University researchers have discovered that females have an extraordinary ability to detect small genetic differences between males with their sense of smell, preferring the scent of men who are genetically similar, but not identical, to their fathers.

“We’ve just showed that humans have this capacity and preference. No one has shown this yet, even in animals,” said Martha K. McClintock, professor in the department of psychology and a co-author of the study.

The study, which appears in the February 2002 issue of Nature Genetics, found that paternally-inherited genes determine which male odors women find more pleasing. “You’d expect matches with smells that they grew up with, but that’s not the case,” McClintock said.

Preference lies in the human leukocyte antigen (HLA), a sequence in the human genome that distinguishes between the body’s cells and foreign cells. According to the study, conducted by University post-doctoral fellow Suma Jacob, the HLA sequences of men tended to match that of the fathers of the women who preferred their smell.

The work arose from a study by Carole Ober of the Department of Human Genetics, which found HLA similarities within married couples. Working on that basis, and considerable research on the relationship between smell and mating preference in animals, Jacob and McClintock devised a double-blind test to investigate whether odor and HLA similarities.

“You couldn’t see the genes and you couldn’t hear the genes,” said McClintock, “so we chose to investigate smell.”

Men selected for their genetic diversity wore t-shirts for two days, while avoiding smell-producing foods such as garlic and harsh odors like cigarette smoke. The shirts were then placed in boxes with a small hole so that the contents of the box could be smelled but not seen. The women were not told where the odors came from; they were simply asked to rate the smells based on the categories of familiarity, intensity, pleasantness and spiciness.

“It shows that the genetic predilection has to be inherited. Experience alone is not enough,” McClintock said.

The subjects preferred scents originating from donors whose HLA alleles matched those inherited paternally over non-inherited similarities. According to McClintock, this is a result of nature striking a balance.

“People understand why we would naturally avoid inbreeding, such as avoiding recessive genes,” said McClintock, adding that avoiding non-inherited similarities is “a way of minimizing the cost of outbreeding.”

McClintock describes “outbreeding” as the opposite of inbreeding, passing down too few genes from a given gene pool.

While the study focused on women’s reactions to men’s scents, McClintock believes–based in part on previous studies done on baboons and mice–that HLA detection may have implications beyond mating. The study mentions that female baboons are much more likely to dote on their paternal half-sisters than their maternal half-sisters. McClintock says that female mice, who raise their offspring collectively, choose their female co-parents based in part on major histocompatibility complex similarities.

“I’d like to look at women and women’s scents… because I think this is more broad than just mating. I think it may affect social interaction more generally,” McClintock said.

Jacob, who is now at UCLA, earned her B.A., Ph.D. and M.D. at the University; McClintock is a widely-recognized expert in the field of chemosignals.