Dec 172019
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Due to technical improvements during the last years, machines outcompete humans in a couple of specialized tasks: Whereas it can take a human person very long to calculate the square root of a (non-square) number, a computer can finish this calculation at high precision within a fraction of a second. However, there are some areas in which machines still cannot compete with nature (yet). One of them is olfaction: Currently, no device is available that could replace police dogs with the ability to detect trace amounts of molecules. Similarly, farmers sometimes even train pigs to search for truffles hidden in the soil. Of course, the ability to detect relevant molecules in low amounts offers an enormous advantage and is thus subject to extensive optimization by evolution.
L’odorat, Honoré Daumier (circa 1839, public domain – wikimedia)

How exactly olfaction works in higher organisms has not been known for a long time. Nonetheless, it had been intuitively clear that there must be specific receptors interacting with the corresponding odours. This simple assumption has a remarkable consequence: Since mammals can distinguish a high number of odours, there also must be a high number of different receptors encoded in the genome. Indeed, the two scientists Linda Buck and Richard Axel discovered a comparatively large family of genes encoding for odorant receptors [1]. For this discovery, they were awarded the Nobel Prize in Physiology or Medicine in 2004. The activation of these receptors on the cell surface always results in similar intracellular reactions. If a cell had receptors for different odour molecules on its surface, it could therefore not distinguish these odours. In accordance to this consideration, it turned out that each olfactory cell only carries one type of all the different odorant receptors encoded in its genome. Why exactly this is the case is still not known in detail to date. Even more surprisingly, it even turned out that the axons of cells, which carry the same type of odorant receptor on their surface, end on the same set of cells.

An odour can of course consist of several kinds of molecules. The activation of different combinations of olfactory sensory neurons further increases the number of differentiable odours. A phenomenon seemingly similar to the exclusive expression of a single odorant receptor by an olfactory sensory neuron is the generation of only one type of antigen receptor by immune cells. They achieve this by a complicated recombination of genes, which is clearly not observed in olfactory neurons.

Investigating how a biological structure develops is often very helpful: In a later work, Linda Buck could show that in contrast to mature olfactory neurons, there are multiple mRNAs for different odorant receptors in immature neurons [2]. Why cells of our body can have entirely different morphologies and properties even though they all carry a copy of the same genome is a fundamental question which keeps many biologists busy. It is the differential expression of the genes in a cell, which causes these differences. This gives muscle cells the ability to contract and enables neurons to generate action potentials.

However, all olfactory neurons express a very similar pattern of genes except for their odorant receptor. One of the reasons for the transcription of different amounts of RNAs from different genes is the spatial arrangement of the DNA in the nucleus. Had it not been tightly packed into the nucleus, the DNA in each cell would have a total length of 1.8 m and highly condensed sections of DNA are usually not accessible for transcription into RNA. Stavros Lomvardas, a former member of the group of Richard Axel, could show that DNA segments encoding for odorant receptors on different chromosomes get pulled close to each other in a small spatial region in the nucleus. Interactions between the different DNA segments encoding for odorant receptors could contribute to the exclusive transcription of one specific odorant receptor gene [3,4].

The relevance of the spatial arrangement of the DNA within the nucleus for gene expression is an open question of major interest beyond olfaction. To which degree there is a specific nuclear arrangement of DNA and how this is established after cell division would then be further important for other unsolved questions in biology.

— Tobias Ruff


  • [1] Buck, L. and Axel, R. , A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 1991, 65-1 PP175-187 DOI:10.1016/0092-8674(91)90418-x
  • [2] Hanchate, N. K. and Kondoh, K. and Lu, Z. and Kuang, D. and Ye, X. and Qiu, X. and Pachter, L. and Trapnell, C. and Buck, L. B. , Science 2015, 350-6265 PP1251–1255
  • [3] Clowney, E. J. and LeGros, M. A. and Mosley, C. P. and Clowney, F. G. and Markenskoff-Papadimitriou, E. C. and Myllys, M. and Barnea, G. and Larabell, C. A. and Lomvardas, S., Cell 2012, 151-4 PP724–737
  • [4] Markenscoff-Papadimitriou, E. and Allen, W. E. and Colquitt, B. M. and Goh, T. and Murphy, K. K. and Monahan, K. and Mosley, C. P. and Ahituv, N. and Lomvardas, S., Cell 2014, 159-3 PP543–557