AbstractThe plateau zokor (Myospalax baileyi) spends its entire life underground in sealed burrows. Confronting limited oxygen and high carbon dioxide concentrations and complete darkness, they epitomize a successful physiological adaptation. Here, we employ transcriptome sequencing to explore the genetic underpinnings of their adaptations to this unique habitat. Compared toRattus norvegicus, genes belonging to GO categories related to energy metabolism (e.g. mitochondrion and fatty acid beta-oxidation) underwent accelerated evolution in the plateau zokor. Furthermore, the numbers of positively selected genes were significantly enriched in the gene categories involved in ATPase activity, blood vessel development and respiratory gaseous exchange, functional categories that are relevant to adaptation to high altitudes. Among the 787 genes with evidence of parallel evolution and thus identified as candidate genes, several GO categories (e.g. response to hypoxia, oxygen homeostasis and erythrocyte homeostasis) are significantly enriched, are two genes,EPAS1andAJUBA, involved in the response to hypoxia, where the parallel evolved sites are at positions that are highly conserved in sequence alignments from multiple species. Thus, accelerated evolution of GO categories, positive selection and parallel evolution at the molecular level provide evidences to parse the genetic adaptations of the plateau zokor for living in high-elevation burrows.