高原蛙类的紫外应答机制及其抗氧化系统的适应性进化研究

With growing consumption of atmospheric ozone layer, the intensity of ultraviolet radiation (UV) increases yearly in recent years, whose effects on skin damage has became one of the main factors threatening human health. The Qinghai-Tibet Plateau (QTP) is a typical high-UV environment, endemic animals on which have acquired corresponding adaptations during their evolution. Studies on these animals' UV adaptations would give clues for the therapy of UV-induced damages. However, it remains unclear what the molecular mechanisms behind the high-elevation animals' UV resistance. As the skin of amphibians is bare, the frogs are more sensitive to the external environment, which makes them become the ideal materials for investigating the UV response mechanisms of animals. Nanorana parkeri is the absolutely dominant frog on the QTP. During our previous studies, we have sequenced and assembled its whole genome, and also observed that it has a stronger ability to resist ultraviolet (i.e. higher efficiency of scavenging free radicals). In this project, through comprehensive analyses of genome, transcriptome, and proteome between N. parkeri and its low-altitude relatives, we would explore the genetic mechanisms underlying its higher protection against UV radiation. During this, we will first decipher molecular evolutionary schemes of the antioxidant system in the high-altitude frogs, such as whether the antioxidant enzymes or small polypeptide in high-altitude frogs experienced positive selection. With further functional experiments, we would obtain some potential functional molecules (i.e. antioxidant proteins or peptides) with higher antioxidant activities. All the results obtained in this study would provide additional understanding of animals’ high-altitude adaptations, and also shed lights on the medical repairs of UV-induced skin damage.

随着大气臭氧层的消耗，地球表面的紫外线强度逐年增强，其造成的皮肤损伤等危害已成为目前威胁人类健康的主要因子之一。青藏高原作为典型的强紫外环境，其土著生物已进化出相应的适应性，对这些动物的紫外适应机制的探讨将为人类的紫外损伤医疗提供线索。由于两栖动物皮肤裸露，对外界环境敏感，成为研究动物的紫外适应机制的理想材料。其中，高山倭蛙是青藏高原蛙类的绝对优势种，同时我们前期的研究已成功破译其全基因组信息，并鉴定该物种具有更强的抵御紫外的能力。因此，本项目拟选取高山倭蛙及其近缘种为研究对象，通过系统生物学分析（转录组、蛋白质全谱，蛋白组和多肽组定量研究）和进化分析，综合探讨高原蛙类抗氧化系统（如抗氧化酶或小分子多肽等）的进化模式及其紫外适应机制；结合功能测定，系统挖掘高原蛙类抵御紫外照射的关键活性物质，在完善我们对动物高原适应机制理解的同时，为紫外损伤的医疗修复提供理论依据。

不断上升的紫外线(UV)辐射对生物体的生存是一个巨大的威胁，特别是在紫外线强烈的高海拔地区。高山倭蛙(Nanorana Parkeri)是一种极高海拔的物种，与其低海拔近亲相比，它在皮肤中暴露于更高的紫外线中，同时也进化出有效的抗氧化活性和损伤修复能力，为人们研究动物皮肤的紫外适应机制以及应对紫外辐射过程中所涉及的分子过程提供了理想模型，也为皮肤健康医学提供潜在的生物活性资源。为此，我们在前期对其染色体水平的基因组进行了测序，并进行了大规模转录组和microRNA测序的时程紫外线照射实验。我们的数据揭示了在进化中获得的遗传变异和microRNA介导的表达调控在紫外线照射后以时间依赖的方式在防御系统中相互作用：比如获得性免疫和皮肤保湿激活和诱导以下抗炎/抗氧化反应，以及渐进的热反应和对周围神经系统的保护等功能。本研究为紫外线适应背后的遗传机制的全面理解，同时也为皮肤医疗在时间尺度上的调控策略提供了新的认识。