Centromeric tandem repeats expansions in plateau zokor enhance chromosome stability for high-altitude adaptation

Repetitive elements constitute nearly 50% of mammalian genomes; however, their roles in adaptive evolution remain poorly understood. Their identification and assembly, particularly for tandem repeats, are technically challenging, leading to their frequent omission from downstream analyses.

Here, we employ high-quality long-read sequencing to generate chromosome-level genome assemblies for four zokor species adapted to different altitudes. Comparative analyses reveal that the plateau zokor, the only species primarily inhabiting the high-altitude Qinghai-Tibet Plateau, exhibits an expanded genome size and a distinctive bimodal GC content distribution. These features are largely driven by the extensive expansion of a highly conserved tandem repeat, termed pzTR. Experimental analyses show that pzTR is widely distributed across plateau zokor chromosomes and is likely associated with centromeric regions. Functional assays further demonstrate that depletion of pzTR in plateau zokor cell lines disrupts genomic stability by impairing accurate chromosome segregation. Notably, chromosomes harboring pzTR display reduced mis-segregation rates, particularly under hypoxic conditions.

Together, these findings highlight the unique genomic architecture of the plateau zokor and suggest a critical role for centromeric tandem repeats in safeguarding genome stability under hypoxic stress associated with high-altitude environments.