The Vulpes vulpes montana genome provides insights into high-altitude adaptation mechanisms of the Vulpes species.

Vulpes vulpes montana (V. v. montana) and Vulpes ferrilata (V. ferrilata) are the only two Vulpes species known to inhabit the Qinghai-Xizang Plateau. Exploring the high-altitude (HA) adaptation mechanisms in Vulpes species may broaden our understanding of the genetic adaptability of species to HA environments. In this study, we constructed a high-quality chromosome-level genome for V. v. montana. The assembled genome was ~2.34 Gb and N50 length of 139.03 Mb, and 99.51% (~2.33 Gb) of the assembly was anchored into 17 pseudo-chromosomes. A total of 20,056 protein-coding genes were predicted in the assembled genome, 93.06% of which were functionally annotated. Comparative genomics analysis reveals unique and shared HA adaptation mechanisms in HA Vulpes species. Further, we identified a parallel amino acid site substitution (Serine to Phenylalanine) at position 132 in the IGSF22 gene that is present in HA Vulpes species. This mutation significantly enhances the expression of this immune-related gene under hypoxic conditions and also markedly up-regulates the expression of genes associated with angiogenesis (AKT1, ABCG2 and VEGFA). Our study reveals the molecular mechanism of HA adaptation in Vulpes species and provides a high-quality genomic resource for future research.