Which odorant receptor allows humans to smell the earthy scent after rain?

For many people, the smell of damp soil after rain carries a fresh, moist, and deeply natural quality. In the food and drinking-water industries, however, that same odor can also be a warning sign. One of the molecules responsible for this earthy or musty smell is geosmin, a volatile sesquiterpenoid of microbial origin. It was first isolated in 1965 from the actinomycete Streptomyces griseus, and later studies showed that the ability to produce this compound is much more widespread among microorganisms, including Nocardia fluminea, the cyanobacterial genus Coelosphaerium, the myxobacterium Myxococcus xanthus, and even the fungus Penicillium expansum.

After rain（Image source：jenny downing， CC BY 2.0 ）

Molecular structure of geosmin（Image source：Calvero，CC0 1.0 ）

Humans are remarkably sensitive to geosmin. In water, we can detect it at concentrations as low as 4 to 10 nanograms per liter. From a chemical and ecological perspective, geosmin serves different roles in different organisms. Some animals are attracted to it, while others avoid it. Mosquitoes can use geosmin as a cue to find suitable oviposition sites. Nematodes and fruit flies may interpret it as a warning signal for the presence of potentially toxic microbes. For animals living in arid environments, the smell of geosmin may also indicate nearby water or moist soil. The same molecule, therefore, can trigger very different behavioral responses across species.

But which odorant receptor allows humans to perceive geosmin? In vertebrates, odor detection mainly depends on odorant receptors located on olfactory sensory neurons in the nose. These receptors belong to the G protein-coupled receptor family. They recognize volatile molecules and convert external chemical signals into information that the nervous system can process. The human genome contains about 400 odorant receptor genes, yet before this study, no clearly geosmin-selective human receptor had been identified. Insects do have known geosmin receptors, such as Or56a in the fruit fly, but insect odorant receptors and human odorant receptors are not necessarily homologous, so the human receptor could not simply be found by tracing an insect counterpart.

Diagram of an olfactory G protein-coupled receptor（Image source：Kang NN and Koo JH. (2012)， CC BY-NC 3.0 ）

The researchers individually expressed 616 human odorant receptors, including allelic variants, in the human HEK-293 cell line. They then exposed these cells to geosmin and examined which receptor triggered G protein-coupled receptor activation. The result was striking: only the odorant receptor OR11A1 showed a clear response to geosmin. The researchers then tested 177 chemically diverse odorants relevant to food aroma. In addition to geosmin, they found that 2-ethylfenchol could also activate OR11A1. These two molecules share similar chemical features: both are bicyclic terpenoid alcohols, and both are associated with musty, muddy, or damp-earth odor qualities. This makes OR11A1 appear to be a sensor tuned toward a particular class of earthy or musty chemical signals.

Predicted structure of the OR11A1 protein（Predicted by AlphaFold）

2-Ethylfenchol（Image source：DrugFuture，CC0 1.0 ）

The researchers also compared OR11A1 orthologs from six mammalian species: the house mouse (Mus musculus), rhesus monkey (Macaca mulatta), Sumatran orangutan (Pongo abelii), polar bear (Ursus maritimus), wild Bactrian camel (Camelus ferus), and Ord's kangaroo rat (Dipodomys ordii). All of these receptors could be activated by geosmin, but their sensitivities differed greatly. Human OR11A1 was among the less sensitive receptors, and the Sumatran orangutan receptor was even less sensitive. By contrast, OR11A1 from Ord's kangaroo rat was extremely sensitive to geosmin, with a half-maximal effective concentration, or EC50, of only 0.24 micromolar. That makes it more than 100 times more sensitive than the human OR11A1 receptor.

Ord's kangaroo rat（Image source：Juan Cruzado Cortés， CC BY 4.0 ）

This difference may reflect lifestyle, diet, habitat, and access to water. Ord's kangaroo rat lives in arid or semiarid environments and can survive with little or no direct access to drinking water, relying instead on plant seeds, cactus-related foods, and arthropods for moisture. If the odor of geosmin helps indicate moist soil, microbial activity, plants, or sites where arthropods gather, then a highly sensitive geosmin receptor could be useful for finding food and water. Humans and orangutans may depend less strongly on such environmental cues, which may explain their weaker receptor sensitivity.

This study gives the biology behind the earthy smell after rain a much clearer molecular foundation. A tiny odor molecule connects the human dining table, animal behavior, microbial metabolism, and the future possibility of receptor-based biosensors in a way that is unexpectedly rich and far-reaching.

Author: Shui-Ye You

References:

1. Ball L et al. (2024). Geosmin, a Food- and Water-Deteriorating Sesquiterpenoid and Ambivalent Semiochemical, Activates Evolutionary Conserved Receptor OR11A1. Journal of Agricultural and Food Chemistry.

2. Kang NN and Koo JH. (2012). Olfactory receptors in non-chemosensory tissues. BMB Rep.