To make healthy sperm, mice must have genes that are well known for a completely different purpose: enabling the sense of taste. It's not as surprising as you might think. Over the past decade biologists have found taste and smell receptors—initially thought to be confined to the mouth and nose—in the brain, the gut, the kidneys and elsewhere throughout the body. What they are doing in all these places is still something of a puzzle, as the sperm study, published in July in the Proceedings of the National Academy of Sciences USA, shows.
The serendipitous finding emerged from an experiment that began a few years ago, when Bedrich Mosinger, a taste researcher at the Monell Chemical Senses Center in Philadelphia, was trying to breed mice missing two proteins involved in sensing sweet and umami (savory) flavors. He crossed parents that were each missing one of the proteins, expecting that at least some of the offspring would be missing both. In litter after litter, not a single such mouse was born.
Mystified, Mosinger and his colleagues traced the problem to the male mice by showing that females could pass on genetic material missing the sensory proteins, whereas males could not. “It was very strange and very striking,” he says. To explore how the taste-related genes act on sperm, the researchers engineered mice that were missing the gene for one protein, then fed the males a drug that switched off the second gene. Finally, they looked at the animals' sperm—and what they saw was a mess. The sperm heads were bent and often too large, and the tails were twisted over on themselves. By silencing those two taste genes, the researchers had somehow mangled the sperm-making machinery.
Sperm have been shown to host bitter-taste receptors and smell receptors, which most likely sense chemicals released by the egg. But the idea that such proteins might function in sperm development is new, says Yehuda Ben-Shahar of Washington University in St. Louis. In the other cells and organs where taste and smell receptors have been found, usually “the cells mature, and then these things kick in to interact with the environment,” he says. “This is the earliest that these types of genes have been implicated in the biological system that I know of.”
It is still a mystery how exactly the two genes control sperm development. Elsewhere in the body, researchers have found taste and smell receptors that help to sense toxins, pick up messages from gut bacteria or foil pathogens. At a meeting earlier this year of the Association for Chemoreception Sciences, Ben-Shahar even hosted a symposium entirely devoted to sensory receptors that crop up in unexpected places.
The proliferation of recent discoveries serves as a reminder that a whole world of alternative uses may be out there, even for genes that biologists are sure they have pegged. “When we assign functions to genes, it's a very narrow view of biology,” Ben-Shahar says. “Probably for every molecule that we assign a specific function to, if you look hard enough you'll find that it's doing other things in other contexts.