Conference Paper

Preliminary data from a functional screen reveals multiple sleep-regulating genes in A. mexicanus

Hutton, P., Rodríguez-Morales, R., Ferrufino, E., Lloyd, E., Dubuoé, E.R., Kowalko, J.E. and Keene, A.C.

Record Number:
5614
Year:
2022
Journal:
AIM 2022
Pages:
21
Abstract:
Sleep is a universally conserved behavior, yet animals vary strikingly in the timing and duration of its expression. A. mexicanus cave-dwelling populations sleep ~80% less than extant surface-dwelling populations, and previous transcriptomic studies reveal genes that differ between surface fish and cavefish in their rhythmic expression, or that respond differently to experimental sleep restriction. These provide strong sleep-regulating candidate genes, but we require functional genetic studies to confirm their role in the evolution of sleep loss in A. mexicanus. We have identified 19 candidate genes that are transcriptionally differentially regulated in response to sleep loss, and contain markers of selection. We are currently using CRISPR-Cas9 targeted mutagenesis in both surface fish and cavefish to determine whether these candidate genes impact sleep. Testing both populations allows for detection of both the loss of sleep-promoting gene function, or the gain of wake-promoting gene function, during the evolutionary transition from surface to cave environments. Sleep duration, bout length, and bout numbers are assayed in 6 dpf G0 larvae and compared to same-age and same-tank control larvae. With this approach, we have identified multiple genes likely involved in sleep regulation, some of which may represent genes underlying the evolution of sleep loss in Mexican cavefish. Given the deep phylogenetic conservation of sleep behavior and genetics, these results may help identify insomnia-associated genes in humans.
Times Cited:
1