Brown researchers uncover the underlying genetics that make flies champion fliers

A complex network of wing, muscle and nervous system genes all contribute to flight performance, a new PLOS Genetics study shows.

PROVIDENCE, R.I. [Brown University] — Flies have evolved excellent flying skills thanks to a set of complicated interactions between numerous genes that influence wing shape, muscle function and nervous system development, as well as the regulation of gene expression during development. These interactions are identified by a team of Brown University researchers in a Thursday, March 18, PLOS Genetics study.

high performance flies
Fruit flies in the flight performance assay work to control their descent after an abrupt drop into a flight column.

“Fruit flies are colloquially named after their most recognizable ability: flight,” said study lead author Adam Spierer. “Yet until now, there wasn’t a systematic study working to uncover the genetics of flight in flies with modern genetic and computational tools.”

Spierer, a post-doctoral researcher who earned his Ph.D. from Brown in 2020, conducted the research while working in the lab of David M. Rand, a professor of ecology and evolutionary biology and study co-author.

“One of the big questions in biology asks: How does genotype, or DNA, contribute to phenotype, or the traits we possess?” Spierer said. “Previously, it was thought that the summation of effects from many genes can add up to the end result. But other studies have done a good job of showing specific combinations of variants and genes can also have a large impact. Our work supports the role of both types of effects and interactions, and contributes to the broader debate within the field of quantitative genetics and complex traits.”

The familiar airborne insects of the genus Drosophila rely on flight for vital tasks, like courtship, finding food and dispersing to new areas. Despite the importance of this ability, scientists have known little about the genetics underlying flight performance.

In the new study, the research team performed an analysis, called a genome-wide association study, to identify genes associated with flight. Using 197 genetically different fruit fly lines, they tested the flies’ ability to pull out of a sudden drop. Then, using multiple computational approaches (including the new PEGASUS_flies, a gene inference tool first used in human studies that this research team adapted for Drosophila), they related the flies’ performance to different genes and genetic variants, as well as to networks of gene-gene and protein-protein interactions.

Natural born fliers


In response to an abrupt drop, "stronger" fliers/genotypes were able to quickly and effectively right themselves and control their descent.

The researchers discovered that many genes and genetic variants involved in flight performance mapped to regions of the fly genome that determine wing shape, muscle and nervous system function, and regulate whether other genes are turned on or off.

They also identified a gene called pickpocket 23 (ppk23) that serves as a central hub for regulating the interactions of these genes. Pickpocket family genes are involved in proprioception — self-awareness of body position and movement — and in detecting pheromones and other chemical signals.

“This study suggests the pickpocket gene plays a more central role in flight performance than previously expected,” Spierer said.

The team’s snapshot of the genetic variants that affect fruit fly flight performance may have implications for studying flight in other insects, and provide novel insights into the feedback systems that regulate flight control.

The research demonstrates the benefit of using multiple approaches to unravel the complex genetic interactions underlying traits like flight, which involve a number of different genes.

Weaker aviators


"Weaker" fliers/genotypes were less successful in controlling their descent after an abrupt drop.

“While the study focuses on flight performance, the approaches used here provide a model for how to use multiple genetic and computational approaches to understand complex traits,” Rand said.

Adds Spierer: “Flies are a great model organism because of their cellular crossover with other organisms, and because of the many great genetic and computational resources available. While we can't necessarily make a 1:1 crossover between fruit flies and other insects, we can come close enough to provide hints and leads for researchers working on similar studies with other insects that aren’t as accessible.”

Computational analyses were developed and performed by Jim Mossman, a former postdoctoral research associate in the Rand lab; Sohini Ramachandran, an associate professor of biology and director of the Center for Computational Molecular Biology at Brown; Lorin Crawford, an assistant professor of biostatistics; and Sam Smith, a graduate student in Ramachandran’s lab.

“The study is a great example of the collaborative nature of Brown's departments and centers that facilitate integrative research,” Rand said.

The researchers were supported by the National Institutes of Health, the Dana Farber Cancer Institute, an Alfred P. Sloan Research Fellowship, a Packard Fellowship for Science and Engineering, and a National Science Foundation CAREER Award.