If an olfactory receptor is expressed in your kidneys, what do they smell?

1 minute read

A reminder of the complexity of gene networks and their regulation:

Functional expression of the olfactory signaling system in the kidney
Jennifer L. Pluznick et al.
Olfactory-like chemosensory signaling occurs outside of the olfactory epithelium. We find that major components of olfaction, including olfactory receptors (ORs), olfactory-related adenylate cyclase (AC3) and the olfactory G protein (Golf), are expressed in the kidney. AC3 and Golf colocalize in renal tubules and in macula densa (MD) cells which modulate glomerular filtration rate (GFR). GFR is significantly reduced in AC3?/? mice, suggesting that AC3 participates in GFR regulation. Although tubuloglomerular feedback is normal in these animals, they exhibit significantly reduced plasma renin levels despite up-regulation of COX-2 expression and nNOS activity in the MD. Furthermore, at least one member of the renal repertoire of ORs is expressed in a MD cell line. Thus, key components of olfaction are expressed in the renal distal nephron and may play a sensory role in the MD to modulate both renin secretion and GFR.

On one level it makes perfect sense: you’ve got a highly specific molecule-sensing apparatus in one part of the body, and another part needs to detect some molecules and send signals about them. Evolution might well reuse parts of one system in the service of the other.

On another level, it shows the difficulty of testing hypotheses about the evolution of single genes. The olfactory receptor genes have been repeated targets of selection in human (and primate) evolution. There has been a differential loss of functional OR genes in some primate lineages, including ours. A natural hypothesis is that we don’t need to smell things that other mammals still need to smell, because primates are more vision-centric in their foraging and mating behavior.

But then, what about the kidneys? Or other possible functions of OR genes in the body? Do they dampen the signal of selection? Enhance it? Are they independent of it? Are their kidney-specific regulatory elements for these genes? Or are there functional variants in olfaction that have functional side effects elsewhere?

And what does any of this have to do with asparagus pee?

Complicated.