Conserved and derived expression patterns and positive selection on dental genes reveal complex evolutionary context of ever-growing rodent molars

Background: Dental research has provided great insight into vertebrate evolution and ecology, yet the precise regulation of dental development and stem cells remains unknown. Dental stem cells in the apical pulp are lost during tooth root formation, but signaling at the onset of root formation overlaps with signals responsible for patterning tooth size and shape. Within the voles (Cricetidae, Rodentia, Glires), species have evolved both rooted and unrooted molars that have similar size and shape. 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. Results: Our de novo genome recovered 91% of single-copy orthologs for Euarchontoglires and had a total length of 2.44 Gigabases, enabling genomic and transcriptomic analyses. Genome-wide analyses across Glires identified 6 keystone dental genes undergoing positive selection and two genes undergoing positive selection in species with unrooted molars, Dspp and Aqp1. Transcriptomics analyses demonstrated conserved patterns of dental gene expression with species-specific variation likely related to developmental timing and morphological differences between mouse and vole molars. Conclusions: Our results provide evidence of ongoing dental genes evolution in rodents with unrooted molars. We identify candidate genes for further functional analyses, particularly Dspp, which plays an important role in mineralizing tissues. Our expression results support conservation of dental genes between voles and common model species like mice, while revealing the strong effect of overall tooth morphology on gene expression. ### Competing Interest Statement The authors have declared no competing interest.