The highest-elevation frog provides insights into mechanisms and evolution of defenses against high ultraviolet radiation

Abstract Defense against increasing ultraviolet radiation (UV) exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV-defense mechanisms remains largely unexplored. Herein, we analyzed UV responses in the highest-elevation frog, Nanorana parkeri, using integrated approaches. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. Our study revealed new UV-defense systems. Genomic and metabolomic analysis along with large-scale transcriptomic and microRNA profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. Both gene mutations and expression shifts contribute to such UV adaptation. We found that microRNAs play important regulatory roles, especially in decreasing the expression levels of cell-cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Our work demonstrates a genetic framework for evolution of UV-defense in a natural environment.