Genomic signatures of subterranean lifestyle and ecological adaptation in Myospalax

Background: Mammals exhibit diverse adaptations to varied habitats, yet the genomic mechanisms underlying these transitions remain incompletely understood. Here, we present a comparative genomic, epigenomic, and three-dimensional chromatin analysis of two closely related zokor species, Myospalax aspalax and Myospalax psilurus, which inhabit arid and humid subterranean environments, respectively. Results: We identified subterranean lineage-specific positively selected and rapidly evolving genes enriched for DNA repair, hypoxia response, blood vessel development, and fructose metabolism. M. psilurus showed a notable loss of olfactory receptor genes, expansion of pheromone-related gene families, and widespread activation of a specific ERVK transposable element family, accompanied by elevated DNA methylation, suggesting enhanced epigenetic defenses and ecological specialization. In contrast, M. aspalax showed selection in kidney and lipid metabolism genes. Large chromosomal inversions (> 1 Mb) overlapped islands of high genetic divergence (high-F_ST or high D_xy) and were enriched for sensory, reproductive, and DNA repair genes. Although chromatin compartments remained largely stable, large inversions disrupted topologically associating domains and preferentially occurred in regions characterized by longer chromatin loops. Inversion breakpoints were flanked by inverted repeats and segmental duplications—features characteristic of the formation mechanism of non-allelic homologous recombination, suggesting that both the spatial proximity and sequence architecture of these regions may predispose them to large inversions. Conclusions: Overall, our results illuminate the structural, regulatory, and evolutionary mechanisms underlying ecological divergence and highlight how genome architecture contributes to adaptive evolution in subterranean mammals.