The Olfactory Transcriptomes of Mice

Abstract

The olfactory (OR) and vomeronasal receptor (VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery.

Author Summary

The sense of smell in mice involves the detection of odors and pheromones by many hundreds of olfactory and vomeronasal receptors. The genes that encode these receptors account for around 5% of the whole gene catalog, but they are poorly understood because they are very similar to each other, and are thought to be turned on randomly in only a small number of cells. Here we use multiple gene expression technologies to curate and measure the activity of all the genes involved in the detection of odors and find evidence of many new ones. We show that most genes encoding olfactory and vomeronasal receptors have complex, multi-exonic structures that generate different isoforms. We find that some receptors are consistently more abundant in the nose than others, which suggests they are not turned on randomly. This may explain why mice are particularly sensitive to some odors, but less attuned to others. We find that overall males and females differ very little in gene expression, despite having altered behavioral responses to the same odors. Thus diversity in receptor expression can explain differences in odor sensitivity, but does not appear to dictate whether sex pheromones are differentially detected by males or females.