ABSTRACT
Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.
Subject(s)
Drosophila melanogaster/genetics , Gene Regulatory Networks/genetics , Selection, Genetic , Signal Transduction/genetics , Sleep/genetics , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Gene Frequency , Intracellular Signaling Peptides and Proteins/metabolism , Male , Mitogen-Activated Protein Kinases/metabolism , Mutagenesis , Mutation , Phenotype , Polymorphism, Genetic , Protein Serine-Threonine Kinases/metabolism , Receptors, Invertebrate Peptide/genetics , Receptors, Invertebrate Peptide/metabolism , Time Factors , Whole Genome Sequencing , Wnt1 Protein/genetics , Wnt1 Protein/metabolismABSTRACT
Ovariole number has a direct role in the number of eggs produced by an insect, suggesting that it is a key morphological fitness trait. Many studies have documented the variability of ovariole number and its relationship to other fitness and life-history traits in natural populations of Drosophila However, the genes contributing to this variability are largely unknown. Here, we conducted a genome-wide association study of ovariole number in a natural population of flies. Using mutations and RNAi-mediated knockdown, we confirmed the effects of 24 candidate genes on ovariole number, including a novel gene, anneboleyn (formerly CG32000), that impacts both ovariole morphology and numbers of offspring produced. We also identified pleiotropic genes between ovariole number traits and sleep and activity behavior. While few polymorphisms overlapped between sleep parameters and ovariole number, 39 candidate genes were nevertheless in common. We verified the effects of seven genes on both ovariole number and sleep: bin3, blot, CG42389, kirre, slim, VAChT, and zfh1 Linkage disequilibrium among the polymorphisms in these common genes was low, suggesting that these polymorphisms may evolve independently.
