Search for taste receptors yields sweet success

April 05, 2000

Using biochemical clues as a guide to scout massive databases of genetic sequences, Howard Hughes Medical Institute (HHMI) researchers at Harvard Medical School have identified a family of candidate genes in humans and mice that code for receptors that sense bitter-tasting chemicals.

According to the researchers, the discovery opens the way for the identification of additional receptors that detect bitter and sweet tastes. The finding also gives researchers new probes with which to trace the wiring of the taste perception pathways into the brain itself.

Linda Buck, an HHMI investigator at Harvard Medical School, and her colleagues Hiroaki Matsunami and Jean-Pierre Montmayeur published their findings in the April 6, 2000, issue of Nature.

Buck's group's discovery of bitter taste receptor genes complements recently published findings of the same gene family by another research team led by HHMI investigator Charles Zuker at the University of California, San Diego. Zuker's team published its findings in the March 17, 2000, issue of the journal Cell.

Receptors are proteins that nestle in the cell's surface and bind specific chemicals in much the same way that a key fits into a lock. When activated by a chemical, receptors trigger molecular signals within a cell that alter the cell's metabolism. In the case of taste receptors, chemicals impinging on the taste buds trigger nerve impulses that travel to the brain, where taste information is processed.

Buck and her colleagues began their search by drawing on previous discoveries by other scientists studying taste, including Robert Margolskee, an HHMI investigator at Mount Sinai School of Medicine. Margolskee had obtained evidence that receptors for both bitter and sweet chemicals were coupled to a common signaling molecule inside the cell -- a G-protein that he called gustducin. In launching the search for the genes that expressed such taste-related G-protein coupled receptors (GPCRs), Buck and her colleagues theorized that such receptors would be distantly related to other receptors in the body that signal using other G-proteins.

"In the sense of smell, we previously found one thousand different-but-related odor receptors," said Buck. "Interestingly, these receptors all couple to the same molecules inside the cell to transmit a signal. We suspected that the same would be true for taste."

Buck and her colleagues narrowed their search for taste-related GPCRs to a region of a mouse chromosome that other scientists had found to be involved in the ability to taste a particular bitter substance. Using the Jackson Laboratory Mouse Genome Informatics website, Buck's team pinpointed the promising taste-related region of DNA, called SOA, in the mouse genome and determined that the corresponding region in humans was in a specific location on human chromosome 12. Using the Human Genome Sequence (HGS) database at the National Center for Biotechnology Information, they then scanned that region of chromosome 12 for genes that specify novel receptors distantly related to known GPCRs.

To do this, the scientists used another database containing gene sequence data for known GPCRs. They compared a range of GPCR genes with the DNA sequences available for chromosome 12 in an attempt to detect any similarities. The computer analysis revealed a slight similarity between a particular GPCR gene for a chemical receptor and a chromosome 12 gene in the focus region. Using the chromosome 12 gene for further scans, they uncovered a cluster of related but distinct genes in the same chromosomal region.

"It was like magic," said Buck. "All of a sudden all of these receptor genes showed up that were related, and there was a whole cluster on chromosome 12." Further exploration of the HGS database also revealed related GPCRs on regions of chromosomes 7 and 5 -- the latter of which contains a region of DNA that governs a person's ability to taste a particular bitter chemical.

"We are certain that these receptors are just the tip of the iceberg," said Buck, indicating that more taste receptor genes are sure to surface as the Human Genome Project is completed. "Odorant receptors are known to be scattered throughout the human genome, and we believe the same will be true for taste receptors. We predict that there are probably 50 to 100 of these receptors."

Discovering the candidate taste receptors likely represents only the beginning of a long exploration of the sense of taste, said Buck.

"These findings open the way for a molecular understanding of taste," she said. "For example, we don't know how taste receptors can recognize so many different chemicals with diverse structures, and yet perceive them all has having the same taste, whether bitter or sweet.

"Also, with these receptors, we now have the tools to trace neuronal signals for a particular taste all the way from the taste buds through many connections into the brain. And then we hope to see where the information from the receptor is actually targeted and how it is organized in the brain, and ultimately to learn something about the perception of different tastes."

Howard Hughes Medical Institute

Related Human Genome Articles from Brightsurf:

240 mammals help us understand the human genome
A large international consortium led by scientists at Uppsala University and the Broad Institute of MIT and Harvard has sequenced the genome of 130 mammals and analysed the data together with 110 existing genomes to allow scientist to identify which are the important positions in the DNA.

The National Human Genome Research Institute publishes new vision for human genomics
The National Human Genome Research Institute this week published its 'Strategic vision for improving human health at The Forefront of Genomics' in the journal Nature.

Interpreting the human genome's instruction manual
Berkeley Lab bioscientists are part of a nationwide research project, called ENCODE, that has generated a detailed atlas of the molecular elements that regulate our genes.

3-D shape of human genome essential for robust inflammatory response
The three-dimensional structure of the human genome is essential for providing a rapid and robust inflammatory response but is surprisingly not vital for reprogramming one cell type into another.

The genome of chimpanzees and gorillas could help to better understand human tumors
A new study by researchers from the Institute of Evolutionary Biology (IBE), a joint center of UPF and the Spanish National Research Council (CSIC), shows that, surprisingly, the distribution of mutations in human tumors is more similar to that of chimpanzees and gorillas than that of humans.

It's in our genome: Uncovering clues to longevity from human genetics
Researchers from Osaka University found that high blood pressure and obesity are the strongest factors reducing lifespan based on genetic and clinical information of 700,000 patients in the UK, Finland and Japan.

New limits to functional portion of human genome reported
An evolutionary biologist at the University of Houston has published new calculations that indicate no more than 25 percent of the human genome is functional.

Synthesizing the human genome from scratch
For the past 15 years, synthetic biologists have been figuring out how to synthesize an organism's complete set of DNA, including all of its genes.

Science and legal experts debate future uses and impact of human genome editing in Gender & the Genome
Precise, economical genome editing tools such as CRISPR have made it possible to make targeted changes in genes, which could be applied to human embryos to correct mutations, prevent disease, or alter traits.

Evolution purged many Neanderthal genes from human genome
Neanderthal genetic material is found in only small amounts in the genomes of modern humans because, after interbreeding, natural selection removed large numbers of weakly deleterious Neanderthal gene variants, according to a study by Ivan Juric and colleagues at the University of California, Davis, published Nov.

Read More: Human Genome News and Human Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.