News and Views

Nature 404, 552-553 (6 April 2000) | doi:10.1038/35007167

Neurobiology: The good taste of genomics

Stuart Firestein

Be it an expensive dinner or a quick snack, the complexity of a flavour results from the multimodal nature of the perception. A flavour is affected by smell, touch and even pain (hot and cold) inputs, all of which are wedded to the tastes detected by sensory cells on the tongue. The four primary tastes are salty, sour, bitter and sweet. More recently, a fifth taste — umami — has come to be recognized as an independent sensation; this is common in Asian cuisines and is the taste of the amino acid glutamate. But how are these tastes detected? Thanks to a remarkable concurrence of papers1, 2, 3, we are now several steps closer to answering this question. Matsunami and colleagues, writing on page 601of this issue1, and Adler et al. and Chandrashekar et al., reporting in a recent issue of Cell2, 3, have been mining genomic data, and have struck gold with their discovery of a new family of bitter-taste receptors in mice and humans.

The biochemical and physiological mechanisms by which tastes are detected and discriminated are quite different. Salty and sour tastes, for example, result simply from the influx of sodium ions (for salty tastes) or hydrogen ions (for sour tastes) through channels in the uppermost membranes of taste-receptor cells (TRCs). By contrast, the sweet, bitter and umami tastes were thought to be detected by receptors that bind to a specific taste molecule. These receptors were presumed to be linked to guanine-nucleotide-binding (G) proteins, well-known components of intracellular signalling cascades. However, the precise mechanisms involved and the identities of the molecular players remained unclear. This is where the new papers1, 2, 3 come in. As predicted, the bitter-taste receptors in mice and humans do indeed make up families of previously unknown G-protein-coupled receptors (GPCRs). Why has this result been so long in coming, and what was the breakthrough?

The problem has been that most of the tongue has nothing to do with taste. TRCs are packed into small, onion-shaped structures called taste buds, with from 50 to 100 cells in a single bud. There are only a few thousand taste buds and perhaps 30,000–50,000 TRCs, which are hard to isolate and do not provide much material with which to work. The solution has been provided by the progressive sequencing of the human and mouse genomes, and the ever-increasing amount of sequence data available in public databases.

Starting in humans, Matsunami et al.1, Adler et al.2 and Chandrashekar et al.3 had an important lead: there is a known genetic variation that results in reduced sensitivity to a bitter substance known as PROP. This variation maps to a particular region of the human genome for which a significant amount of sequence was already available. This is where the hunt for genes encoding taste receptors began. The hypothesis was that, because there are a lot of chemically different bitter substances (Fig. 1), there would be a large family of receptors to recognize them; this family might be encoded by a gene cluster, mapping to a tight region of the genome, perhaps near the known site of variation. Indeed, the authors did identify candidate genes for taste receptors in this region (in retrospect, this was probably fortuitous because the PROP-sensitivity gene turns out not to encode a taste receptor). Using the sequences of these genes to search further in the genome, the groups identified another 19 related genes, spread over three chromosomes. A new family of receptors was born.

Figure 1: Leaving a bitter taste in the mouth.
Figure 1 : Leaving a bitter taste in the mouth. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact

The chemical structures of even these few bitter substances are very diverse. This leads one to suspect that there must be a family of bitter-taste receptors in the tongue — a family that has now been identified by Matsunami et al.1, Adler et al.2 and Chandrashekar et al.3.

High resolution image and legend (10K)

A cluster of genes encoding GPCRs also mapped to a region of the mouse genome homologous to that of the human region. This allowed the critical molecular proof to be developed in mice. The messenger RNA encoding the receptors was present in a subset of TRCs in mice, and expression of these receptors was highest in taste tissue. Finally, when the receptors were expressed in cultured mouse cells, the cells responded to specific bitter substances. This strategy makes plain the importance of having multiple genome sequences available for research. Rigorous proof of the function of these genes would have been nearly impossible to obtain in humans.

But have all the bitter-taste receptors now been identified? The answer is probably not, as only 14% of the human genome was available to be searched. Taking into account the existence of 'pseudogenes', and the fact that the taste-receptor genes are probably not distributed randomly across the genome, there could be between 50 and 90 receptors in all.

Interestingly, it seems that a given taste cell makes many, perhaps all, of the receptors. If a single cell makes many receptors, it will be sensitive to many bitter compounds, but the brain will not be able to distinguish which particular bitter substance is being detected. Indeed, humans often cannot distinguish between bitter stimuli. Bitter substances are frequently poisonous or harmful and need to be detected at low concentrations, before a fatal amount of something is swallowed. But because bitter substances include many different types of chemical (Fig. 1), a single receptor that recognized many bitter compounds could not be very sensitive to any one of them. The strategy of expressing multiple receptors, each recognizing a specific bitter taste, results in TRCs with a broad range but high sensitivity.

Victor Hugo once claimed that nothing is as powerful as an idea whose time has come, and this certainly seems to be true of taste receptors. Just a few weeks ago came the report4 of a new family of receptors in the fruitfly Drosophila melanogaster that were distinct from the fly odour receptors but were also found in chemosensory organs. These new receptors seem to be the fly taste receptors, another distinct family of GPCRs. Finally, there is the curious taste umami — the taste of glutamate. We have glutamate receptors in the brain, for glutamate is an important neurotransmitter. But glutamate activates the brain glutamate receptors, called mGluRs, at concentrations that are far below taste thresholds. Chaudhari et al.5 reported recently that an alternatively spliced isoform of mGluR4, with a more appropriate affinity for glutamate, is expressed in a subset of TRCs, so this may be the umami detector.

The taste field has had quite a start to the millennium. Where do we go from here? Taste is important in many areas of our lives. Caloric intake and salt ingestion are two obvious areas that might benefit from an understanding of the underlying taste mechanisms. Many medicines have a terribly bitter taste — so much so that patient compliance is often compromised. The development of bitter antagonists is now within reach, allowing us to increase the palatability of medicines and even of foods that are 'good' for you. Insect pests identify feeding and breeding plant hosts by taste, raising the possibility of controlling such pests by tastes rather than by toxic and environmentally harmful insecticides. Of course these developments are not trivial, and nor are the remaining questions — the identity of the sweet receptor, for example. But with the receptors that we now have and the application of a similar strategy to the newly available genome data, it should be well within our power to lick these problems.



  1. Matsunami, H. , Montmayeur, J.-P & Buck, L. B. Nature 404, 601– 604 (2000). | Article | PubMed | ISI | ChemPort |
  2. Adler, E. et al. Cell 100, 693–702 (2000). | Article | PubMed | ISI | ChemPort |
  3. Chandrashekar, J. et al. Cell 100, 703–711 (2000). | Article | PubMed | ISI | ChemPort |
  4. Clyne, P. J. , Warr, C. G. & Carlson, J. R. Science 287, 1830– 1834 (2000). | Article | PubMed | ISI | ChemPort |
  5. Chaudhari, N. , Landin, A. M. & Roper, S. D. Nature Neurosci. 3, 113– 119 (2000).