RT Journal Article
SR Electronic
T1 Protein pheromone MUP20/Darcin is a vector and target of indirect genetic effects in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 265769
DO 10.1101/265769
A1 Sven O. Bachmann
A1 Ellen Cross
A1 Shireene Kalbassi
A1 Matthew Alexandar Sarraf
A1 Michael Anthony Woodley of Menie
A1 Stéphane J. Baudouin
YR 2018
UL http://biorxiv.org/content/early/2018/02/14/265769.abstract
AB Social behavior in animals is an adaptive process influenced by environmental factors and direct and indirect genetic effects. Indirect genetic effects (IGEs) include mechanisms by which individuals of particular genotypes can influence the behavioral phenotypes and genotypes (via modulated patterns of gene expression) of other individuals with different genotypes. In groups of adult mice, IGEs can be unidirectional, from one genotype to the other, or bidirectional, resulting in a homogenization of the behavioral phenotypes within the group. Critically, it has been theorized that IGEs constitute a large fitness target on which deleterious mutations can have pleiotropic effects, meaning that individuals carrying certain behavior-altering mutations can impose the fitness costs of those mutations on others comprising the broader social genome. Experimental data involving a mouse model support the existence of these IGE-amplified fitness losses; however, the underlying biological mechanisms that facilitate these remain unknown. In a mouse model of IGEs, we demonstrate that the Major Urinary Protein 20 pheromone, also called Darcin, produced by mice lacking the adhesion protein Neuroligin-3 acts as a vector to deleteriously modify the social behavior of wild-type mice. Additionally, we showed that lack of social interest on the part of Neuroligin-3 knockout mice is independent of their environment. These findings reveal a new role for mammalian pheromones in mediating the externalization of social deficits from one individual to others comprising the population through IGEs.Author Summary Indirect genetic effects (IGEs) are mechanisms by which individuals of particular genotypes can influence the behavioral phenotype of individuals of different genotypes, sometimes disruptively, in instances where one member of the population carriers a deleterious behavior altering variant. Although disruptive IGEs have been demonstrated in mice, its underlying molecular and genetic mechanisms remain unknown. Using an IGEs mouse model, we demonstrated that the pheromone protein Major Urinary Protein 20, also named Darcin, is as a vector and target of social epistasis a specific type of IGEs. This finding reveals a new function for mammalian pheromones in mediating social epistasis to degrade group social behavior.