A single gene that codes for one odor receptor (of more than 400 functional receptors in humans) can determine whether someone perceives a particular steroid derivative of testosterone as odorless, smelling like urine—or sweet vanilla.

A team of scientists at the Duke University Medical Center in Durham, N.C., and The Rockefeller University in New York City had nearly 400 blood-tested volunteers sniff 66 scents to determine whether there is a genetic link to the way an individual perceives the odor of androstenone (a key component in male sweat and urine).

The results of the study, published in Nature, indicate that a person's perception of the pheromone (a chemical that conveys information between individuals within a species) androstenone is largely determined by an odor receptor known as OR7D4; variations in the gene that codes that receptor influence the spectrum of responses people have to the scent of androstenone as well as a related chemical androstadienone (also found in male sweat and urine).

"In my mind, this work represents the first example of a direct link between genetic variability in olfactory receptor genes and differences in the sense of smell," says Yoav Gilad, a professor of human genetics at the University of Chicago, who was not involved in this study.

The Rockefeller team, led by Leslie Vosshall, an associate professor of neurogenetics and behavior, directed 391 volunteers to sample the scents (ranging from spearmint to banana to butanol) in two different concentrations and describe how they smelled. Researchers in the lab of Hiroaki Matsunami, an assistant professor of molecular genetics and microbiology at Duke analyzed the subjects' DNA in an attempt to determine whether a person's perception of androstenone smells can be traced to variations in the gene for OR7D4, previously found to interact with the steroid.

Matsunami's team found two variations (or alleles) of the gene associated with different characterizations of androstenone's smell: Subjects with two "normal" copies of the gene, about 62 percent of the study population, described androstenone's aroma as having an intense, unpleasant odor similar to that of urine. If a person had one of each allele, he or she described the scent as ranging from imperceptible to unpleasant, but not intense.

Only 10 of the study participants had two copies of the mutated gene, according to Hanyi Zhuang, a graduate student in Matsunami's lab. "[These] subjects indeed show even lower intensity ratings to androstenone and androstadienone in our study," she says, and even described the smell of the steroids as sweet, like vanilla. The fact that some [of these] subjects could smell androstenone, she continues, "suggests additional odorant receptors are activated by these chemicals."

Zhuang believes that the odor receptor has likely been shaped by evolution, because of the role the scent of androstenone and androstadienone plays in evaluating mates. "One aspect of it is whether we can find evidence that odorant receptor variants play any roles in physiological changes caused by exposure of these sex steroid–derived odors," she says. "In other words, people who have two copies of functional variants might show more changes in mood or hormonal levels when exposed to androstenone or androstadienone."