Project description:A study evaluating the effect of stress resistance selection of Drosophila melanogaster. Abstract Here, we report a detailed analysis of changes in gene expression in Drosophila melanogaster selected for multiple eological relevant environmental stress resistance traits. We analyzed females from three biological replicates from seven selection regimes and one control regime using whole genome gene expression arrays. Replicated selection lines were selected for resistance to acute heat survival, high temperature knock down, constant 30°C during development, cold shock survival, desiccation and starvation, respectively. Additionally, a set of replicated lines was selected for increased longevity. When compared to gene expression profiles of control lines, we were able to detect consistent selection responses at the transcript level in each specific selection regime and also found a group of differentially expressed genes that were generally changed among all selected lines. Replicated selection lines clustered together, i.e. showed similar changes in gene expression (compared to controls) and thus showed that 10 generations of artificial selection gives a clear signal among gene expression profiles. The changes in gene expression in lines selected for increased longevity, desiccation and starvation resistance, respectively, showed high similarities. Cold resistance selected lines showed little differentiation from controls. Different methods of heat selection (heat survival, heat knock down and constant 30°C) showed little similarity verifying that different mechanism are involved in high temperature adaptation. The direction of change in gene expression in the selected lines showed a consistent pattern for each selection regime. For most selection regimes and in the comparison of all selected lines and controls exclusively up- or down regulation of gene expression among significant differentially expressed genes was found. The different responses to selection expressed in individual selection regimes and among all selected lines indicate that we have identified genes involved in stress specific and general stress response mechanisms. Keywords: control versus selected
Project description:Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. We performed artificial selection for alcohol sensitivity for 25 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. Keywords: artificial selection, whole genome expression profiling