Data from: Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai–Tibetan Plateau in a predatory bird

Low oxygen and temperature pose key physiological challenges for endotherms living on the Qinghai–Tibetan Plateau (QTP). Molecular adaptations to high-altitude living have been detected in the genomes of Tibetans, their domesticated animals and a few wild species, but the contribution of transcriptional variation to altitudinal adaptation remains to be determined. Here we studied a top QTP predator, the saker falcon, and analysed how the transcriptome has become modified to cope with the stresses of hypoxia and hypothermia. Using a hierarchical design to study saker populations inhabiting grassland, steppe/desert and highland across Eurasia, we found that the QTP population is already distinct despite having colonized the Plateau <2000 years ago. Selection signals are limited at the cDNA level, but of only seventeen genes identified, three function in hypoxia and four in immune response. Our results show a significant role for RNA transcription: 50% of upregulated transcription factors were related to hypoxia responses, differentiated modules were significantly enriched for oxygen transport, and importantly, divergent EPAS1 functional variants with a refined co-expression network were identified. Conservative gene expression and relaxed immune gene variation may further reflect adaptation to hypothermia. Our results exemplify synergistic responses between DNA polymorphism and RNA expression diversity in coping with common stresses, underpinning the successful rapid colonization of a top predator onto the QTP. Importantly, molecular mechanisms underpinning highland adaptation involve relatively few genes, but are nonetheless more complex than previously thought and involve fine-tuned transcriptional responses and genomic adaptation.

生活在青藏高原（Qinghai–Tibetan Plateau, QTP）的恒温动物，面临着低氧与低温带来的核心生理挑战。此前已在藏族人群、家养动物及少数野生物种的基因组中，发现了针对高海拔生活的分子适应机制，但转录变异对高海拔适应的贡献仍有待阐明。本研究以青藏高原顶级捕食者——猎隼（saker falcon）为研究对象，解析其转录组如何重塑以应对低氧与低温胁迫。本研究采用分层实验设计，对欧亚大陆草原、草原/荒漠及高海拔区域的猎隼种群开展研究，结果发现，尽管猎隼种群在不到2000年前才定居青藏高原，但其种群已与其他区域种群产生显著分化。在互补DNA（cDNA）层面，选择信号较为有限；仅鉴定出17个相关基因，其中3个参与低氧应答，4个参与免疫应答。我们的研究结果揭示了RNA转录的关键作用：上调转录因子中有50%与低氧应答相关，分化模块显著富集于氧转运通路；尤为重要的是，本研究鉴定出了具有精细共表达网络的分化型内皮PAS结构域蛋白1（EPAS1）功能变异体。保守的基因表达模式与受松弛选择的免疫基因变异，可能进一步反映了猎隼对低温的适应机制。本研究结果表明，在应对共同胁迫时，DNA多态性与RNA表达多样性之间存在协同应答机制，这为顶级捕食者成功快速定居青藏高原奠定了基础。值得注意的是，支撑高海拔适应的分子机制仅涉及相对较少的基因，但其复杂程度远超此前认知，且包含精细调控的转录应答与基因组适应过程。