Evolutionary medicine leverages the power of naturally occurring phenotypic differences to investigate genetic mechanisms underlying diseases, including neurological and metabolic disorders. The Mexican cavefish exhibits a dramatic evolution of sleep loss, hyperphagia, and obesity compared to a surface fish of the same species, thus, providing a unique and powerful model for identifying genetic factors regulating these traits. The proposed experiments will implement genomic and transgenic technology in Mexican cavefish to identify genetic loci that contribute to sleep, feeding, and metabolism. In addition, these experiments have potential to identify whether shared genetic architecture underlies changes in these traits, providing insight into the relationship between sleep loss and metabolic disorders. Specifically, the contribution of cave-associated alleles in Hypocretin receptor 2 to sleep, feeding, and adiposity within a surface fish genetic background will be investigated. Beyond the immediate scientific goals, transgenic and genomic tools and techniques will be established and will provide a valuable resource and can be applied to address questions beyond the scope in this proposal, including in investigations of eye-degeneration and autism.

Public Health Relevance

Sleep and metabolic disorders present an enormous health burden throughout the world. This proposal will employ novel genomic and transgenic technology to investigate the genetic basis of these traits in a unique, emerging model fish system. Functional investigation of the genes and neural circuits regulating sleep loss will help illuminate the interaction between insomnia, obesity, and metabolic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM127872-03
Application #
9923710
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2018-05-15
Project End
2022-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Lloyd, Evan; Olive, Courtney; Stahl, Bethany A et al. (2018) Evolutionary shift towards lateral line dependent prey capture behavior in the blind Mexican cavefish. Dev Biol 441:328-337
Passow, Courtney N; Kono, Thomas J Y; Stahl, Bethany A et al. (2018) Nonrandom RNAseq gene expression associated with RNAlater and flash freezing storage methods. Mol Ecol Resour :
Chin, Jacqueline S R; Gassant, Claude E; Amaral, Paloma M et al. (2018) Convergence on reduced stress behavior in the Mexican blind cavefish. Dev Biol 441:319-327
Keene, Alex C; Duboue, Erik R (2018) The origins and evolution of sleep. J Exp Biol 221:
Herman, Adam; Brandvain, Yaniv; Weagley, James et al. (2018) The role of gene flow in rapid and repeated evolution of cave-related traits in Mexican tetra, Astyanax mexicanus. Mol Ecol 27:4397-4416