FoundationalConceptsNeuroscience

with about 350 different olfactory receptor proteins. Each different
GPCR responds to molecules having specific molecular shapes, just as
different GPCR neurotransmitter receptors are activated by different
neurotransmitter and drug (agonist) molecules.
In addition to its 350 genes coding for 350 functioning olfactory
GPCRs, the human genome has a large number of nonfunctional genes
that, although they appear to code for olfactory GPCRs, are altered in
some way so that they do not code for functional receptor proteins—
these are called pseudogenes. Humans have about six hundred olfac-
tory pseudogenes. It is speculated that, in our evolutionary past, our
distant ancestors possessed many more functional olfactory receptor
types (similar to the mouse of today) and a correspondingly more
sophisticated sense of smell. It is believed that, as our evolutionary
ancestors migrated from living close to the ground (where odorants
are a crucial source of environmental information) to living in trees
and, eventually, to being upright creatures with noses along way
from the ground (and vision becoming more important for collecting
environmental information), functional olfactory receptors were
lost through mutation, even though remnants of the ancient genes
remain.
It is likely we are still missing an interesting part of the story here.
Why would such a large number of nonfunctional genes be main-
tained over millions of years of evolutionary history? They may serve
some sort of important regulatory function—something is likely
going on here, and we don’t yet know what it is.
Our 350 different functional olfactory GPCRs give us the ability to
detect and discriminate thousands (at least!) of different odors—here’s
how. A particular odorant molecule will differentially activate to
varying extents some subset of olfactory GPCRs. Thus, odorant X may
bind, say, to olfactory receptor proteins 23, 77, 136, 242, 290, 312,