You may be among the millions of people who have seen surprisingly specific warnings on the labels of the medications you take:
Do not eat grapefruit or drink grapefruit juice while using this medicine.
Such warnings have been issued for dozens of substances, including the cancer drug docetaxel. Erythromycin, an antibiotic. Some statins are cholesterol-lowering drugs that are prescribed to more than one-third of American adults over the age of 40.
The problem is a group of molecules called furanocoumarins. High levels of furanocoumarins interfere with human liver enzymes, among other processes. If drugs are present, they can accumulate to unhealthy levels in the body. Grapefruit and related citrus fruits are rich in them.
However, other types of citrus fruits, such as tangerines and other oranges, have no such warning. Citrus researchers at Israel's Volcano Center reported Wednesday in the journal New Phytologist that they have discovered a gene that produces furanocoumarins in some citrus fruits by crossing mandarin and grapefruit. This is a discovery that opens up the possibility of creating grapefruit that don't require warning labels.
Scientists had worked out the structure of the compound years ago and compiled a basic flowchart for how to make it, said Professor Yoram Eyal of the Volcano Center. But the exact identity of the enzymes that catalyze this process, the proteins that cut off branches and add fragments to them, remained a mystery. He and his colleagues knew that one way to tell them apart was to cross-breed citrus fruits with and without furanocoumarins. If the offspring of such a cross had varying levels of a substance, a closer look at their genetics should pinpoint the gene for the protein.
“We were afraid to tackle it because it's so time-consuming and takes years,” he says, explaining how complex it is to grow a new tree from seed and evaluate its genetic characteristics. He pointed out that “But ultimately we decided we had to jump in.”
When examining the descendants of mandarin and grapefruit, researchers noticed something remarkable. Fifty percent of the young plants contained high levels of furanocurmaine, and the remaining 50 percent contained no furanocurmaine. That particular characteristic meant something very specific in terms of how the ability to make these substances was inherited.
“We found that there is only one gene that can control it,” said Volcano Center researcher Livnat Goldenberg, lead author of the new study.
Researchers quickly identified genes that control the production of furanocoumarins in leaves and fruits. This gene produces an enzyme called 2-oxoglutarate-dependent dioxygenase (2OGD for short). It turns out that mandarin oranges have a mutant form of this gene that prevents the enzyme from functioning properly. This version occurred in all mandarin and orange varieties the researchers tested, explaining why it doesn't cause the same problems as grapefruit in people taking prescription drugs. Furanocoumarin production has been temporarily suspended at these factories.
Eyal suggests that gene-editing techniques could also be used to change the genes of grapefruit. A team at the Volcano Center is currently investigating the project.
Seeing how widespread this variant is in mandarins and other citrus fruits, scientists believe that several genes nearby on the genome must play an important role in the highly valuable trait. I'm guessing not. Long ago, citrus breeders must have selected for an unknown quality and unwittingly spread this furanocoumarin-destroying version of the gene to the ancestors of modern mandarin and orange varieties.
Years later, that man's research has come to light under the watchful eyes of geneticists, and may one day put grapefruit back on the menu.
