Genetic networks underlying natural variation in basal and induced activity levels inDrosophila melanogaster

Abstract

Exercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual’s inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model system Drosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel 2 fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels in D. melanogaster and provides a resource for exercise biologists.

Drosophila melanogaster, a new model for exercise research

“…There are genes that impact activity levels in only one sex, and genes affecting both sexes, which now can be investigated in follow‐up studies utilizing the various Drosophila mutant collections available. This study demonstrates the complex contributions of genetics to exercise response and illustrates the immense potential for Drosophila to contribute to exercise research . Several different populations for GWAS can be obtained from the community, and tools and established protocols are readily available to investigate exercise response rates such as body composition, physical fitness, cardiac health, metabolites, memory/learning and more .…”

“…Dropping the enclosures results in the animals being knocked to the bottom of the enclosure, and due to their negative geotaxis response, they will attempt to climb to the top of the enclosure until they are dropped again . The Power Tower is a relatively intense form of exercise, and to induce a more gentle form of exercise, other groups have used partial (Swing Boat) or full rotations (Treadwheel, Rotating Exercise Quantification System [REQS], system developed by the Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province at Hunan Normal University in China) of the animal enclosures to induce exercise. When the animal enclosures are rotated, the orientation of “up” changes, and the animals are stimulated to continue to move, leading to exercise compared to control flies.…”

“…During the last several years, my research group has taken a different approach to harnessing the power of Drosophila genetics to answer questions in the field of exercise genetics. We have used Drosophila to carry out genome‐wide association studies (GWASs) investigating the animals’ baseline activity levels, as well as their induced activity levels during an exercise treatment with the goal of understanding the genetic architecture underlying exercise response traits . This study, which utilized the DGRP2 strain collection identified over 100 candidate genes involved in controlling the animals' activity levels.…”

“…We have used Drosophila to carry out genome-wide association studies (GWASs) investigating the animals' baseline activity levels, as well as their induced activity levels during an exercise treatment with the goal of understanding the genetic architecture underlying exercise response traits. 7 This study, which utilized the DGRP2 strain collection identified over 100 candidate genes involved in controlling the animals' activity levels. These candidate genes include genes with known impacts on animal activity, but also new genes not previously linked to animal activity.…”

“…This study demonstrates the complex contributions of genetics to exercise response and illustrates the immense potential for Drosophila to contribute to exercise research. 7 Several different populations for GWAS can be obtained from the community, and tools and established protocols are readily available to investigate exercise response rates such as body composition, physical fitness, cardiac health, metabolites, memory/learning and more. 1 Combining the Drosophila tools to assay exercise and exercise responses with the tools to carry out GWAS provides an untapped treasure trove for researchers interested in exploring the impact of genetic background on exercise related traits or identifying new pathways impacting exercise response.…”