Morphological and genomic shifts in mole- rat ‘queens’ increase fecundity but reduce skeletal integrity

In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding ‘queen’ status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also upregulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.Supplementary file 1. Table summarizing study animals.Supplementary file 2. Table of results of mixed effects model of mole-rat gene expression data testing for effect of solitaire versus helper social status. bone_0 refers to long bones; bone_1 refers to lumbar vertebrae.Supplementary file 3. Table of results of multivariate model explaining litter size (first model) or pup mass (second model).Supplementary file 4. Table of results of mixed effects model of mole-rat gene expression data. bone0 refers to long bones; bone1 refers to lumbar vertebrae.Supplementary file 5. Table of proportions of cell types estimated with CIBERSORT, based on reference gene expression levels for 412 marker genes in 27 purified mouse cell types (Hume et al., 2010).Supplementary file 6. Table of 95% confidence intervals of mediation analysis testing for cell-type proportions as mediating the effect of queen status on gene expression (in long bones or in lumbar vertebrae).Supplementary file 7. Table of Gene Ontology (GO) enrichment results of genes upregulated with queen status.Supplementary file 8. Table of transcription factor binding motifs enriched in open chromatin regions near genes upregulated with queen status.Supplementary file 9. Table of sample info for bone sections stained with Safranin O.Supplementary file 10. Table of effects of number of total offspring on mean cortical thickness per femur shaft decile.Supplementary file 11. Transparent reporting form.The Human Frontier Science Program, the National Science Foundation, the National Institutes of Health, a Sloan Foundation Early Career Research Fellowship, a Foerster-Bernstein Postdoctoral Fellowship and a Natural Environmental Research Council Doctoral Training Program. This research is part of a project that has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme. High-performance computing resources were supported by the North Carolina Bio- technology Center.http://elifesciences.orgam2022Mammal Research InstituteZoology and Entomolog