News Release

On the nose

Are humans and other animals equally equipped to sniff out pheromones? No, says one USC researcher, whose studies suggest that evolution eliminated our ability long ago.

Peer-Reviewed Publication

University of Southern California

A pair of tiny pits in the human nose are at the center of a longstanding debate over whether people can pick up on powerful chemical signals, or pheromones, that influence sexual and other behaviors throughout the animal kingdom.

In animals ranging from single-celled organisms to orangutans, pheromones do everything from triggering mating to establishing boundaries.

In humans, the best proof that people release pheromones can be seen in menstrual synchrony – when women living in a college dorm, for example, all menstruate around the same time.

But there is still debate over whether humans have a physiological tool critical to detecting pheromones – the vomeronasal organ.

"That's where we come in," said Emily Liman, whose new USC study traces the disappearance of a gene essential to the functioning of the vomeronasal organ in our primate ancestors.

When mutations wiped out that gene, she contends, primates also lost functioning of the vomeronasal organ. The mutations started happening roughly 40 million years ago in the common ancestor of Old World monkeys, apes and humans.

That may explain, Liman said, why all that humans have to show for a vomeronasal organ are two pits in the nasal septum, the cartilage that divides the nostrils. Some scientists think it still functions while others, including Liman, consider it only a vestigial organ.

"There has been a lot of controversy about whether humans have a vomeronasal organ," said Liman, an assistant professor of biological sciences in the USC College of Letters, Arts & Sciences.

Liman and her colleague, Hideki Innan, a postdoctoral fellow in computational biology at USC, studied the DNA of a large number of primate species. They looked specifically for mutations in TRPC2 – a gene Liman discovered in the late 1990s while an instructor of neurobiology at Harvard Medical School.

Studying mice at Harvard, Liman discovered the TRPC2 – pronounced trip-see-two – gene, which was later found to be essential for vomeronasal function.

The TRPC2 gene is an ion channel – a gateway in the cells of the vomeronasal organ that lets positively and negatively charged atoms called ions pass through the organ to the brain. Via electrical impulses, those ions carry information about pheromones to the brain.

Without that gene, the mice couldn't detect pheromones through the vomeronasal organ, research showed. Their behavior completely changed as a result.

"The male mice didn't show aggressive behavior toward the other male mice, as they had when they could detect pheromones," Liman said. "That was expected. What was not expected was that the male mice tried to mate with other male mice just as much as they did with females."

In humans, TRPC2 is what's called a pseudo-gene.

"A pseudo-gene is a gene that was once functional, but there's something the matter with the genetic sequence so it can no longer make a functional protein," Liman said.

"In our new study we were trying to understand where in evolution humans lost this gene. This was a way of telling us where we stopped using the vomeronasal organ."

Liman and Innan studied the primate DNA for mutations – permanent changes in the primates' hereditary material that meant they could not make the TRPC2 protein.

"Our inference is that if they don't have the TRPC2 gene, they don't have vomeronasal function," Liman said. "We found that mutations that might affect the functioning of the protein started to occur in the common ancestor of Old World monkeys, apes and humans about 40 million years ago."

That was a point in primate evolution when color vision was becoming better developed – an occurrence that may explain why primates started to rely more on their eyes than their noses for important behavioral cues from members of their own species, Liman said.

"I've hypothesized that visual cues have largely taken the place of pheromonal cues in these species," she said. "The fact that we can see where this happened, and that it fits in with all of the anatomical evidence, makes this study different.

"There's been a lot of speculation, but no one has taken a serious look at what was going on in humans and other primates. Our method was particularly powerful for looking at that."

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The findings will be published this week in an online edition of the Proceedings of the National Academy of Science. The research was funded by the National Institutes of Health.

To see the research article, go to http://www.pnas.org.


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