The human olfactory transcriptome

Abstract

BackgroundOlfaction is a versatile sensory mechanism for detecting thousands of volatile odorants. Although molecular basis of odorant signaling is relatively well understood considerable gaps remain in the complete charting of all relevant gene products. To address this challenge, we applied RNAseq to four well-characterized human olfactory epithelial samples and compared the results to novel and published mouse olfactory epithelium as well as 16 human control tissues.ResultsWe identified 194 non-olfactory receptor (OR) genes that are overexpressed in human olfactory tissues vs. controls. The highest overexpression is seen for lipocalins and bactericidal/permeability-increasing (BPI)-fold proteins, which in other species include secreted odorant carriers. Mouse-human discordance in orthologous lipocalin expression suggests different mammalian evolutionary paths in this family.Of the overexpressed genes 36 have documented olfactory function while for 158 there is little or no previous such functional evidence. The latter group includes GPCRs, neuropeptides, solute carriers, transcription factors and biotransformation enzymes. Many of them may be indirectly implicated in sensory function, and ~70 % are over expressed also in mouse olfactory epithelium, corroborating their olfactory role.Nearly 90 % of the intact OR repertoire, and ~60 % of the OR pseudogenes are expressed in the olfactory epithelium, with the latter showing a 3-fold lower expression. ORs transcription levels show a 1000-fold inter-paralog variation, as well as significant inter-individual differences. We assembled 160 transcripts representing 100 intact OR genes. These include 1–4 short 5’ non-coding exons with considerable alternative splicing and long last exons that contain the coding region and 3’ untranslated region of highly variable length. Notably, we identified 10 ORs with an intact open reading frame but with seemingly non-functional transcripts, suggesting a yet unreported OR pseudogenization mechanism. Analysis of the OR upstream regions indicated an enrichment of the homeobox family transcription factor binding sites and a consensus localization of a specific transcription factor binding site subfamily (Olf/EBF).ConclusionsWe provide an overview of expression levels of ORs and auxiliary genes in human olfactory epithelium. This forms a transcriptomic view of the entire OR repertoire, and reveals a large number of over-expressed uncharacterized human non-receptor genes, providing a platform for future discovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2960-3) contains supplementary material, which is available to authorized users.

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

“…Based on this observation, we assume that the OR expression in the human retina is sufficiently high to be an indicator of functionality. The fact that ORs are also weakly to moderate expressed in term of FPKM value in the olfactory epithelium, where they perform their main task in mediating olfaction, and in other cell types such as keratinocytes, where they are involved in growth processes, support this assumption (Olender et al, 2016; Tsai et al, 2016). …”

“…The expression profile of ORs in retina and TG/DRG are very similar. Several putative OR transcripts were also detectable in brain and testis, whereby recently published RNAseq data revealed that only five ORs (OR2A4/7, OR2L2, OR2M4 OR2W3 and OR5P3; mFPKM value ≥0.3) were detectable in human olfactory epithelium (Olender et al, 2016). This finding implies that the function of ORs expressed in the retina but not found in olfactory epithelium cannot be directly connected to the sense of smell.…”

“…According to our current findings, we can extend the OR6B3 expression profile to another sensory system, the retina. The assumption that this particular receptor has a vital function apart from olfaction is supported by the finding that its expression in the human olfactory epithelium is not clear (mFPKM 0.05; TPM 0.13; Olender et al, 2016). …”

“…The FPKM values of four TG datasets were combined and presented as the mFPKM. The human olfactory epithelium raw data were taken from (Olender et al, 2016). The data were bound and presented with the mean transcripts per million (TPM) of the four samples.…”

Poor human olfaction is a 19th-century myth

“…However, follow up work from a broader range of species found no support for a sudden loss of functional odor receptor genes in conjunction with trichromacy (21). Critically, new evidence shows that 60% of human olfactory receptor “pseudogenes” are actually transcribed into mRNA in the human olfactory epithelium (22) and work in model organisms suggests that some olfactory receptor pseudogenes may actually result in functional receptors (23). Should these non-coding RNAs or unexpectedly-coding RNAs turn out to be a powerful regulatory network unique to primates (say, for matching olfactory receptor gene expression to the environment; 24, 25), would we then conclude that it is the basis for superior olfactory function in primates?…”