Bank vole genomics links determinate and indeterminate growth of teeth.

Background: Continuously growing teeth are an important innovation in mammalian evolution, yet genetic regulation of continuous growth by stem cells remains incompletely understood. Dental stem cells responsible for tooth crown growth are lost at the onset of tooth root formation. Genetic signaling that initiates this loss is difficult to study with the ever-growing incisor and rooted molars of mice, the most common mammalian dental model species, because signals for root formation overlap with signals that pattern tooth size and shape (i.e., cusp patterns). Bank and prairie voles (Cricetidae, Rodentia, Glires) have evolved rooted and unrooted molars while retaining similar size and shape, providing alternative models for studying roots. Results: We assembled a de novo genome of Myodes glareolus, a vole with high-crowned, rooted molars, and performed genomic and transcriptomic analyses in a broad phylogenetic context of Glires (rodents and lagomorphs) to assess differential selection and evolution in tooth forming genes. Bulk transcriptomics comparisons of embryonic molar development between bank voles and mice demonstrated overall conservation of gene expression levels, with species-specific differences corresponding to the accelerated and more extensive patterning of the vole molar. We leverage convergent evolution of unrooted molars across the clade to examine changes that may underlie the evolution of unrooted molars. We identified 15 dental genes with changing synteny relationships and six dental genes undergoing positive selection across Glires, two of which were undergoing positive selection in species with unrooted molars, Dspp and Aqp1. Decreased expression of both genes in prairie voles with unrooted molars compared to bank voles supports the presence of positive selection and may underlie differences in root formation. Conclusions: Our results support ongoing evolution of dental genes across Glires and identify candidate genes for mechanistic studies of root formation. Comparative research using the bank vole as a model species can reveal the complex evolutionary background of convergent evolution for ever-growing molars. [ABSTRACT FROM AUTHOR]