Receptive range analysis of a mouse odorant receptor subfamily

Abstract

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.

An evolutionary conserved olfactory receptor for foodborne and semiochemical alkylpyrazines

“…This is corroborated by previous studies reporting that phylogenetically related mouse ORs had overlapping odorant specificities. 66,67 Another compound that was found in wolf urine and initially has been considered to be fear-inducing is 2,6-DMP. 9 In further tests by Osada et al (2011), this particular compound, however, failed to significantly induce fear reactions-its status as a semiochemical, thus, remains unclear.…”

Sequence-Based Prediction of Olfactory Receptor Responses

“…Sequence-based approaches to response prediction require a reasonably high homology among the receptors. In vertebrates, receptors with less than 40% sequence identity were found to have little overlap in their responses (Li et al 2015). The insects ORs presented a particularly difficult test case as they have only about 20 % homology among conspecific ORs; indeed, we found that there was no correlation between the overall sequence similarity and the response similarity among the ORs.…”

Presence of recombination hotspots throughout SLC6A3

“…Finally, this phylogenetic tree indicates a tendency of bidirectional diversion among the 114 18kb-haplotypes. By analyzing twenty six 1KGP populations together (thousands of haplotypes), a much stronger bidirectional diversion of the 18kb promoter was observed (without geographic correlation, data not shown), validating the COGA subjects-based finding and implying again a functional correlation between genetics of the SLC6A3 promoter and related phenotypes[103].…”