Principle of Cooperativity in Olfactory Receptor Selection

Abstract

In this case study we will discuss how mathematical modeling provides mechanistic insight on an intriguing problem of olfactory receptor selection. Olfaction, or the sense of smell, is essential for the survival of most living organisms. Therefore, many organisms have developed sophisticated olfactory sensing systems. For example, millions of olfactory sensory neurons (OSNs) reside at the back the nasal epithelium of a human nose. Each neuron has many copies of transmembrane G-protein coupled olfactory receptors (ORs). Odorants bind to the receptors, trigger some conformational change, and the neurons send electric signals to the brain so we can smell different odors. Given that genes encoding ORs form the largest superfamily of vertebrate genomes, an amazing observation is that each neuron only expresses one type of the receptors, actually one allele of the OR gene [1]. Richard Axel and Linda Buck received the 2004 Nobel Prize in Physiology or Medicine for discovering the receptors and this monoallelic expression phenomenon. But the mechanism for monoallelic OR expression remains unknown for decades. We will see that this seemingly “mission impossible” can be achieved from some very simple physics principles that we are familiar with from everyday life.