David Stern wants to know how the fly genome behaves in the real world.

The tiniest hairs on fruit fly larvae have complex genetic controls that David Stern almost missed—until he took the fruit flies out of their cozy incubators.

The average fruit fly doesn’t live in a climate-controlled lab. Most must fend for themselves, seeking food, evading predators, and enduring chilly nights and hot days. These are the real-world conditions under which the insects have evolved, says HHMI investigator David Stern, and many of the marks that evolution has left on the fly’s genome will be difficult to decipher unless researchers consider those factors as they design their experiments.

It’s a lesson that Stern’s lab group underscored with its latest discovery about the genetic components that control the production of tiny hairs that poke from the surface of newly hatched fly larvae. The hairs, called trichomes, show up in roughly the same spot in most species of fruit flies, and Stern’s lab has solid evidence that evolution has made a point of keeping them around.

“It’s very clear from the evolutionary pattern that the flies care very much [about their trichomes],” he says. Biologists, on the other hand, have yet to figure out why they’re there. “We have a lot of stories about what the trichomes are for,” Stern says, “but they’re all just tall tales.”

Trichomes captured Stern’s attention with their deceptive simplicity: researchers had long known that when a gene called shavenbaby is missing in flies, they don’t make the trichomes; instead, they hatch out bald. Stern found that shavenbaby was more active in some species than in others, and the level of activity correlated with species-specific variations in trichome patterns. He set out to identify nearby DNA sequences that contributed to these variations.

“We started bashing away at it very naively, imagining that all we had to do was go one or two kilobases upstream from the promoter, find the single nucleotide change, and we’d be home by Christmas,” he remembers.

Ten years later, many of the microscopes in Stern’s lab are still focused on the larval trichomes. His group’s methodical search for regulators of shavenbaby has taken them far from the gene itself, and the story keeps getting more complicated. They’ve analyzed the DNA within 93,000 base pairs of shavenbaby and found six separate sections of DNA that promote the gene’s activity. Five of these enhancers have acquired sufficient mutations during evolution to produce new trichome patterns in various species.

Photo: Mark Mahaney

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