Genetics of individual MUP variation

Sheehan MJ, Lee V, Corbett-Detig R, Bi K, Beynon RJ, Hurst JL, Nachman MW. (2016) Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice. PLoS Genet. 2016 Mar 3;12(3):e1005891. doi: 10.1371/journal.pgen.1005891.

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.