Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep

PLoS Genet. 2017 Dec 14;13(12):e1007098. doi: 10.1371/journal.pgen.1007098. eCollection 2017 Dec.

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.

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Gene Frequency
  • Gene Regulatory Networks / genetics*
  • 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
  • Selection, Genetic*
  • Signal Transduction / genetics*
  • Sleep / genetics*
  • Time Factors
  • Whole Genome Sequencing
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Invertebrate Peptide
  • Wnt1 Protein
  • wg protein, Drosophila
  • Egfr protein, Drosophila
  • ErbB Receptors
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila
  • Mitogen-Activated Protein Kinases

Grants and funding

This research was supported by the Intramural Research Program of the NIH, The National Heart Lung and Blood Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.