Quantitative genetic analysis of sleep in Drosophila melanogaster

Howard Hughes Medical Institute, Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Genetics (Impact Factor: 4.87). 05/2008; 178(4):2341-60. DOI: 10.1534/genetics.107.081232
Source: PubMed

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.

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Available from: Susan T Harbison, Oct 07, 2014
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    • "A P-element insertional mutagenesis screen for alcohol sensitivity revealed that almost 30 % of the P-element insertions tested affected the trait, indicating that a large fraction of the genome contributes to alcohol sensitivity and predicting extensive pleiotropy (Morozova et al. 2011; Fig. 2). Indeed, most of the mutations that affect alcohol sensitivity in Drosophila have pleiotropic effects on other complex traits (Harbison and Sehgal 2008; edwards et al. 2009; Magwire et al. 2010). "
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    ABSTRACT: Alcohol abuse and alcoholism incur a heavy socioeconomic cost in many countries. Both genetic and environmental factors contribute to variation in the inebriating effects of alcohol and alcohol addiction among individuals within and across populations. From a genetics perspective, alcohol sensitivity is a quantitative trait determined by the cumulative effects of multiple segregating genes and their interactions with the environment. This review summarizes insights from model organisms as well as human populations that represent our current understanding of the genetic and genomic underpinnings that govern alcohol metabolism and the sedative and addictive effects of alcohol on the nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s00438-013-0808-y) contains supplementary material, which is available to authorized users.
    MGG Molecular & General Genetics 01/2014; 289(3). DOI:10.1007/s00438-013-0808-y · 2.83 Impact Factor
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    • ", 2011 ) . Previously a P - element insertion allele at Crc ( Crc BG02566 ) was found to affect sleep phenotypes ( Harbison & Sehgal , 2008 ) , but this insertion was at a different site than the P - element insertion allele ( Crc BG01724 ) previously im - plicated in startle behaviour ( Yamamoto et al . , 2009 ) . "
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    ABSTRACT: Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insertions in Semaphorin-5C (Sema-5c) and Calreticulin (Crc), pleiotropic genes that affect olfactory behaviour and startle behaviour and, in the case of Crc, sleep phenotypes. We introduced Canton-S B (CSB) third chromosomes with or without a P-element insertion at the Crc or Sema-5c locus in multiple wild-derived inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and assessed the effects of epistasis on the olfactory response to benzaldehyde and, for Crc, also on sleep. In each case, we found substantial epistasis and significant variation in the magnitude of epistasis. The predominant direction of epistatic effects was to suppress the mutant phenotype. These observations support a previous study on startle behaviour using the same D. melanogaster chromosome substitution lines, which concluded that suppressing epistasis may buffer the effects of new mutations. However, epistatic effects are not correlated among the different phenotypes. Thus, suppressing epistasis appears to be a pervasive general feature of natural populations to protect against the effects of new mutations, but different epistatic interactions modulate different phenotypes affected by mutations at the same pleiotropic gene.
    Genetics Research 02/2012; 94(1):9-20. DOI:10.1017/S001667231200002X · 2.20 Impact Factor
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    • "Together, the strong effects of these mutations point toward membrane excitability as a key process in sleep. As in other areas of biology, the expectation is that mutant screens will continue to generate enough biological raw material for at least a generation of researchers in the field (Harbison and Sehgal 2008 and see Gondo et al. 2011). The powerful targeted spatial and temporal expression technologies of Drosophila have identified a few specific brain regions or neurons in which molecules or pathways of interest can act. "
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    ABSTRACT: The fruitfly Drosophila offers a model system in which powerful genetic tools can be applied to understanding the neurobiological bases of a range of complex behaviors. The Drosophila and human lineages diverged several hundred million years ago, and despite their obvious differences, flies and humans share many fundamental cellular and neurobiological processes. The similarities include fundamental mechanisms of neuronal signaling, a conserved underlying brain architecture and the main classes of neurotransmitter system. Drosophila also have a sophisticated behavioral repertoire that includes extensive abilities to adapt to experience and other circumstances, and is therefore susceptible to the same kinds of insults that can cause neuropsychiatric disorders in humans. Given the different physiologies, lifestyles, and cognitive abilities of flies and humans, many higher order behavioral features of the human disorders cannot be modeled readily in flies. However, an increasing understanding of the genetics of human neuropsychiatric disorders is suggesting parallels with underlying neurobiological mechanisms in flies, thus providing important insights into the possible mechanisms of these poorly understood disorders.
    01/2011; 7(1):37-60. DOI:10.1007/7854_2010_110
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