Extensive variability in olfactory receptors influences human odor perception

In color vision, genetic variation in a single type of visual receptor leads to red-green colorblindness. Similar to the visual system, genetic variation in the olfactory system can alter perception of the olfactory world. This image was inspired by the Ishihara Color Blindness test, where colorblind individuals are unable to identify the embedded image inside each circle. Credit: Joel Mainland

According to Gertrude Stein, "A rose is a rose is a rose," but new research indicates that might not be the case when it comes to the rose's scent. Researchers from the Monell Center and collaborating institutions have found that as much as 30 percent of the large array of human olfactory receptor differs between any two individuals. This substantial variation is in turn reflected by variability in how each person perceives odors.

Humans have about 400 different types of specialized sensors, known as olfactory receptor proteins, that somehow work together to detect a large variety of odors.

"Understanding how this huge array of receptors encodes odors is a challenging task," says study lead author Joel Mainland, PhD, a molecular biologist at Monell. "The activation pattern of these 400 receptors encodes both the intensity of an and the quality – for example, whether it smells like vanilla or smoke – for the tens of thousands of different odors that represent everything we smell.

Right now, nobody knows how the activity patterns are translated into a signal that our brain registers as the odor."

Adding to the complexity of the problem, the underlying amino acid sequence can vary slightly for each of the 400 receptor proteins, resulting in one or more variants for each of the receptors. Each receptor variant responds to odors in a slightly different way and the variants are distributed across individuals such that nearly everyone has a unique combination of .

To gain a better understanding of the extent of olfactory receptor variation and how this impacts human odor perception, Mainland and his collaborators used a combination of high-throughput assays to measure how single receptors and individual humans respond to odors. The results, published in Nature Neuroscience, provide a critical step towards understanding how olfactory receptors encode the intensity, pleasantness and quality of .

The researchers first cloned 511 known variants of human olfactory receptors and embedded them in host cells that are easy to grow in the laboratory. The next step was to measure whether each receptor variant responded to a panel of 73 different odor molecules. This process identified 28 receptor variants that responded to at least one of the odor molecules.

Drilling down, the researchers next examined the DNA of 16 , discovering considerable variation within the genes for discrete receptors.

Using sophisticated mathematical modeling to extrapolate from these results, Mainland predicts that the olfactory receptors of any two individuals differ by about 30 percent. This means that for any two randomly chosen individuals, approximately 140 of their 400 olfactory receptors will differ in how they respond to odor molecules.

To understand how variation in a single olfactory receptor affects odor perception, the researchers studied responses to odors in individuals having different variants of a receptor known as OR10G4. They found that variations in the OR10G4 receptor were related to how people perceive the intensity and pleasantness of guaiacol, a molecule that often is described as having a 'smoky' characteristic.

Moving forward, a current study is relating the olfactory receptor repertoire of hundreds of people with how those people respond to odors. The data will enable the researchers to identify additional examples of how changes in individual receptors affect olfactory perception.

"The long-term goal is to figure out how the receptors encode odor molecules well enough that we can actually create any odor we want by manipulating the directly," said Mainland. "In essence, this would allow us to 'digitize' olfaction."

More information: The missense of smell: functional variability in the human odorant receptor repertoire, DOI: 10.1038/nn.3598

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not rated yet Dec 08, 2013
The truth revealed in the context of amino acid substitutions is that the theory of mutation-driven evolution does not make sense and it never did.

See for example: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

"...the epigenetic 'tweaking' of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution."

One reason you may not know this yet is that you were taught to believe in a theory that was never supported by experimental evidence from any species.

See for review: An experimental test on the probability of extinction of new genetic variants.

not rated yet Dec 09, 2013
For contrast, note the insistence by the moderator of the International Society for Human Ethology's yahoo group. He thinks that random mutations are the substrates on which directional natural selection acts. This is what happened when I told him that natural selection is for food:


Jay R. Feierman, best known to me for his ridiculous question: "What about birds?" wrote:

"It is very sad for me to see that when several different people on this group, all with doctorate degrees, tell you that you are not correct, you don't consider that they might be telling you something helpful. Instead, you respond with arrogance and ignorance. I'll add my voice to the other people on this group who have told you that you are not correct in terms of your understanding of what "variation" means in Darwinian biological evolution and what is doing the selecting. Variation is not nutrient availability..."

This evidence shows that it is!