Team of Icelandic scientists find gene variant that makes rotten fish smell like caramel

In one of the largest studies of its kind ever conducted, researchers have homed in on a specific gene variant that influences how strongly a person perceives rotten fishy odors. The study also for the first time identified gene variants associated with the intensity of licorice and cinnamon odors.

Our sense of smell is primarily governed by olfactory receptors in our nasal cavity. An odor molecule binds to receptor sites which subsequently send signals to parts of our brain responsible for processing smells. Of course, our responses to smells are complex, deeply intertwined with emotions and experiences, however, olfactory receptor sensitivity is also strongly influenced by genetics.Perhaps the most well-known genetically influenced taste/smell is the infamous soapy cilantro. It is thought around 10 percent of people carry a genetic variant making their olfactory receptors particularly susceptible to sensing a molecule in cilantro responsible for a characteristic pungent soapy aroma.

How olfactory genes influence human perception of certain smells is notably understudied. To shed some light on these mysteries, a large team of Icelandic scientists recruited over 9,000 subjects. Each participant subjectively reported responses to six key odors: licorice, cinnamon, fish, lemon, peppermint and banana.

“We discovered sequence variants that influence how we perceive and describe fish, licorice, and cinnamon odors,” explains one of the study’s authors, Rosa Gisladottir from deCODE Genetics in Reykjavik. “Since our sense of smell is very important for the perception of flavor, these variants likely influence whether we like food containing these odors.”

The most striking, and novel, genetic variant uncovered related to odor sensitivity for a molecule called trimethylamine (TMA). This particular compound is fundamentally responsible for that highly familiar smell of rotten fish.A genetic variant in an olfactory receptor gene called trace amine-associated receptor 5 (TAAR5) was found to significantly reduce a person’s negative perception of TMA. In fact, the study even found some subjects with the genetic variant responded positively to the smell of TMA, describing it as similar to “caramel” or “rose”.

“Carriers of the variant find the fish odor less intense, less unpleasant, and are less likely to name it accurately,” says Gisladottir. “There is a lot of animal research on TAAR5 in relation to its role in hard-wired aversive responses to trimethylamine. Our findings extend the implications of this research to human odor perception and behavior.”

Unlike the TMA genetic variant discovery, the other two discoveries in the study referred to variants seen to increase smell perception. Two genetic variants were identified that could be associated with increased odor intensity for licorice and cinnamon.

“We discovered a common variant in a cluster of olfactory receptors which is associated with increased sensitivity to trans-anethole, found in black licorice products but also in spices and plants such as anise seed, star anise, and fennel,” adds Gisladottir. “Carriers of the variant find the licorice odor more intense, more pleasant, and can name it more accurately. Interestingly, the variant is much more common in East Asia than in Europe.”

It is early days for this kind of research, but the study does note there appears to be significant geographical diversity in these olfactory receptor gene variants. The researchers ultimately conclude our human sense of smell is very much still being honed through processes of natural selection.

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