The Functional Evolution of Mammalian Odorant Receptors

Abstract

<p>The ability to detect small volatile molecules in the environment is mediated by the large repertoire of odorant receptors (ORs) in each species. The mammalian OR repertoire is an attractive model to study evolution because ORs have been subjected to rapid gene gains and losses between species, presumably caused by changes of the olfactory system to adapt to the environment. Despite the complicated history, clear orthologs--genes related via speciation--can still be identified even in distantly related species. Functional assessment of ORs in related species remains largely untested and sequence similarity is often used as a proxy for functional data. </p><p>Here I describe the functional properties of primate and rodent ORs to determine how well evolutionary distance predicts functional characteristics. Using human and mouse ORs with previously identified ligands, we cloned 18 OR orthologs from chimpanzee and rhesus macaque and 17 mouse-rat orthologous pairs that are broadly representative of the OR repertoire. Using a heterologous expression system, we functionally characterized the responses of ORs to a wide panel of odors and found similar ligand selectivity but dramatic differences in response magnitude. 87% of human-primate orthologs and 94% of mouse-rat orthologs showed differences in receptor potency (EC50) and/or efficacy (dynamic range) to an individual ligand. Notably dN/dS ratio, an indication of selective pressure during evolution, does not predict functional similarities between orthologs. Additionally, we found that orthologs responded to a common ligand 82% of the time, while human OR paralogs of the same subfamily responded to the common ligand only 33% of the time. </p><p>Our results suggest that while OR orthologs tend to show conserved ligand selectivity, their potency and/or efficacy dynamically change during evolution, even in closely related species. These functional changes in orthologs provide a platform for examining how the evolution of ORs can meet species-specific demands.</p>