Genome-wide association in Drosophila identifies a role for Piezo and Proc-R in sleep latency.

Sleep latency, the amount of time that it takes an individual to fall asleep, is a key indicator of sleep need. Sleep latency varies considerably both among and within species and is heritable, but lacks a comprehensive description of its underlying genetic network. Here we conduct a genome-wide association study of sleep latency. Using previously collected sleep and activity data on a wild-derived population of flies, we calculate sleep latency, confirming significant, heritable genetic variation for this complex trait. We identify 520 polymorphisms in 248 genes contributing to variability in sleep latency. Tests of mutations in 23 candidate genes and additional putative pan-neuronal knockdown of 9 of them implicated CG44153, Piezo, Proc-R and Rbp6 in sleep latency. Two large-effect mutations in the genes Proc-R and Piezo were further confirmed via genetic rescue. This work greatly enhances our understanding of the genetic factors that influence variation in sleep latency.

Identification of Genes Contributing to a Long Circadian Period in Drosophila Melanogaster.

The endogenous circadian period of animals and humans is typically very close to 24 h. Individuals with much longer circadian periods have been observed, however, and in the case of humans, these deviations have health implications. Previously, we observed a line of Drosophila with a very long average period of 31.3 h for locomotor activity behavior. Preliminary mapping indicated that the long period did not map to known canonical clock genes but instead mapped to multiple chromosomes. Using RNA-Seq, we surveyed the whole transcriptome of fly heads from this line across time and compared it with a wild-type control. A three-way generalized linear model revealed that approximately two-thirds of the genes were expressed differentially among the two genotypes, while only one quarter of the genes varied across time. Using these results, we applied algorithms to search for genes that oscillated over 24 h, identifying genes not previously known to cycle. We identified 166 differentially expressed genes that overlapped with a previous Genome-wide Association Study (GWAS) of circadian behavior, strongly implicating them in the long-period phenotype. We tested mutations in 45 of these genes for their effect on the circadian period. Mutations in Alk, alph, CG10089, CG42540, CG6034, Kairos (CG6123), CG8768, klg, Lar, sick, and tinc had significant effects on the circadian period, with seven of these mutations increasing the circadian period of locomotor activity behavior. Genetic rescue of mutant Kairos restored the circadian period to wild-type levels, suggesting it has a critical role in determining period length in constant darkness.