title: Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep.
abstract: Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes. Studies in Drosophila have revealed molecular pathways and neural tissues regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression to identify candidate genes. We independently confirmed that molecular polymorphisms in Catsup (Catecholamines up) are associated with variation in sleep and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways.
authors.affiliation: Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Harbison
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Carbone
authors.forename: Julien F
authors.initials: JF
authors.lastname: Ayroles
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lyman
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017849:Animals, Inbred Strains; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D017344:Genes, Insect; D014644:Genetic Variation / Q000502:physiology*; D049750:Genome, Insect; D055106:Genome-Wide Association Study / Q000662:veterinary; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012890:Sleep / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C511455:catsup protein, Drosophila