Teams find probable gene for sweet sense

Two scientific groups tasted victory this week in a race to identify a candidate gene for controlling our proverbial sweet tooth. The two teams pulled ahead of several others scrambling to describe the genetic basis of sweet-taste perception

in mammals.

“It’s been a kind of dogfight,” says Danielle R. Reed, a behavioral geneticist on a team at the Monell Chemical Senses Center in Philadelphia. By reporting their

work simultaneously in the May Nature Genetics and the May Nature Neurobiology,

two Howard Hughes Medical Institute labs–one at Mount Sinai School of Medicine in

New York and the other at Harvard Medical School in Boston–squeaked by Reed’s team

and several others.

The tongue distinguishes only five basic flavors: sweet, sour, bitter, salty, and

umami, the taste associated with monosodium glutamate. Unveiling how tongue cells

register these flavors has been a challenge, especially for the umami, bitter, and

sweet flavors, which depend on receptors made of protein. In contrast, salty and,

probably, sour flavors use a simpler detection system.

Scientists have recently identified the genes for proteins that serve as the

molecular receptors for the umami and bitter categories (SN: 1/29/00, p. 68;

3/25/00, p. 196). The gene for sweet receptors, however, remained elusive.

“Three things were essential in finding this gene” in humans, says Nicholas J.P.

Ryba of the taste and smell unit of the National Institute of Dental and

Craniofacial Research in Bethesda, Md. Researchers needed an idea of the sequence

of a sweet-receptor gene and some sense of where in the genome it might be found.

They also required the human genome sequence.

Two years ago, two genes that are active in human taste cells and that resemble

other genes already associated with sensory receptors were identified by Ryba’s

team in conjunction with Charles Zucker of the Howard Hughes Medical Institute at

the University of California, San Diego. These genes provided examples of what a

sweet-sensing gene might look like (SN: 2/27/99, p. 132).

Gary K. Beauchamp and Alexander Bachmanov of Monell then localized sweet

sensitivity in mice to a small genomic region called the Sac locus (SN: 4/15/00,

p. 255). Reed, a member of the Beauchamp team, describes this narrowing of the

search as “starting out by looking throughout the world and ending up looking

under the sofa cushions.”

Finally, the unveiling of the human genome sequence earlier this year enabled the

researchers hunting for sweet-receptor genes to troll the stretches of human DNA

that are analogous to the mouse’s Sac locus. The researchers targeted genes with

sequences resembling those for the receptors that Ryba and Zucker found in 1999.

“We were combing the whole region responsible for the sweet [taste sensitivity]

and basically found one novel receptor,” says Y. Gopi Shanker of the Mount Sinai

team. The other group, headed by Jean-Pierre Montmayeur of Harvard Medical School,

took a similar tack.

In their reports, both groups described the receptor’s gene, called T1r3, as the

likely basis for the tongue’s sweetness sensor. The teams are now attempting to

confirm the function of the gene by disabling it in mice and in cell cultures and

measuring sensitivity to sweetness.

Deciphering the molecular mechanisms behind taste will lead to a better

understanding of perception in general, says Montmayeur. Specifically, he adds,

researchers want to understand why some people crave sugar to their own detriment and how artificial sweeteners might better fool the palate.