Interactions across biological networks are often quantified under a single set of conditions; however, cellular behaviors are dynamic and interactions can be expected to change in response to molecular context and environment. To determine the consistency of network interactions, we examined the enzyme network responsible for the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH across three different conditions: oxidative stress, starvation, and desiccation. Synthetic, activity-variant alleles were used in Drosophila melanogaster for glucose-6-phosphate dehydrogenase (G6pd), cytosolic isocitrate dehydrogenase (Idh), and cytosolic malic enzyme (Men) along with seven different genetic backgrounds to lend biological relevance to the data. The responses of the NADP-reducing enzymes and two downstream phenotypes (lipid and glycogen concentration) were compared between the control and stress conditions. In general, responses in NADP-reducing enzymes were greater under conditions of oxidative stress, likely due to an increased demand for NADPH. Interactions between the enzymes were altered by environmental stress in directions and magnitudes that are consistent with differential contributions of the different enzymes to the NADPH pool: the contributions of G6PD and IDH seem to be accentuated by oxidative stress, and MEN by starvation. Overall, we find that biological network interactions are strongly influenced by environmental conditions, underscoring the importance of examining networks as dynamic entities.
Transvection, a chromosome pairing-dependent form of trans-based gene regulation, is potentially widespread in the Drosophila melanogaster genome and varies across cell types and within tissues in D. melanogaster, characteristics of a complex trait. Here, we demonstrate that the trans-interactions at the Malic enzyme (Men) locus are, in fact, transvection as classically defined and are plastic with respect to both genetic background and environment. Using chromosomal inversions, we show that trans-interactions at the Men locus are eliminated by changes in chromosomal architecture that presumably disrupt somatic pairing. We further show that the magnitude of transvection at the Men locus is modified by both genetic background and environment (temperature), demonstrating that transvection is a plastic phenotype. Our results suggest that transvection effects in D. melanogaster are shaped by a dynamic interplay between environment and genetic background. Interestingly, we find that cis-based regulation of the Men gene is more robust to genetic background and environment than trans-based. Finally, we begin to uncover the nonlocal factors that may contribute to variation in transvection overall, implicating Abd-B in the regulation of Men in cis and in trans in an allele-specific and tissue-specific manner, driven by differences in expression of the two genes across genetic backgrounds and environmental conditions.
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