Researchers from the Monell Center in Philadelphia and collaborating institutions have found that as much as 30% of the large array of human olfactory receptor differs between any two individuals.
This substantial variation is in turn reflected by variability in how each person perceives odors. We all have about 400 different types of specialized sensors, known as olfactory receptor proteins, that somehow work together to detect a large variety of odors.
"The activation pattern of these 400 receptors encodes both the intensity of an odor and the quality – for example, whether it smells like vanilla or smoke – for the tens of thousands of different odors that represent everything we smell," says study lead author Joel Mainland, PhD, a molecular biologist at Monell.
“Right now, nobody knows how the activity patterns are translated into a signal that our brain registers as the odor."
Added complexity
Mainland explains that understanding the complexity of odors is a challenging task and is made harder as the underlying amino acid sequence can vary slightly for each of the 400 receptor proteins, resulting in one or more variants for each of the receptors.
Each receptor variant responds to odors in a slightly different way and the variants are distributed across individuals such that nearly everyone has a unique combination of olfactory receptors.
To gain a better understanding of the extent of olfactory receptor variation and how this impacts human odor perception, Mainland and his collaborators used a combination of high-throughput assays to measure how single receptors and individual humans respond to odors.
The results, published in Nature Neuroscience, provide a critical step towards understanding how olfactory receptors encode the intensity, pleasantness and quality of odor molecules.
Testing
During the study, researchers first cloned 511 known variants of human olfactory receptors and embedded them in host cells that are easy to grow in the laboratory.
The next step was to measure whether each receptor variant responded to a panel of 73 different odor molecules. This process identified 28 receptor variants that responded to at least one of the odor molecules.
Drilling down, the researchers next examined the DNA of 16 olfactory receptor genes, discovering considerable variation within the genes for discrete receptors.
Mainland predicts that the olfactory receptors of any two individuals differ by about 30%, meaning that for any two randomly chosen individuals, approximately 140 of their 400 olfactory receptors will differ in how they respond to odor molecules.
"The long-term goal is to figure out how the receptors encode odor molecules well enough that we can actually create any odor we want by manipulating the receptors directly," adds Mainland. "In essence, this would allow us to 'digitize' olfaction."