Degl'Innocenti Andrea, Parrilla Marta, Harr Bettina, Teschke Meike
Max-Planck-Institut für Biophysik, Frankfurt am Main, Germany.
Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy.
PLoS One. 2016 Jan 21;11(1):e0144698. doi: 10.1371/journal.pone.0144698. eCollection 2016.
In 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.
Odorant 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.
Here 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.
In 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.
在脊椎动物中,鼻腔内的几个解剖区域介导嗅觉。其中,主要嗅觉上皮检测大多数传统气味剂。嗅觉感觉神经元具有暴露于空气中的纤毛,通过一个极其庞大的七跨膜化学感受器家族(称为气味受体)检测挥发性化学物质。它们的基因以单基因和单等位基因的方式表达:在给定的成熟神经元中,单个气味受体基因的单个等位基因通过一种仍未明确的分子机制(称为气味受体基因选择)进行转录。
气味受体基因通常排列在基因组簇中,但有少数基因在其转录本坐标上游和下游超过1 Mb的区域内与其他基因分离(我们称它们为孤立基因)。由于其调控元件的冗余性和模糊性,对簇状基因的研究存在问题:我们建议使用孤立基因作为简化模型来理解气味受体基因选择。
在这里,我们确定了小鼠基因组(C57BL/6J)中孤立基因的数量和身份,并评估了一些哺乳动物直系同源基因中孤立状态的保守性。此外,我们定位了它们的推定启动子,预测了它们的同源结构域结合位点(通常存在于气味受体基因的启动子中),并将候选启动子序列与野生捕获小鼠的序列进行比较。我们还提供了组织切片的表达数据。
在小鼠基因组中有八个完整的孤立基因:Olfr19(M12)、Olfr49、Olfr266、Olfr267、Olfr370、Olfr371、Olfr466、Olfr1402;其中五个在大鼠中作为孤立基因保守。这些基因都在三日龄小鼠的主要嗅觉上皮中表达。Olfr370的C57BL/6J候选启动子与其野生型对应物相比有很大差异。在Olfr266的推定启动子内预测到一个同源结构域结合位点。总体而言,我们的研究结果支持将Olfr266作为研究气味受体基因选择的模型基因。