Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice

Abstract

Recognition of individuals by scent is widespread across animal taxa. Though animals can often discriminate chemical blends based on many compounds, recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice. The genetic nature of individuality in scent marks (e.g. coding versus regulatory variation) and the evolutionary processes that maintain diversity are poorly understood. The individual signatures in scent marks of house mice are the protein products of a group of highly similar paralogs in the major urinary protein ( Mup) gene family. Using the offspring of wild-caught mice, we examine individuality in the major urinary protein (MUP) scent marks at the DNA, RNA and protein levels. We show that individuality arises through a combination of variation at amino acid coding sites and differential transcription of central Mup genes across individuals, and we identify eSNPs in promoters. There is no evidence of post-transcriptional processes influencing phenotypic diversity as transcripts accurately predict the relative abundance of proteins in urine samples. The match between transcripts and urine samples taken six months earlier also emphasizes that the proportional relationships across central MUP isoforms in urine is stable. Balancing selection maintains coding variants at moderate frequencies, though pheromone diversity appears limited by interactions with vomeronasal receptors. We find that differential transcription of the central Mup paralogs within and between individuals significantly increases the individuality of pheromone blends. Balancing selection on gene regulation allows for increased individuality via combinatorial diversity in a limited number of pheromones.

Author Summary

Individual recognition via scent is critical for many aspects of behavior including parental care, competition, cooperation and mate choice. While animal scents can differ in a huge number of dimensions, recent work has shown that only some specialized semiochemicals in scent marks are behaviorally relevant for individual recognition. How is individuality in specialized semiochemical blends produced and maintained in populations? At the extremes, individuality may depend on either a plethora of semiochemical isoforms or on combinatorial variation in a small number of shared isoforms across individuals. Analyzing the major urinary protein (MUP) pheromone blends of a wild population of house mice, we find evidence in favor of a combinatorial diversity model for the production and maintenance of individuality. Balancing selection maintains MUP proteins at moderate frequencies in the population, though interactions with the pheromone receptors appear to limit the extent of pheromone diversity in the system. By contrast, differential transcription of proteins greatly increases individuality in pheromone blends with balancing selection maintaining diversity in promoter regions associated with gene expression patterns. Selection maintaining combinatorial diversity in a limited set of behaviorally important semiochemicals may be a widespread mechanism generating and maintaining individuality in scent across taxa.