Comparative analysis of peripheral blood reveals transcriptomic adaptations to extreme environments on the Qinghai-Tibetan Plateau in the gray wolf (Canis lupus chanco)

Abstract

Molecular adaptations to life on the Qinghai-Tibetan Plateau (QTP) have been detected in the genomes of many native animals, but the contribution of variations in gene expression to high-altitude adaptation remains to be determined. Here, we sequenced the peripheral blood transcriptomes of the lowland wolf and the Tibetan wolf (Canis lupus chanco), an endemic top predator on the QTP, and analyzed how the gene expression pattern has become modified to cope with the extreme plateau environments. Comparisons of the transcriptomes of Tibetan wolves and their lowland counterparts revealed 90 differentially expressed genes (DEGs), including 6 genes (ATP6, ATP8, COX3, CYTB, ND2, and ND4) located in the mitochondrial respiratory chain. Several DEGs are functionally involved in DNA repair (RAD52 and NUPR1), reactive oxygen species (ROS) regulation (GSTP1 and RETSAT), and cardiovascular homeostasis (ACTA2, CD151, DDX6, HPSE, and YOD1). Further functional enrichment analyses demonstrated that the identified DEGs were significantly enriched in specific functional categories related to energy metabolism, hypoxic response, and cardiovascular homeostasis, indicating that the gene expression variation in Tibetan wolves may contribute to their adaptation to life on the QTP. The phylogenetic topology of worldwide populations based on 12 mitochondrial protein-coding genes (MPGs) is inconsistent with the patterns revealed by a previous genome-wide study, implying that adaptive evolution may have occurred in the MPGs of Tibetan wolves. Wolf ATP8 was shown to have a higher dN/dS (ω) ratio (ω = 0.712) than the other 11 genes (ω ≤ 0.272). Overall, our study provides new insights into the mechanisms underlying high-altitude adaptations in a wild carnivore with not only mitochondrial gene adaptation but also fine-tuned gene expression responses.