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The microbial ars operon encodes the primary bacterial defense response to the environmental toxicant, arsenic. An important component of this operon is the arsR gene, which encodes ArsR, a member of the family of proteins categorized as DNA-binding transcriptional repressors. As currently documented, ArsR regulates its own expression as well as other genes in the same ars operon. This study examined the roles of four ArsR proteins in the well-developed model Gram-negative bacterium Agrobacterium tumefaciens 5A. RNASeq was used to compare and characterize gene expression profiles in ± arsenite-treated cells of the wild-type strain and in four different arsR mutants. We report that ArsR-controlled transcription regulation is truly global, extending well beyond the current ars operon model, and includes both repression as well as apparent activation effects. Many cellular functions are significantly influenced, including arsenic resistance, phosphate acquisition/metabolism, sugar transport, chemotaxis, copper tolerance, iron homeostasis, and many others. While there is evidence of some regulatory overlap, each ArsR exhibits its own regulatory profile. Furthermore, evidence of a regulatory hierarchy was observed; i.e. ArsR1 represses arsR4 , ArsR4 activates arsR2 , and ArsR2 represses arsR3 . Additionally and unexpectedly, aioB (arsenite oxidase small subunit) expression was shown to be under partial positive control by ArsR2 and ArsR4. Summarizing, this study demonstrates the regulatory portfolio of arsenite-activated ArsR proteins and includes essentially all major cellular functions. The broad bandwidth of arsenic effects on microbial metabolism assists in explaining and understanding the full impact of arsenic in natural ecosystems, including the mammalian gut. 

Plant–insect interactions are ubiquitous, and have been studied intensely because of their relevance to damage and pollination in agricultural plants, and to the ecology and evolution of biodiversity. Variation within species can affect the outcome of these interactions. Specific genes and chemicals that mediate these interactions have been identified, but genome‐ or metabolome‐scale studies might be necessary to better understand the ecological and evolutionary consequences of intraspecific variation for plant–insect interactions. Here, we present such a study. Specifically, we assess the consequences of genome‐wide genetic variation in the model plantMedicago truncatulaforLycaeides melissacaterpillar growth and survival (larval performance). Using a rearing experiment and a whole‐genome SNP data set (>5 million SNPs), we found that polygenic variation inM. truncatulaexplains 9%–41% of the observed variation in caterpillar growth and survival. Genetic correlations among caterpillar performance and other plant traits, including structural defences and some anonymous chemical features, suggest that multipleM. truncatulaalleles have pleiotropic effects on plant traits and caterpillar performance (or that substantial linkage disequilibrium exists among distinct loci affecting subsets of these traits). A moderate proportion of the genetic effect ofM. truncatulaalleles onL. melissaperformance can be explained by the effect of these alleles on the plant traits we measured, especially leaf toughness. Taken together, our results show that intraspecific genetic variation inM. truncatulahas a substantial effect on the successful development ofL. melissacaterpillars (i.e., on a plant–insect interaction), and further point toward traits potentially mediating this genetic effect.