levels of the substances, it should be possible, by digging into their genetics, to pinpoint the genes for the proteins.
“We were afraid to approach it, because it’s very time-consuming and it takes many years,” he said, noting how involved it can be to grow new trees from seeds and assess their genetics. “But finally, we decided we have to dive in.”
When they examined the offspring of a mandarin and a grapefruit, the researchers saw something remarkable. Fifty percent of the young plants had high levels of furanocourmains, and 50 percent had none. That particular signature meant something very specific, in terms of how the ability to make these substances is inherited.
“We saw there was only one gene that could have controlled it,” said Livnat Goldenberg, a Volcani Center researcher who is the lead author of the new study.
The researchers soon identified the gene controlling the production of furanocoumarins in leaves and fruit, which produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD for short. Mandarins, it turns out, have a mutated form of this gene that keeps the enzyme from functioning properly. This version cropped up in all the mandarin and orange varieties the researchers checked, explaining why they do not cause the same problems as grapefruit in people taking prescription medications. In these plants, furanocoumarin production is paused.
With gene editing technology, it should be possible to alter the gene in grapefruit as well, Dr. Eyal suggests. The team at the Volcani Center is now exploring that project.
Looking at how widespread this mutated version is in mandarins and some other citrus, the scientists speculate that some gene nearby on the genome must play an important role in a highly prized trait. A long-ago citrus breeder, selecting for some unknown quality, must have unwittingly spread this furanocoumarin-busting version of the gene to an ancestor of modern varieties of mandarins and oranges.
All these years later, that person’s work is coming to light, under the gaze of geneticists, who may, someday, put grapefruit back on the menu.
