Differential methylation, epigenetic clocks, and island-mainland divergence in an insectivorous small mammal

Geographically isolated populations, including island-mainland populations, tend to exhibit phenotypic variation in many species. The so-called island syndrome occurs when different environmental pressures lead to insular divergence from mainland populations. This phenomenon can be seen in an island population of Nova Scotia masked shrews ( Sorex cinereus ), which have developed a specialized feeding habit and digestive enzyme compared to their mainland counterparts. Epigenetic modifications, such as DNA methylation (DNAm), can impact phenotypes by altering gene expression without changing the DNA sequence. Here, we used a de novo masked shrew genome assembly and epigenome-wide assay to investigate morphological and DNA methylation patterns between island and mainland populations. Island shrews were morphologically and epigenetically different than their mainland counterparts, exhibiting a smaller body size; remarkably, the gene ontology analyses mirrored these phenotypes including genes for the digestive enzyme phenotypes. Moreover, island shrews appeared to age faster than their mainland counterparts. This study provides an example counter to the prevailing island syndrome morphological patterns, along with novel epigenomic insight into the drivers of island-mainland divergence in mammals. ### Competing Interest Statement SH is a founder of the non-profit Epigenetic Clock Development Foundation, which plans to license several of his patents from his employer UC Regents. The other authors declare no conflicts of interest.