Insects use olfactory cues to locate hosts and mates. Pheromones and other semiochemicals are transported in the insect antenna by odorant-binding proteins (OBPs), which ferry the signals across the sensillum lymph to the olfactory receptors (ORs). In the silkworm, Bombyx mori (L.), two OBP subfamilies, the pheromone-binding proteins (PBPs) and the general odorant-binding proteins (GOBPs), are thought to be involved in both sensing and transporting the sex pheromone, bombykol [(10E,12Z)-hexadecadien-1-ol], and host volatiles, respectively. Quantitative examination of transcript levels showed that BmorPBP1 and BmorGOBP2 are expressed specifically at very high levels in the antennae, consistent with their involvement in olfaction. A partitioning binding assay, along with other established assays, showed that both BmorPBP1 and BmorGOBP2 bind to the main sex pheromone component, bombykol. BmorPBP1 also binds equally well to the other major pheromone component, bombykal [(10E,12Z)-hexadecadienal], whereas BmorGOBP2 discriminates between the two ligands. The pheromone analogs (10E,12Z)-hexadecadienyl acetate and (10E,12Z)-octadecadien-1-ol bind to both OBPs more strongly than does bombykol, suggesting that they could act as potential blockers of the response to sex pheromone by the male. These results are supported by further comparative studies of molecular docking, crystallographic structures, and EAG recording as a measure of biological response.
The genes that are required for organismal survival are annotated as ‘essential genes’. Identifying all the essential genes of an animal species can reveal critical functions that are needed during the development of the organism. To inform studies on mouse development, we developed a supervised machine learning classifier based on phenotype data from mouse knockout experiments. We used this classifier to predict the essentiality of mouse genes lacking experimental data. Validation of our predictions against a blind test set of recent mouse knockout experimental data indicated a high level of accuracy (>80%). We also validated our predictions for other mouse mutagenesis methodologies, demonstrating that the predictions are accurate for lethal phenotypes isolated in random chemical mutagenesis screens and embryonic stem cell screens. The biological functions that are enriched in essential and non-essential genes have been identified, showing that essential genes tend to encode intracellular proteins that interact with nucleic acids. The genome distribution of predicted essential and non-essential genes was analysed, demonstrating that the density of essential genes varies throughout the genome. A comparison with human essential and non-essential genes was performed, revealing conservation between human and mouse gene essentiality status. Our genome-wide predictions of mouse essential genes will be of value for the planning of mouse knockout experiments and phenotyping assays, for understanding the functional processes required during mouse development, and for the prioritisation of disease candidate genes identified in human genome and exome sequence datasets.
It is generally recognized that insect odorant binding proteins (OBPs) mediate the solubilisation and transport of hydrophobic odorant molecules and contribute to the sensitivity of the insect olfactory system. However, the exact mechanism by which OBPs deliver odorants to olfactory receptors and their role, if any, as selectivity filters for specific odorants, are still a matter of debate. In the case of Anopheles gambiae, recent studies indicate that ligand discrimination is effected through the formation of heterodimers such as AgamOBP1 and AgamOBP4 (odorant binding proteins 1 and 4 from Anopheles gambiae). Furthermore, AgamOBPs have been reported to be promiscuous in binding more than one ligand simultaneously and repellents such as DEET (N,N-diethyl-3-toluamide) and 6-MH (6-methyl-5-hepten-2-one) interact directly with mosquito OBPs and/or compete for the binding of attractive odorants thus disrupting OBP heterodimerisation. In this paper, we propose mechanisms of action of DEET and 6-MH. We also predict that ligand binding can occur in several locations of AgamOBP1 with partial occupancies and propose structural features appropriate for repellent pharmacophores.
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