612: Drunken flies and fish
Drunken flies and fish:
Scholz et al. screened mutagenized flies, looking for mutants that never learned to hold their liquor. They found one, called hangover (hang). Flies mutant for hangover have significantly reduced tolerance, and similar doses of alcohol knock them out over and over again. They have some capacity for tolerance, but it's greatly reduced. There is also a second molecular pathway, the octopaminergic pathway (octopamine is a neurotransmitter used in the fly's brain), and mutating that in addition reduces the animal's tolerance still further.
Why would animals have a gene to help them cope with alcohol? Alcohol exposure is ubiquitous in the environment, especially if you have to share your diet with yeast, which spew the stuff all over. The interesting thing, though, is that alcohol tolerance is coupled to an animal's general ability to handle stress, such as heat and oxidants. Flies with the hangover mutation are also more sensitive to heat shock and reactive oxygen species, and tend to have a shorter life span. It's more than just an alcohol tolerance gene—it's a general stressor response gene.
What makes this relevant to us in a utilitarian way is that our response to alcohol is a generic property of many animals: flies, fish, mice, and people can all get drunk and exhibit similar symptoms and cope with similar molecular mechanisms. It's universal!
In summary, the development of ethanol tolerance in Drosophila engages two systems that function in parallel, one involving a cellular stress pathway defined by the hang gene and the other involving octopaminergic systems. Octopamine has recently been implicated in the formation of appetitive (sugar-reinforced) memories in Drosophila. The contribution of learned behaviours and stress, at both the cellular and systemic levels, to drug- and addiction-related behaviours in mammals is being increasingly recognized. Our studies in Drosophila suggest that these pathways are conserved, allowing further analysis in this genetically tractable model organism.
And that's why I'm thinking of trying a few pilot experiments to get my fish drunk. There are tools and techniques out there that will allow us to probe the details of these processes in our experimental animal, and they are applicable to lots of other beasties as well…this evolution idea is the glue that brings many ideas together.
Ah, common descent.