Smell is an essential sense that allows animals to find food and mates while avoiding predators. In humans smell is considered an aesthetic sensory modality, but olfactory disorders may presage neurological disease including Parkinson's, Alzheimer's, and schizophrenia. The odorant receptors (ORs) comprise the largest gene family in mammals and endow an animal with the ability to smell. Critical to the development and function of olfaction is the regulation of OR gene transcription, with each sensory neuron selecting just one OR for expression, at random, from only one allele. While recent experiments have brought the outlines of this remarkable process into focus,the core mechanism has remained obscure. Using a genetic approach in mice we present data that supports a model of single OR gene choice initiated by infrequent, stochastic transcriptional activation and governed by feedback suppression mechanism.

In the face extreme requirements for diversity, cells and organisms have evolved stochastic processes of gene regulation. Such mechanisms may allow for the maximal exploration of critical biochemical, genetic, or cellular spaces and maximize the informational output of the genome. The pursuit of the solution to this question of gene regulation has captivated the biomedical research community - not only in the area of neurobiology. The elucidation of this problem will shed light on the establishment and function of this sensory system and also further our understanding of the regulation of the largest gene family in mammals. Additionally, these findings will have central relevance for other examples of stochastic gene regulation such as the expression of the lymphocyte antigen receptors, X chromosome inactivation, for diverse disease-related processes such as trypanosome and malaria gene switching, and the functional (epigenetic) loss of heterozygosity in cancer; all of which likely depend on complex transcriptional processes.


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  1. B. Shykind, Regulation of mammalian odorant receptor genes, QFARF Proceedings, 2010, BMP19.
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