You may be one of the millions of people who have seen a surprisingly accurate warning like this on the labels of medications 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 statinscholesterol-lowering medications prescribed for more than a third of American adults over 40.
The problem is a set of molecules, furanocoumarins. High levels of furanocoumarins interfere, among other processes, with human liver enzymes. In their presence, medications can build up to unhealthy levels in the body. And grapefruit and some related citrus fruits are full of them.
But there is no such warning for other types of citrus fruits, such as tangerines and other oranges. Citrus researchers at the Volcani Center in Israel reported Wednesday in the journal The New Phytologist that by crossing mandarins and grapefruits, they discovered genes that produce furanocoumarins in certain citrus fruits. This is a discovery that opens up the possibility of creating grapefruits that do not require a warning label.
Scientists worked out the structure of the compounds years ago and pieced together a basic flowchart explaining how they are made, said Yoram Eyal, a professor at the Volcani Center. But the precise identity of the enzymes catalyzing the process – the proteins that cut off a branch here or add a piece there – remains mysterious. He and his colleagues knew that one way to identify them was to cross citrus fruits rich in furanocoumarins with others that did not. If the offspring of such a cross showed varying levels of these substances, it should be possible, by digging into their genetics, to identify the genes for the proteins.
“We were afraid to tackle it because it is very time-consuming and takes many years,” he said, noting how complex it can be to grow new trees from seeds and seeds. evaluate their genetics. “But ultimately we decided we had to go for it.”
When they examined the offspring of a tangerine and a grapefruit, researchers saw something remarkable. Fifty percent of the young plants had high levels of furanocourmaines, and 50 percent had none. This particular signature meant something very specific, in terms of how the ability to make these substances is inherited.
“We saw that there was only one gene that could have controlled it,” said Livnat Goldenberg, a researcher at the Volcani Center and lead author of the new study.
Researchers quickly identified the gene controlling furanocoumarin production in leaves and fruits, which produces an enzyme called 2-oxoglutarate-dependent dioxygenase, or 2OGD for short. It turns out that tangerines have a mutated form of this gene that prevents the enzyme from working properly. This version appeared in all varieties of tangerines and oranges checked by researchers, explaining why they don’t cause the same problems as grapefruit in people taking prescription medications. In these plants, furanocoumarin production is interrupted.
Using gene editing technology, it should also be possible to modify the grapefruit gene, Dr Eyal suggests. The Volcani Center team is currently exploring this project.
By examining the extent of this mutated version in mandarin oranges and some other citrus fruits, scientists hypothesize that a gene close to the genome must play an important role in a highly prized trait. Long ago, a citrus breeder, breeding for an unknown quality, must have unwittingly passed on this version of the gene that destroys furanocoumarin to an ancestor of modern varieties of mandarins and oranges.
All these years later, this man’s work has come to light, under the gaze of geneticists, who will perhaps one day put grapefruit back on the menu.