In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities emerge from the deleterious interactions between alleles that are neutral or advantageous in the original genetic backgrounds, i.e., negative epistatic effects. Within species such interactions are responsible for outbreeding depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities in the nematode Caenorhabditis elegans by looking for genomic regions that disrupt egg laying; a complex, highly regulated, and coordinated phenotype. Investigation of introgression lines and recombinant inbred lines derived from the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results are inconsistent with a model of pairwise interaction between two loci, suggesting that the incompatibilities are a consequence of complex interactions between multiple loci. Analysis of additional life history traits indicates that the QTL regions identified in these screens are associated with effects on other traits such as lifespan and reproduction, suggesting that the incompatibilities are likely to be deleterious. Taken together, these results indicate that numerous BDM incompatibilities that could contribute to reproductive isolation can be detected and mapped within C. elegans.

The goal of the present study was to obtain an in vivo relevant prioritization method for the endocrine potencies of different polycarbonate monomers, by combining in vitro bioassay data with physiologically based kinetic (PBK) modelling. PBK models were developed for a selection of monomers, including bisphenol A (BPA), two bisphenol F (BPF) isomers and four different bisphenol A diglycidyl ethers (BADGEs), using in vitro input data. With these models, the plasma concentrations of the compounds were simulated, providing means to estimate the dose levels at which the in vitro endocrine effect concentrations are reached. The results revealed that, whereas the in vitro relative potencies of different BADGEs (predominantly anti-androgenic effects) can be up to fourfold higher than BPA, the estimated in vivo potencies based on the oral equivalent doses are one to two orders of magnitude lower than BPA because of fast detoxification of the BADGEs. In contrast, the relative potencies of 2,2-BPF and 4,4-BPF increase when accounting for the in vivo availability. 4,4-BPF is estimated to be fivefold more potent than BPA in humans in vivo in inducing estrogenic effects and both 2,2-BPF and 4,4-BPF are estimated to be, respectively, 7 and 11-fold more potent in inducing anti-androgenic effects. These relative potencies were considered to be first-tier estimates, particularly given that the potential influence of intestinal metabolism on the in vivo availability was not accounted for. Overall, it can be concluded that both 2,2-BPF and 4,4-BPF are priority compounds.