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Animals living at high altitudes have evolved distinct phenotypic and genotypic adaptations against stressful environments. We studied the adaptive patterns of altitudinal stresses on transcriptome turnover in subterranean plateau zokors ( Myospalax baileyi ) in the high-altitude Qinghai-Tibetan Plateau. Transcriptomes of zokors from three populations with distinct altitudes and ecologies ( L ow: 2846 m,  M iddle: 3282 m,  H igh: 3,714 m) were sequenced and compared. Phylogenetic and principal component analyses classified them into three divergent altitudinal population clusters. Genetic polymorphisms showed that the population at  H , approaching the uppermost species boundary, harbors the highest genetic polymorphism. Moreover, 1056 highly up-regulated UniGenes were identified from  M  to  H . Gene ontologies reveal genes like  EPAS1  and  COX1  were overexpressed under hypoxia conditions.  EPAS1 ,  EGLN1 , and  COX1  were convergent in high-altitude adaptation against stresses in other species. The fixation indices ( F   ST   and  G   ST  )-based outlier analysis identified 191 and 211 genes, highly differentiated among  L ,  M , and  H . We observed adaptive transcriptome changes in  Myospalax baileyi , across a few hundred meters, near the uppermost species boundary, regardless of their relatively stable underground burrows’ microclimate. The highly variant genes identified in  Myospalax  were involved in hypoxia tolerance, hypercapnia tolerance, ATP-pathway energetics, and temperature changes.

Adaptive Transcriptome Profiling of Subterranean Zokor, Myospalax baileyi, to High- Altitude Stresses in Tibet