Genetic basis of susceptibility to low-dose paraquat and variation between the sexes in Drosophila melanogaster.

Toxicant resistance is a complex trait, affected both by genetics and the environment. Like most complex traits, it can exhibit sexual dimorphism, yet sex is often overlooked as a factor in studies of toxicant resistance. Paraquat, one such toxicant, is a commonly used herbicide and is known to produce mitochondrial oxidative stress, decrease dopaminergic neurons and dopamine (DA) levels, and decrease motor ability. While the main effects of paraquat are well-characterized, less is known about the naturally occurring variation in paraquat susceptibility. The purpose of this study was to map the genes contributing to low-dose paraquat susceptibility in Drosophila melanogaster, and to determine if susceptibility differs between the sexes. One hundred of the Drosophila Genetic Reference Panel (DGRP) lines were scored for susceptibility via climbing ability and used in a genome-wide association study (GWAS). Variation in seventeen genes in females and thirty-five genes in males associated with paraquat susceptibility. Only two candidate genes overlapped between the sexes despite a significant positive correlation between male and female susceptibilities. Many associated polymorphisms had significant interactions with sex, with most having conditionally neutral effects. Conditional neutrality between the sexes probably stems from sex-biased expression which may result from partial resolution of sexual conflict. Candidate genes were verified with RNAi knockdowns, gene expression analyses, and DA quantification. Several of these genes are novel associations with paraquat susceptibility. This research highlights the importance of assessing both sexes when studying toxicant susceptibility.

Investigation of Drosophila fruitless neurons that express Dpr/DIP cell adhesion molecules.

Drosophila reproductive behaviors are directed by fruitless neurons. A reanalysis of genomic studies shows that genes encoding dpr and DIP immunoglobulin superfamily (IgSF) members are expressed in fru P1 neurons. We find that each fru P1 and dpr/DIP (fru P1 ∩ dpr/DIP) overlapping expression pattern is similar in both sexes, but there are dimorphisms in neuronal morphology and cell number. Behavioral studies of fru P1 ∩ dpr/DIP perturbation genotypes indicate that the mushroom body functions together with the lateral protocerebral complex to direct courtship behavior. A single-cell RNA-seq analysis of fru P1 neurons shows that many DIPs have high expression in a small set of neurons, whereas the dprs are often expressed in a larger set of neurons at intermediate levels, with a myriad of dpr/DIP expression combinations. Functionally, we find that perturbations of sex hierarchy genes and of DIP-ε change the sex-specific morphologies of fru P1 ∩ DIP-α neurons.

Effects of Dual Exposure to the Herbicides Atrazine and Paraquat on Adult Climbing Ability and Longevity in Drosophila melanogaster.

Anthropomorphic effects are changing the planet, and therefore, organisms are being exposed to many new biotic and abiotic stressors. Exposure to multiple stressors can affect organisms in ways that are different than the sum of their individual effects, and these interactions are often difficult to predict. Atrazine and paraquat are two of the most widely used herbicides in the United States, and are individually known to increase oxidative damage, affect dopaminergic functioning, reduce longevity, and alter motor ability in non-target organisms. We measured the effects of individual and combined exposure to low doses of atrazine and paraquat on climbing ability and longevity of Drosophila melanogaster. Atrazine and paraquat interact to affect D. melanogaster climbing ability and longevity in different ways. Atrazine appeared to have a weak mitigative effect against the decrease in climbing ability caused by paraquat. In contrast, combined exposure to atrazine and paraquat had detrimental synergistic effects on female longevity. Overall, this study shows that atrazine and paraquat can interact and that it is important to measure several traits when assessing the consequences of exposure to multiple stressors. Future studies should continue to assess the impacts of stressor interactions on organisms, as many combinations have never been examined.