Functional Evolution of Mammalian Odorant Receptors

Abstract

The mammalian odorant receptor (OR) repertoire is an attractive model to study evolution, because ORs have been subjected to rapid evolution between species, presumably caused by changes of the olfactory system to adapt to the environment. However, functional assessment of ORs in related species remains largely untested. Here we investigated 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. We functionally characterized the in vitro 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. 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.

Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals

“…Humans, chimpanzees, and macaques each have only one intact gene belonging to OGG2-2. The human gene (OR8K3) and its chimpanzee and macaque orthologs each reportedly bind (+)-menthol (Adipietro et al 2012). Mice have 17 OR genes belonging to OGG2-2, and all are located in one big cluster on chromosome 2.…”

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

“…Butyrate is one of the strongest smells to mammals and humans can detect it at concentrations of about 240 parts per billion (Fazzalari, 1978), possibly via the olfactory receptor OR51E1 (Adipietro et al, 2012). A plausible reason for the good butyrate odour sensitivity of the mammalian nose -usually perceived as a sickening, aversive smell at higher concentrations -is the fact that butyrate is a bacterial product that only occurs under anaerobic conditions, such as biological decomposition, putrefaction or fermentation, which potentially also produce harmful toxins.…”

Nasopalatine Ducts and Flehmen Behavior in the Mandrill: Reevaluating Olfactory Communication in Old World Primates

“…Other evidence, however, is incompatible with the purported trade-off between olfactory capabilities and trichromatic vision [Matsui et al, 2010], including with regard to the perception of sexual signals [Curtis et al, 1971;Leonhardt et al, 2009]. In sum, species may possess different functional vomeronasal genes [Giorgi & Rouquier, 2002] and Old World primates may not be as microsmatic as previously thought [Adipietro et al, 2012;Hübener & Laska, 1998;Laska et al, 2005].…”