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      Vapor detection and discrimination with a panel of odorant receptors

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          Abstract

          Olfactory systems have evolved the extraordinary capability to detect and discriminate volatile odorous molecules (odorants) in the environment. Fundamentally, this process relies on the interaction of odorants and their cognate olfactory receptors (ORs) encoded in the genome. Here, we conducted a cell-based screen using over 800 mouse ORs against seven odorants, resulting in the identification of a set of high-affinity and/or broadly-tuned ORs. We then test whether heterologously expressed ORs respond to odors presented in vapor phase by individually expressing 31 ORs to measure cAMP responses against vapor phase odor stimulation. Comparison of response profiles demonstrates this platform is capable of discriminating between structural analogs. Lastly, co-expression of carboxyl esterase Ces1d expressed in olfactory mucosa resulted in marked changes in activation of specific odorant-OR combinations. Altogether, these results establish a cell-based volatile odor detection and discrimination platform and form the basis for an OR-based volatile odor sensor.

          Abstract

          Biomimetic “noses” have been proposed to replace trained animals for chemical detection. Here the authors select 31 mouse olfactory receptors (ORs), based on a large cell-based screen of >800 ORs against seven chemicals, to build an OR-based sensor able to discriminate structurally similar compounds.

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          Most cited references55

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          Combinatorial receptor codes for odors.

          The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. Here we used a combination of calcium imaging and single-cell RT-PCR to identify odorant receptors (ORs) for odorants with related structures but varied odors. We found that one OR recognizes multiple odorants and that one odorant is recognized by multiple ORs, but that different odorants are recognized by different combinations of ORs. Thus, the olfactory system uses a combinatorial receptor coding scheme to encode odor identities. Our studies also indicate that slight alterations in an odorant, or a change in its concentration, can change its "code," potentially explaining how such changes can alter perceived odor quality.
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            Odor coding by a Mammalian receptor repertoire.

            Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of more than 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and for unraveling mammalian odor coding.
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              Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals

              Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species—reflecting the respective species' lifestyles—and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory.
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                Author and article information

                Contributors
                hiroaki.matsuami@duke.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                1 November 2018
                1 November 2018
                2018
                : 9
                : 4556
                Affiliations
                [1 ]ISNI 0000000100241216, GRID grid.189509.c, Department of Molecular Genetics and Microbiology, , Duke University Medical Center, ; Durham, NC 27710 USA
                [2 ]GRID grid.136594.c, Department of Mechanical Systems Engineering, , Tokyo University of Agriculture and Technology, ; Koganei, Tokyo 184-8588 Japan
                [3 ]GRID grid.136594.c, Department of Biotechnology and Life Science, , Tokyo University of Agriculture and Technology, ; Koganei, Tokyo 184-8588 Japan
                [4 ]ISNI 0000 0000 9142 2735, GRID grid.250221.6, Monell Chemical Senses Center, ; Philadelphia, PA 19104 USA
                [5 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Department of Neuroscience, University of Pennsylvania, ; Philadelphia, PA 19104 USA
                [6 ]ISNI 0000000100241216, GRID grid.189509.c, Department of Neurobiology, Neurobiology graduate program, , Duke University Medical Center, ; Durham, NC 27710 USA
                [7 ]GRID grid.136594.c, Institute of Global Innovation Research, , Tokyo University of Agriculture and Technology, ; Koganei, Tokyo 184-8588 Japan
                [8 ]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Duke Institute for Brain Sciences, , Duke University, ; Durham, NC 27710 USA
                [9 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Present Address: Department of Radiation Oncology, Helen Diller Comprehensive Cancer Center, , University of California San Francisco, ; San Francisco, CA USA
                Author information
                http://orcid.org/0000-0002-3716-8590
                http://orcid.org/0000-0002-5056-4598
                http://orcid.org/0000-0002-1928-1338
                http://orcid.org/0000-0001-8307-9671
                http://orcid.org/0000-0002-8850-2608
                Article
                6806
                10.1038/s41467-018-06806-w
                6212438
                30385742
                903b78b1-e53f-4cb8-9076-c74770b8e2d9
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 February 2018
                : 4 September 2018
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