Changes in neuronal signaling and cell stress response pathways are associated with a multigenic response of Drosophila melanogaster to DDT selection

Authors: SEONG, KEON MOOK - Michigan State University; Coates, Brad; SUN, WEILIN - Michigan State University; CLARK, JOHN - University Of Maryland; PITTENDRIGH, BARRY - Michigan State University

Submitted to: Genome Biology and Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/30/2017
Publication Date: 12/1/2017
Citation: Seong, K.M., Coates, B.S., Sun, W., Clark, J.M., Pittendrigh, B.R. 2017. Changes in neuronal signaling and cell stress response pathways are associated with a multigenic response of Drosophila melanogaster to DDT selection. Genome Biology and Evolution. 9(12):3356-3372. https://doi.org/10.1093/gbe/evx252.
DOI: https://doi.org/10.1093/gbe/evx252

Interpretive Summary: The evolution of resistance to chemical insecticides by insect populations result in reduced levels of control achieved by crop and livestock producers, and leads to lower output and profitability. In the current study, an ARS researcher along with university collaborators used a strain of a model insect species (fruitfly) to investigate the genomic basis of high resistance to DDT insecticides. The study used full genome re-sequencing and gene expression data, which indicated many different genome regions and differentially expressed genes work in concert to confer insecticide resistance. Analyses show for the first time that genes involved in neural cell function and survival are differentially regulated in an insecticide resistant insect. Furthermore, this team characterized a high degree of connectivity between genes and gene pathway that control cell stress response and survival. Mutations in genome regions of one gene were correlated with significant up-regulation in DDT resistant flies. These data are important to university, government and industry scientists interested in current difficulties found in controlling insect populations in the field, and will likely benefit producers by understanding how insects react to selection pressures and developing tactics to preserve the efficacy of current insect control technologies.

Technical Abstract: The adaptation of insect populations to insecticidal control is a continual threat human health and sustainable agriculture practices, but many complex genomic mechanisms involved remain poorly understood. A systems approach was applied to investigate the interconnections between structural and functional variance in response to Dichlorodiphenyltrichloroethane (DDT) within the Drosophila melanogaster strain 91-R. Directional selection in six selective sweeps were shown to have a cis-regulatory impact on constitutive gene expression in DDT resistant flies, which includes the most highly up-regulated transcript, unc-115b, which plays a central role in axon guidance. Analogously, the most highly down-regulated transcript the angiopoietin-like CG31832 is involved in directing vascular branching and dendrite outgrowth, but likely under trans-regulatory control. Direct functions and protein-protein interactions mediated by differentially-expressed transcripts control changes in cell migration, signal transduction, and gene regulatory cascades that impact the nervous system. Although changes to cellular stress response pathways involve eight different cytochrome P450s, stress response and apoptosis is controlled by a multi-facetted regulatory mechanism. These data demonstrate that DDT selection in 91-R resulted in genome-wide adaptation that impacts genetic and signal transduction pathways that converge to modify stress response, cell survival, and neurological functions. Furthermore, this study implicates the involvement of mulitgenic mechanisms in the adaptation to chemical insecticide which impact interconnected regulatory cascades. We propose the possibility that DDT selection within 91-R has acted systemically wherein pathway interactions may function to reinforce the epistatic effects of individual adaptive changes in an additive or non-additive basis.