Quantitative Genetic Analysis of Sleep inDrosophila melanogaster

Abstract

Although intensively studied, the biological purpose of sleep is not known. To identify candidate genes affecting sleep, we assayed 136 isogenic P-element insertion lines of Drosophila melanogaster. Since sleep has been negatively correlated with energy reserves across taxa, we measured energy stores (whole-body protein, glycogen, and triglycerides) in these lines as well. Twenty-one insertions with known effects on physiology, development, and behavior affect 24-hr sleep time. Thirty-two candidate insertions significantly impact energy stores. Mutational genetic correlations among sleep parameters revealed that the genetic basis of the transition between sleep and waking states in males and females may be different. Furthermore, sleep bout number can be decoupled from waking activity in males, but not in females. Significant genetic correlations are present between sleep phenotypes and glycogen stores in males, while sleep phenotypes are correlated with triglycerides in females. Differences observed in male and female sleep behavior in flies may therefore be related to sex-specific differences in metabolic needs. Sleep thus emerges as a complex trait that exhibits extensive pleiotropy and sex specificity. The large mutational target that we observed implicates genes functioning in a variety of biological processes, suggesting that sleep may serve a number of different functions rather than a single purpose.

Transcriptional Networks for Alcohol Sensitivity in Drosophila melanogaster

“…We did not observe significant sex differences (r ¼ 0.98, P , 0.0001; Figure S2). This lack of sexual dimorphism agrees with our previous study on alcohol sensitivity in 40 inbred wild-derived lines (Morozova et al 2009), but contrasts with other traits examined in these lines, including sleep (Harbison and Sehgal 2008), startle behavior , and olfactory avoidance behavior (Sambandan et al 2006), where significant differences in mutational effects between the sexes have been reported.…”

“…A total of 35% of the P-element insertion lines tested for aggression exhibited levels of aggression that differed significantly from the control (Edwards et al 2009b). Fifteen percent of P-element insertions with known effects on physiology, development, and behavior affect 24-hr sleep time (Harbison and Sehgal 2008). The numbers of abdominal and sternopleural bristles were affected by 38.3% of co-isogenic P-element insertions (Norga et al 2003).…”

“…This percentage demonstrates a large mutational target for alcohol sensitivity and indicates that a large fraction of the genome contributes to alcohol sensitivity, implicating extensive pleiotropy (Table S3). Indeed, most of the mutations that affect alcohol sensitivity have pleiotropic effects on other complex traits, including aggression (Edwards et al 2009b), life span (Magwire et al 2010), and sleep (Harbison and Sehgal 2008) (Table S3).…”

“…The group of lines with increased resistance to ethanol exposure also showed enrichment for the ''nervous system development'' category, but in addition was enriched for genes associated with imaginal disc, organ, tissue and sensory organ development, as well as cell motility and neurogenesis. Most of the mutations that affect alcohol sensitivity have pleiotropic effects on other complex traits, such as startle-induced locomotion , aggression (Edwards et al 2009b), sleep (Harbison and Sehgal 2008), and starvation stress resistance (Harbison et al 2005) (Table S3). We found significant positive correlations with aggression (N ¼ 43, r ¼ 0.35, P ¼ 0.012) (Edwards et al 2009b), lifespan (N ¼ 142, r ¼ 0.32, P , 0.0001) (Magwire et al 2010), and 24 hr sleep (N ¼ 22, r ¼ 0.52, P ¼ 0.008; Figure S1) (Harbison and Sehgal 2008).…”

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

“…These factors are sensed in and activate neurons that promote sleep or inhibit those that promote wake. To dissect the molecular basis of sleep homeostasis, a wide range of approaches has been used to identify pathways that contribute to sleep homeostasis, including unbiased forward genetic screens using chemical mutagens (Cirelli et al 2005a;Wu et al 2008) or transposable elements , RNA interference (RNAi), and the cloning of quantitative trait loci (Harbison and Sehgal 2008) as well as reverse or candidate genetics. In theory, a "homeostatic mutant" should impact the homeostatic response to sleep deprivation, typically evident as a change in the amount or intensity (e.g., SWA in vertebrates) during recovery sleep.…”