Genetics and genomics of alcohol responses in Drosophila

Abstract

Drosophila melanogaster has become a significant model organism for alcohol research. In flies, a rich variety of behaviors can be leveraged for identifying genes affecting alcohol responses and adaptations. Furthermore, almost all genes can be easily genetically manipulated. Despite the great evolutionary distance between flies and mammals, many of the same genes have been implicated in strikingly similar alcohol-induced behaviors. A major problem in medical research today is that it is difficult to extrapolate from any single model system to humans. Strong evolutionary conservation of a mechanistic response between distantly related organisms, such as flies and mammals, is a powerful predictor that conservation will continue all the way to humans. This review describes the state of the Drosophila alcohol research field. It describes common alcohol behavioral assays, the independent origins of resistance and tolerance, the results of classical genetic screens and candidate gene analysis, and the outcomes of recent genomics studies employing GWAS, transcriptome, miRNA, and genome-wide histone acetylation surveys.

The role of neuroimmune signaling in alcoholism

“…Activation of TLRs by endogenous DAMPs has been implicated in several non-infectious neurological disorders, including alcoholism (Table 1). Transcriptome analyses in Drosophila have implicated Toll genes in the alcohol response, as discussed by Park et al in their review in this special edition (Park et al, 2017). The expression of several TLRs are upregulated in the brains of human alcoholics.…”

Alcohol Increases Aggression in Flies

“…To help bridge this gap in knowledge, we introduce Drosophila melanogaster as a model organism in which male flies become more aggressive with exposure to alcohol. There exists a substantial body of work on the effects of alcohol on fly behavior as well as a considerable amount of work on aggression in flies (2,3). However, nothing is known about the intersection between these topics, that is, whether or not alcohol modulates aggression in flies.…”

Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance

“…H4 acetylation was modified at a large number of genomic loci 6 and 24 hours after ethanol exposure. 33 Further, the increase in histone acetylation can be quite rapid, starting during inebriation. 5 Therefore, acute ethanol induces genomic changes rapidly, broadly, and lastingly.…”

“…Scale bars: 10 μm H4 acetylation was modified at a large number of genomic loci 6 and 24 hours after ethanol exposure 33. The double mutants showed restored ethanol tolerance, compared to either mutant alone (Figure 4D).…”