DataSheet1_Transcriptome analysis of pika heart tissue reveals mechanisms underlying the adaptation of a keystone species on the roof of the world.PDF

High-altitude environments impose intense stresses on living organisms and drive striking phenotypic and genetic adaptations, such as hypoxia resistance, cold tolerance, and increases in metabolic capacity and body mass. As one of the most successful and dominant mammals on the Qinghai-Tibetan Plateau (QHTP), the plateau pika (Ochotona curzoniae) has adapted to the extreme environments of the highest altitudes of this region and exhibits tolerance to cold and hypoxia, in contrast to closely related species that inhabit the peripheral alpine bush or forests. To explore the potential genetic mechanisms underlying the adaptation of O. curzoniae to a high-altitude environment, we sequenced the heart tissue transcriptomes of adult plateau pikas (comparing specimens from sites at two different altitudes) and Gansu pikas (O. cansus). Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed genes (DEGs) and their primary functions. Key genes and pathways related to high-altitude adaptation were identified. In addition to the biological processes of signal transduction, energy metabolism and material transport, the identified plateau pika genes were mainly enriched in biological pathways such as the negative regulation of smooth muscle cell proliferation, the apoptosis signalling pathway, the cellular response to DNA damage stimulus, and ossification involved in bone maturation and heart development. Our results showed that the plateau pika has adapted to the extreme environments of the QHTP via protection against cardiomyopathy, tissue structure alterations and improvements in the blood circulation system and energy metabolism. These adaptations shed light on how pikas thrive on the roof of the world.

高海拔环境对生物施加极强的环境胁迫，并推动其演化出显著的表型与遗传适应性特征，例如低氧耐受、耐寒能力提升，以及代谢水平与体重的增加。作为青藏高原（Qinghai-Tibetan Plateau, QHTP）上最为成功且占据生态主导地位的哺乳类类群之一，高原鼠兔（Ochotona curzoniae）已适应该区域极高海拔的极端环境，展现出耐寒与耐低氧的特性，这与其栖息于周边高山灌丛或森林的近缘物种形成鲜明对比。为探究高原鼠兔适应高海拔环境的潜在遗传机制，本研究对成年高原鼠兔（采集自两个不同海拔位点的样本）与甘肃鼠兔（Ochotona cansus）的心脏组织转录组进行测序。通过差异表达分析（Differential Expression Analysis）与加权基因共表达网络分析（Weighted Gene Co-expression Network Analysis, WGCNA），我们筛选出差异表达基因（Differentially Expressed Genes, DEGs）并解析其主要功能。本研究鉴定出与高海拔适应相关的关键基因及调控通路。除信号转导、能量代谢与物质运输等核心生物学过程外，高原鼠兔的差异表达基因还显著富集于平滑肌细胞增殖负调控、细胞凋亡信号通路、DNA损伤刺激的细胞应答，以及参与骨骼成熟与心脏发育的骨化作用等生物学通路。本研究结果表明，高原鼠兔通过心肌保护、组织结构重塑、血液循环系统功能优化与能量代谢水平提升，适应了青藏高原的极端环境。这些适应性特征揭示了鼠兔类群何以在‘世界屋脊’繁衍生息。