A host of genes work together to make some fruit flies into aerial acrobats while others remain weaker fliers, demonstrating how different genes interact to give rise to complex traits.

The researchers, whose findings were published March 18 in PLOS Genetics, found that differences in flying prowess among the insects they examined were likely related to genes and gene variants involved in the development of the nervous system, wings and muscles, and in controlling whether other genes are switched on or off.

"How it puts the machinery for flying together during its development is probably an important part of [whether] a fly will end up being able to fly well," said David Rand, chair of the department of ecology and evolutionary biology at Brown University and last author of the study. "It's how these individual mutations regulate the expression of genes during development that probably sets the stage for being a good or a bad flier."

An insect's ability to maneuver on the wing is central to finding food and mates and evading predators. This complex and vital skill depends on a number of other traits. 

"A lot of the genes that are important for growing wings or muscles or nerves are well known, but within every individual there's a lot of genes that will work together to make these things happen to a better or worse extent," said Adam Spierer, a postdoctoral researcher in the same department at Brown and first author of the study. "The genes that we were focused on were those that can turn the dial on that just a little bit." 

To measure flight performance, the researchers dropped vials of flies down a small shaft. When these little "elevators" hit the bottom, they dumped the flies into a meter-long tube. 

"As the flies were free-falling they would try to right themselves," Spierer said. "If they were weaker flies, it would take them longer to right themselves or to generate the lift to get them going." 

The stronger fliers landed at higher positions on the sides of the tube, while weaker ones tumbled and nosedived before finally regaining control and landing farther down.

The researchers then used a technique called a genome-wide association study to search for genetic differences that might explain why some of the insects were clumsier than others. They identified numerous genes, variations within genes and interactions between different genes related to wing development and other processes that may all contribute to an insect's flight skills. 

Particularly intriguing was a gene nicknamed "pickpocket 23." 

"Pickpocket 23 is a central node in this network of interacting genes," Rand said. It is known to be involved in the insects' ability to detect pheromones from prospective mates, as well as proprioception, the sense of one's position in space. The findings indicate that pickpocket 23 has a more important role in flying ability than has previously been recognized. 

The patterns that Rand, Spierer and their team uncovered are likely to shape processes that unfold while an insect is still an egg, larva or pupa. 

"We didn't find any significant association between gene expression in the adults and how that might have impacted their flight performance," Spierer said. "So that would tell us that a lot of the variation happening is at a much earlier stage in the fly's life cycle."

Some of these genes determine the shape and size of the wings and how the veins within them are spaced, or guide the development of sensory neurons and neurons that relay signals to the insect's muscles directing them to flap and control the angle of the wing. 

"Then the wings and the muscles have to come together and have to be coordinated in such a way that we get the better or worse flight performance," Spierer said.

It's possible that the genetic differences the team uncovered are the same ones that would make one fruit fly buzzing through a kitchen more difficult to swat than its neighbors, he says. However, the researchers only examined fruit flies belonging to a small population bred for scientific purposes, so it's not yet clear how well the findings will translate to wild fruit flies.

Although insect flight isn't directly related to human health, Rand also sees potential implications for research on conditions such as heart disease and high blood pressure. 

"It's a good example of how to take apart a trait that varies continuously in nature," he said. "This approach would be helpful for similar studies that go on in humans."

The study, "Natural variation in the regulation of neurodevelopmental genes modifies flight performance in Drosophila," published March 18 in PLOS Genetics, was authored by Adam N. Spierer, Jim A. Mossman, Samuel Pattillo Smith, Sohini Ramachandran and David M. Rand, Brown University; and Lorin Crawford, Brown University and Microsoft Research New England.