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Background The evolution of embryological development has long been characterized by deep conservation. In animal development, the phylotypic stage in mid-embryogenesis is more conserved than either early or late stages among species within the same phylum. Hypotheses to explain this hourglass pattern have focused on purifying the selection of gene regulation. Here, we propose an alternative—genes are regulated in different ways at different stages and have different intrinsic capacities to respond to perturbations on gene expression. Results To eliminate the influence of natural selection, we quantified the expression variability of isogenetic single embryo transcriptomes throughout fly Drosophila melanogaster embryogenesis. We found that the expression variability is lower at the phylotypic stage, supporting that the underlying regulatory architecture in this stage is more robust to stochastic variation on gene expression. We present evidence that the phylotypic stage is also robust to genetic variations on gene expression. Moreover, chromatin regulation appears to play a key role in the variation and evolution of gene expression. Conclusions We suggest that a phylum-level pattern of embryonic conservation can be explained by the intrinsic difference of gene regulatory mechanisms in different stages.

SummaryEukaryotic genomes encode several well-studied buffering mechanisms that robustly maintain invariant phenotypic outcome despite fluctuating environmental conditions. Here we show that the gut microbiota, represented by a single Drosophila facultative symbiont, Lactobacillus plantarum (LpWJL), acts also as a broad genetic buffer that masks the contribution of the cryptic genetic variations in the host under nutritional stress. During chronic under-nutrition, LpWJL consistently reduces variation in different host phenotypic traits and ensures robust organ patterning; LpWJL also decreases genotype-dependent expression variation, particularly for development-associated genes. We further demonstrate that LpWJL buffers via reactive oxygen species (ROS) signaling whose inhibition severely impairs microbiota-mediated phenotypic robustness. We thus identified an unexpected contribution of facultative symbionts to Drosophila fitness by assuring developmental robustness and phenotypic homogeneity in times of nutritional stress.

SummaryIn recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here that these antibiotics induce a mitonuclear protein imbalance through their effects on mitochondrial translation, an effect that likely reflects the evolutionary relationship between mitochondria and proteobacteria. Even at low concentrations, tetracyclines induce mitochondrial proteotoxic stress, leading to changes in nuclear gene expression and altered mitochondrial dynamics and function in commonly used cell types, as well as worms, flies, mice, and plants. Given that tetracyclines are so widely applied in research, scientists should be aware of their potentially confounding effects on experimental results. Furthermore, these results caution against extensive use of tetracyclines in livestock due to potential downstream impacts on the environment and human health.