Data for Percival etal. 2017

Data for Percival etal. 2017



Previous analysis suggested that the relative contribution of individual bones to regional skull lengths differ between inbred mouse strains. If the negative correlation of adjacent bone lengths is associated with genetic variation in a heterogeneous population, it would be an example of negative pleiotropy, which occurs when a genetic factor leads to opposite effects in two phenotypes. Specifically, this negative pleiotropy might represent a mechanism of developmental constraint that limits variation in overall skull morphology while allowing for variation in the length of contributing bones. Confirming the negative pleiotropy of adjacent bones and determining the basis of this phenomenon may reveal important information about the maintenance of overall skull integration and skull element loss.


We identified negative correlations between the lengths of the frontal and parietal bones in the midline cranial vault as well as the jugal bone and jugal process of the maxilla, which contribute to the zygomatic arch. Through gene association mapping of a large heterozygous population of Diversity Outbred (DO) mice, we identified a candidate region on chromosome 17 driving the antagonistic contribution of the two zygomatic arch bones to total zygomatic arch length, an example of negative pleiotropy. Candidate genes in this region were identified and real-time PCR of the maxillary processes of DO founder strain embryos indicated differences in the RNA expression levels for two of the candidate genes.


A genomic region underlying negative pleiotropy of two zygomatic arch bones was identified. This negative pleiotropy provides a mechanism for antagonism in component bone lengths while constraining overall zygomatic arch length. This may contribute to variation in the contribution of individual bones to the zygomatic arch noted across mammals, including the derived increase in maxillary contribution to the rodent zygomatic arch and the severe reduction of the jugal bone in many mole species. Given that similar genetic and developmental mechanisms may underlie negative correlations in other parts of the skull, these results provide an important step towards understanding the developmental basis of evolutionary variation and constraint in skull morphology.