Androstenone is a derivative of testosterone that is a potent ingredient in male body odor. To some it smells like stale urine, others find it sweet and pleasant. Some can't smell it at all.

Androstenone is used by some mammals to convey social and sexual information so if you know a girl who doesn't like the way you smell, it may be genetic variations in a single odorant receptor called OR7D4 - don't take it personally, it's in her genes.

Researchers at Rockefeller University presented nearly 400 participants with 66 odors at two different concentrations and asked them to rate the pleasantness and intensity of each odor. When scientists at Duke University identified OR7D4 as a receptor that androstenone selectively activates, Leslie Vosshall, Chemers Family Associate Professor and head of the Laboratory of Neurogenetics and Behavior at Rockefeller University and Andreas Keller, a postdoc in her lab, formed a collaboration with them, and began collecting blood samples from participants and isolated their DNA. The Duke team, led by Hiroaki Matsunami, used DNA from each participant to sequence the gene that encodes the OR7D4 receptor.

"With this large dataset, we are able to say that people who express different variants of this receptor perceive this odor differently," says Vosshall.

Although it has long been suspected that the ability to perceive the odor of androstenone is genetically determined, this study is the first to identify variations in a single gene that account for a large part of why people perceive androstenone's scent so differently.

With their Duke collaborators, Vosshall and Keller identified two point mutations called single nucleotide polymorphisms along the gene, which gave rise to two variants of the odorant receptor: RT and WM, which differ by two amino acids. As a group, participants with the RT/RT genotype perceive androstenone's odor as foul and intense. Those with the RT/WM genotype, on the other hand, are more likely to perceive androstenone as less unpleasant. Many cannot smell androstenone at all. Although some participants with the RT/WM genotype can smell androstenone, they experience the smell very differently than those with two copies of the fully functional receptor: To them, androstenone doesn't smell like urine; it has a vanilla scent.

"There are two independent things that are interesting about this odor," says first co-author Keller. "One is that it is a potential social signal but the other one is that so many people cannot smell it."

Two additional point mutations in some of the participants influenced their sensitivity to androstenone, one of which may make humans hypersensitive to this odor. Vosshall and Keller are interested in what it is about these amino acid changes that alter one's perception of androstenone's scent, and in whether one's perception of this potent compound can influence behavior.

"Since some mammals clearly use androstenone to communicate sexuality and dominance within a social hierarchy, it's intriguing to think whether the same thing may happen in humans," Vosshall says. "If so, what happens to humans who can't get the signal because they have the nonfunctional copy of the gene? Or the hyperfunctional one? What could be the social and sexual implications of this on one's perception of the smell of fellow humans?"

- Rockefeller University