Modulation of the Drosophila Transcriptome by Developmental Exposure to Alcohol

Prenatal exposure to ethanol can cause fetal alcohol spectrum disorder (FASD), a prevalent and preventable pediatric disorder. Identifying genetic risk alleles for FASD is impossible in human populations, but the Drosophila genetic model can provide insights. We analyzed changes in genome-wide gene expression in 96 wild-derived inbred fly lines after exposure to alcohol during development. We found extensive sexual dimorphism in the effect of alcohol on gene expression along with effects on adult locomotor activity and sleep. Genetic networks associated with changes in gene expression include both protein-coding and non-coding transcripts, including a female-specific module of small nucleolar RNAs that regulate pseudouridylation of ribosomal RNA. These data support a regulatory role for non-coding elements in response to developmental alcohol exposure. We selected 96 lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) across the range of phenotypic variation of effects of alcohol exposure on viability and developmental time (Dataset S1) and reared them on cornmeal-molasses-agar medium supplemented with10% (v/v) ethanol at 25°C, 60-75% relative humidity and a 12-hr light-dark cycle at equal larval densities. We collected two replicates of mated 3-5-day old flies (25 females and 30 males per line) for a total of 384 samples. These samples were sequenced using Illumina HiSeq and combined with previous RNASeq data on the same fly lines from Everett et al 2020 (10.1101/gr.257592.119) for a treatment vs baseline comparison.