You may be among the millions of people who have seen incredibly specific warnings on the labels of the medications you take:
Avoid eating grapefruit or drinking grapefruit juice while using this medicine.
Such warnings are issued for dozens of substances, including docetaxel, a cancer drug; erythromycin, an antibiotic; And Some statinscholesterol-lowering drugs were prescribed. More than one-third of American adults over 40.
The problem is a collection of molecules, furanocoumarins. High levels of furanocoumarins interfere with human liver enzymes, among other processes. In their presence, drugs can build up in the body to unhealthy levels. And grapefruit and some related citrus fruits are full of them.
But there is no such warning for other types of citrus, such as mandarins and other oranges. Sour researchers at the Volcanic Center in Israel reported on Wednesday By crossing mandarins and grapefruits, they uncovered genes that produce furanocoumarins in some citrus fruits, the journal The New Phytologist wrote. It’s a finding that opens up the possibility of creating grapefruit that doesn’t require a warning label.
Yoram Eyal, a professor at the Volcanology Center, said scientists had worked out the structures of the compounds and put together a basic flowchart of how they form years ago. But the exact identity of the enzymes catalyzing the process — the proteins that break off a branch here, or add a fragment there — remains elusive. He and his colleagues knew that one way to identify them was to breed citrus fruits high in furanocoumarins with those without. If the offspring of such crosses have different levels of the substances, it should be possible to dig into their genetics and identify the gene for the protein.
“We were afraid to approach it, because it’s very time-consuming and takes years,” he said of the process involved in growing new trees from seeds and assessing their genetics. “But eventually, we decided we had to dive in.”
When they examined the offspring of a mandarin and a grapefruit, the researchers noticed something remarkable. Fifty percent of young plants had high levels of furanocormins, and 50 percent had none. This particular signature meant something special, in terms of how the ability to make these substances was inherited.
“We found that there was only one gene that could control it,” said Leont Goldenberg, a researcher at the Volcanology Center who is lead author of the new study.
Researchers soon identified the gene controlling the production of furanocoumarins in the leaves and fruit, which produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD for short. It turns out that mandarins have a mutated form of this gene that prevents the enzyme from working properly. The prescription worked in all the mandarin and orange varieties the researchers checked, explaining why they didn’t cause the same problems as grapefruit in people taking prescription drugs. In these plants, the production of furanocoumarin is inhibited.
Dr. Eyal suggests that with gene editing technology, it should be possible to change genes in grapefruit as well. The Volcano Center team is now exploring the project.
Given how widespread this mutated version is in mandarins and some other citrus, scientists hypothesize that some gene close to the genome must play an important role in a highly prized trait. A long-ago citrus breeder, selecting for an unknown quality, may have inadvertently spread this furanocoumarin-busting version of the gene to the ancestors of modern varieties of mandarins and oranges.
All these years later, the man’s work is catching the eye of geneticists, who may someday put grapes back on the menu.