Integrated analysis of transcriptome and metabolome data reveals insights for molecular mechanisms in overwintering Tibetan frogs, .

(Anura, Dicroglossidae) is a unique frog living at high altitude on the Tibetan plateau where they must endure a long winter dormancy at low temperatures without feeding. Here, we presented a comprehensive transcriptomic and metabolomic analysis of liver tissue from summer-active overwintering , providing the first broad analysis of altered energy metabolism and gene expression in this frog species. We discovered that significantly up-regulated genes (2,397) in overwintering frogs mainly participated in signal transduction and immune responses, phagosome, endocytosis, lysosome, and autophagy, whereas 2,169 down-regulated genes were mainly involved in metabolic processes, such as oxidation-reduction process, amino acid metabolic process, fatty acid metabolic process, and TCA cycle. Moreover, 35 metabolites were shown to be differentially expressed, including 22 down-regulated and 13 up-regulated in winter. These included particularly notable reductions in the concentrations of most amino acids. These differentially expressed metabolites were mainly involved in amino acid biosynthesis and metabolism. To sum up, these findings suggest that gene expression and metabolic processes show adaptive regulation in overwintering , that contributes to maintaining homeostasis and enhancing protection in the hypometabolic state. This study has greatly expanded our understanding of the winter survival mechanisms in amphibians.