ANDRZEJ KRAUZEIn the wild, male animals typically compete with each other for the attention of the opposite sex. When the female of a species—mouse, rat, cat, dog, or human—puts the lion’s (or rather, lioness’s) share of effort into raising offspring, she becomes a shrewd investor who must be choosy about her mate. Evolutionary biologist Jane Hurst at the University of Liverpool has found that male mice have evolved a cunning trick to distinguish themselves within the dating pool: they produce a specific protein that drives female attraction to male scent, and this molecule, called darcin, helps females remember a specific male’s odor.
Hurst studies how animals use scent cues to recognize different individuals and how they choose among potential mates in the wild. Scientists know more about scent cues in mice than in any other species of mammal. But laboratory mice, being confined to cages in controlled environments, don’t go looking for mates. As Hurst observed wild mice, it became obvious to her that she was missing something. She could see the mice sniffing their surroundings and each other, and she yearned to understand more about the information they were gathering.
Male mice mark virtually every surface in their territory with urine. Because the scent chemicals in urine are volatile, and are specific to each individual, mice have to keep refreshing the marks—and they’ll also cover up the marks made by competing males in their territory. Hurst’s team, in collaboration with Robert Beynon, also at Liverpool, tested the ability of different chemical components of wild-mouse urine to keep female mice interested. Instead of seeing patterns of attraction to specific scents from certain mice, they found that the presence of a single, genetically invariant protein in the urine of male mice was necessary to attract female mice and to help them remember an individual male’s smell. If darcin was missing from urine, wild female mice were not attracted to male scent at all. On the other hand, recombinant darcin alone stimulated attraction in female mice. It is, Hurst says, “one of the only clear-cut cases of a mammalian pheromone.”
But darcin itself isn’t volatile, and it has no scent of its own. When a mouse sniffs, molecules flow into its nose, where the vomeronasal organ (VNO) has receptors for major urinary proteins. Darcin is likely to be detected there, where it stimulates an innate response—sexual attraction—that becomes associated with specific scent molecules.
Etienne Joly of IPBS, CNRS-University of Toulouse describes darcin as an “on/off switch” that is also important for kin recognition—making sure females are not attracted to closely related males. Interestingly, darcin appears to act without involving major histocompatibility complex (MHC) molecules, which were previously considered to be the driving force behind scent recognition and kinship selection/avoidance. Laboratory mice are not genetically diverse, and have little variation in their urinary proteins. Some common experimental strains have even lost darcin altogether, and Hurst thinks that in those strains MHC molecules take over mate selection and kin avoidance. But in the wild, darcin and urinary proteins are important. “The crunch came when they decided to go and catch mice in the wild,” Joly says. “That was the critical thing.” Hurst agrees, saying that her lab would never have discovered darcin if they had only used laboratory mice.
But immunogeneticist Andreas Ziegler of the Freie Universität Berlin urges caution. “It is unwise to relegate the MHC to a minor role,” he says. Joly agrees that the MHC remains important, but contends that “it’s in the passenger seat; it’s not in the driver’s seat.” Indeed, humans and great apes appear not to have a functional VNOs, and maybe their absence has made the MHC more important in humans and great apes. Ziegler says that extrapolating this work to humans would be “unwise,” and Joly says that researchers must now confirm which animals, humans included, actually do express darcin or an ortholog.
One thing that is certain is that darcin has a peculiar name. There is no established nomenclature for urinary proteins, and, because it has a specific function, Hurst wanted to call it something meaningful. At a dinner party, Beynon, Hurst’s husband, suggested naming it after Jane Austen’s character Fitzwilliam Darcy in Pride and Prejudice. Hurst admits to being a big fan of Jane Austen, and in particular of the BBC’s 1995 television version, in which Darcy is played by the English actor Colin Firth. “I’m afraid it just appealed to all of us,” Hurst says.
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