Bar flies: fruit flies help unravel the genetics of alcohol sensitivity

Fruit flies are a useful model for investigating the contribution genes make to human alcohol sensitivity because, like humans, fruit flies can get 'drunk' if exposed to high levels of alcohol. Similar to many of us after a tipple or two, the intoxicated flies show movement problems, loss of postural control, and sleepiness; they also develop alcohol tolerance after repeated exposure to alcohol.

The research team, comprising Tatiana Morozova, Richard Anholt and Trudy Mackay,at the North Carolina State University, USA identified a number of genes in the fruit fly that appear to be associated with alcohol sensitivity. Interestingly, 23 of these genes have human equivalents (orthologs), which the authors suggest could be linked to alcohol sensitivity in people.

“We can now translate these findings from Drosophila to the human population by asking whether any of the 23 human orthologs are indeed associated with alcohol sensitivity – either drinking behaviour or addiction – in the human population,” says Professor Trudy Mackay.

The researchers bred fruit flies for over 25 generations to produce two distinct groups – flies that were highly sensitive to alcohol, and flies that were highly resistant to alcohol.

They then performed whole-genome transcript expression analysis to see how the genetic make-up of these flies had changed from the original base population. This technique allows all genes in the fruit fly to be examined in parallel, whereas earlier studies usually focused on particular individual genes.

Genes that are differentially expressed between the alcohol-resistant and alcohol-sensitive flies are candidate genes for alcohol sensitivity. Over 1000 such genes were identified in this study.

To explore if some of the differentially expressed genes were causally linked to alcohol sensitivity, the researchers looked at mutated versions of the genes. Tests of 35 mutated genes revealed 32 that directly affected sensitivity to alcohol; three of these genes had previously been associated by the research team with alcohol sensitivity or tolerance.

This further study by Mackay and colleagues may provide clues to the genetic basis of alcohol related issues in humans.