Mammals employ large numbers of odorant receptors to sample and identify volatile chemicals in the environment. These receptors are thought to vary not only in specificity for particular odorants, but also in breadth of tuning. That is, some odorant receptors are narrowly focused on a few closely related structures, while other odorant receptors may be “broadly tuned”, responding to a wide variety of odorant structures. Here we have performed a detailed examination the mouse odorant receptor MOR256-17, demonstrating that this receptor is broadly tuned. This receptor responds to odorant structures that span a significant portion of a multi-dimensional odor space. However, we found that broad tuning was not a defining characteristic of other members the MOR256 subfamily. Two additional members of this odorant receptor subfamily (MOR256-8 and MOR256-22) were more narrowly focused on small sets of odorant structures. Interestingly, the receptive range of MOR256-17 encompassed a variety of nitrotoluenes, including various TNT synthesis intermediates, degradation products and TNT itself, suggesting the potential utility of odorant receptors in the development of sensing technologies for the detection of explosives and other forms of contraband.

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Mammals deploy a large array of odorant receptors (ORs) to detect and distinguish a vast number of odorant molecules. ORs vary widely in the type of odorant structures recognized and in the breadth of molecular receptive range (MRR), with some ORs recognizing a small group of closely related molecules and other ORs recognizing a wide range of structures. While closely related ORs have been shown to have similar MRRs, the functional relationships among less closely related ORs are unclear. We screened a small group of ORs with a diverse odorant panel to identify a new odorant-OR pairing (unsaturated aldehydes and MOR263-3). We then extensively screened MOR263-3 and a series of additional MORs related to MOR263-3 in various ways. MORs related by phylogenetic analysis (several other members of the MOR263 subfamily) had MRRs that overlapped with the MRR of MOR263-3, even with amino acid identity as low as 48% (MOR263-2). MOR171-17, predicted to be functionally related to MOR263-3 by an alternative bioinformatic analysis, but with only 39% amino acid identity, had a distinct odorant specificity. Our results support the use of phylogenetic analysis to predict functional relationships among ORs with relatively low amino acid identity.

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