Nearly a million genetic variations across about 400 smell receptors mean everyone experiences scent differently.

Why People Smell Things Differently: Genetics of Odor Receptors

A tiny difference in DNA — a single amino acid change in one odor receptor gene — can determine whether you find a particular scent pleasant or unpleasant. That same gene in a friend, with a different amino acid, can produce the opposite reaction. This variability helps explain why people often disagree about how something smells.

Humans have roughly 400 genes that encode the receptors in our noses. According to large-scale genomic surveys, there are more than 900,000 variations in those genes. Those variations alter the proteins that form olfactory receptors, and a specific odor activates a pattern of receptors in the nose to create a unique signal that the brain interprets as a smell.

The image shows a woman smelling a flower. — Researchers tested each receptor with low concentrations of many odor molecules to identify which receptors respond. This illustrative photo shows a woman smelling a flower. Image credit noted below.

“There are many cases when you say you like the way something smells and other people don’t. That’s very common,” said Hiroaki Matsunami, Ph.D., associate professor of molecular genetics and microbiology at Duke University School of Medicine. His team’s work indicates that no two people smell in the same way at the receptor level. When comparing the odor receptor proteins of any two individuals, about 30 percent of receptor sequences differ — and that estimate is likely conservative because it excludes highly variable promoter regions and gene copy number differences.

Until recently, researchers had identified the genes for odor receptors but still lacked a clear understanding of how specific receptors are activated by odor molecules. To address this, Matsunami and colleagues cloned more than 500 receptor variants from 20 individuals. Each receptor differed by only one or two amino acids from related forms. The team then systematically exposed those receptors to a panel of odorants to observe which chemicals activated which receptors.

Using small concentrations — 1, 10, or 100 micromoles — of 73 odorants (including molecules like vanillin and guaiacol), the researchers identified 27 receptors that showed significant responses to at least one odorant. This discovery, published in Nature Neuroscience, doubled the number of odorant-activated human receptors known at the time, bringing the total to 40 receptors with identified activating molecules.

These findings have practical implications. Industries focused on flavors, fragrances, and food ingredients currently rely heavily on trial-and-error when developing new scents and tastes. By mapping which receptors respond to specific chemicals and understanding the downstream effects of those activations, manufacturers could adopt more rational, science-based approaches to design new perfumes, flavorings, or scent additives.

Research Team, Funding, and Publication

The study’s co-authors include Joel D. Mainland, Casey Trimmer, Lindsey L. Snyder, and Andrew H. Moberly from Monell Chemical Senses Center and the University of Pennsylvania School of Medicine, and Andreas Keller from The Rockefeller University, along with other collaborators. Funding for the research came from the National Institutes of Health.

Contact: Karl Leif Bates – Duke University

Original research: “The missense of smell: functional variability in the human odorant receptor repertoire,” by Joel D. Mainland et al., published in Nature Neuroscience. DOI: 10.1038/nn.3598.

Image credit

Photo credited to PublicDomainPictures and released into the public domain.

Keywords: neuroscience, odor, olfaction, olfactory receptors, neurogenetics, Duke University, odorant receptors, scent perception