Synchronous evolution of an odor biosynthesis pathway and behavioral response

Area of Science:

• Olfactory communication
• Evolutionary biology
• Animal behavior

Background:

• Rodents rely on olfactory cues for species-specific behaviors, such as mate attraction.
• The specific odors and receptors involved in this rapid olfactory signaling evolution remain largely unknown.

Purpose of the Study:

• To identify the chemosignal and olfactory receptor responsible for species-specific social communication in mice.
• To investigate the evolutionary origins and mechanisms of this olfactory signaling pathway.

Main Methods:

• Identification of trimethylamine as a key mouse chemosignal.
• Characterization of trace amine-associated receptor 5 (TAAR5) as its olfactory receptor.
• Analysis of trimethylamine biosynthesis pathway, including FMO3 enzyme activity and Fmo3 gene regulation.
• Behavioral assays using wild-type, TAAR5 knockout mice, and trimethylamine-depleted conditions.

Main Results:

• Trimethylamine production increased significantly in the Mus lineage, involving commensal microflora and sex-dependent FMO3 activity.
• Male-specific Fmo3 gene repression was a recent evolutionary acquisition in Mus.
• Trimethylamine attracts mice and repels rats, with TAAR5 being essential for this attraction.
• Enzymatic depletion of trimethylamine or TAAR5 knockout impaired mouse scent attraction.

Conclusions:

• Trace amine-associated receptor 5 (TAAR5) is an evolutionarily conserved receptor critical for species-specific mouse behavior.
• Synchronized evolution of odor biosynthesis and odor-evoked behaviors ensures appropriate social interactions.