Abstract
BackgroundIn vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice.AimOdorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice.ProceduresHere we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections.ResultsIn the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings favor Olfr266 as a model gene to investigate odorant receptor gene choice.
Highlights
In the mouse, the detection of chemicals for the sense of smell relies on four anatomically distinct regions: the main olfactory epithelium (MOE), the septal organ, the vomeronasal organ and the Grüneberg ganglion
MDAS: maximum distance as solitary, the genomic interval in which the odorant receptor gene is isolated, both upstream and downstream in respect to its transcript coordinates, from neighboring odorant receptor genes. a In absence of both an official name and an Ensembl gene identifier, we reported the identifier provided by Niimura et al [7]. b While reported for convenience, RanoOR12.2.1P is not strictly solitary according to our 1 Mb threshold criterion. c For Cavia porcellus, the average genomic scaffold length in the cavPor3 genome assembly is 8.9 Mb
It may not be possible to study unambiguously the regulatory sequences of a single OR gene that belongs to a cluster
Summary
The detection of chemicals for the sense of smell relies on four anatomically distinct regions: the main olfactory epithelium (MOE), the septal organ, the vomeronasal organ and the Grüneberg ganglion In these structures are located sensory neurons that express specific G-protein-coupled receptors, transmembrane proteins implicated in the signal transduction event that leads to the generation of smell perception [1][2][3][4][5][6]. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice
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