Genome-wide association study of sleep in Drosophila melanogaster

Abstract

BackgroundSleep is a highly conserved behavior, yet its duration and pattern vary extensively among species and between individuals within species. The genetic basis of natural variation in sleep remains unknown.ResultsWe used the Drosophila Genetic Reference Panel (DGRP) to perform a genome-wide association (GWA) study of sleep in D. melanogaster. We identified candidate single nucleotide polymorphisms (SNPs) associated with differences in the mean as well as the environmental sensitivity of sleep traits; these SNPs typically had sex-specific or sex-biased effects, and were generally located in non-coding regions. The majority of SNPs (80.3%) affecting sleep were at low frequency and had moderately large effects. Additive models incorporating multiple SNPs explained as much as 55% of the genetic variance for sleep in males and females. Many of these loci are known to interact physically and/or genetically, enabling us to place them in candidate genetic networks. We confirmed the role of seven novel loci on sleep using insertional mutagenesis and RNA interference.ConclusionsWe identified many SNPs in novel loci that are potentially associated with natural variation in sleep, as well as SNPs within genes previously known to affect Drosophila sleep. Several of the candidate genes have human homologues that were identified in studies of human sleep, suggesting that genes affecting variation in sleep are conserved across species. Our discovery of genetic variants that influence environmental sensitivity to sleep may have a wider application to all GWA studies, because individuals with highly plastic genotypes will not have consistent phenotypes.

Behavioral idiosyncrasy reveals genetic control of phenotypic variability

“…To test this possibility, we scored additional phenotypes from our Y-maze data, namely, the total number of turns (a measure of overall activity); the left-right mutual information between successive turns; and the regularity of turn timing. We also analyzed other phenotypes previously measured on the DGRP at the individual level [starvation resistance (19), chill coma recovery (19), startle response (19), and night sleep (20)]. We found significant genetic variation for variability in all these phenotypes, confirming that genetic control of variability is ubiquitous across phenotypes.…”

Effects of larval crowding on quantitative variation for development time and viability in Drosophila melanogaster

“…The DGRP strains are characterized by high genetic (Mackay et al., 2012; Massouras et al., 2012) and phenotypic variation (Ayroles et al., 2009; Durham, Magwire, Stone, & Leips, 2014; Ellis et al., 2014; Harbison, McCoy, & Mackay, 2013; Mackay et al., 2012; Unckless, Rottschaefer, & Lazzaro, 2015). Fly stocks were ordered from the Bloomington Stock Center and are kept in standard molasses/soy‐corn flour/agar media‐containing vials.…”

“…To test for rank‐order changes across the three densities, we subtracted line‐mean ordered genotype IDs for both DT and EAV, ranked them by using low‐density data as a reference, and calculated the Kendall's coefficient of concordance (Kendall's W ; Friedman, 1937). We also examined correlations between DT, EAV, and other traits that have been measured in the DGRP by other research groups (e.g., Ayroles et al., 2009; Durham et al., 2014; Ellis et al., 2014; Harbison et al., 2013; Unckless et al., 2015). All correlation coefficients reported in the results are Spearman's ρ.…”

Behavioral individuality reveals genetic control of phenotypic variability

“…We assesed 4 traits as measured in this study and 4 additional traits gathered from the literature (standard deviation for starvation, startle response, chillcoma recovery 3 , coefficient of environmental variation for night sleep 23 ). Phenotypic correlation between traits was computed as the pearson product-moment correlation.…”

“…To test this possibility, we scored additional phenotypes from our Y-maze data, namely, the total number of turns (a measure of overall activity); the mutual leftright information between successive turns; and the regularity of turn timing. We also analyzed other phenotypes previously measured on the DGRP (starvation resistance 22 , chill coma recovery 22 , startle response 22 , and night sleep 23 ). We found significant genetic variation for variability in all these phenotypes, confirming that genetic control of variability is ubiquitous across phenotypes.…”