张亚平院士组Scientific Reports揭示遗传新机制

　　

　　高原鼢鼠（Myospalax baileyi）是青藏高原的土著啮齿类物种之一，它们普遍栖息于地下约1.5～2米深的密闭洞穴中。经过长期的自然选择，高原鼢鼠已经对青藏高原这种特殊环境（高海拔洞穴缺氧）表现出极强的适应性。例如：其血液中红细胞数目以及血红蛋白含量明显多于同域生存的其它物种（例如：鼠兔（Ochotona curzniae）和大鼠（Rattus norvegicus））、动脉血的氧分压约是同域生存的鼠兔和大鼠的1.5倍以及高效的肺气扩散能力等等。这些生理现象暗示了高原鼢鼠拥有强的从低氧-高碳酸环境中获取氧气的能力。然而，目前对高原鼢鼠的高原适应性进化遗传机制研究甚少。

　　中国科学院副院长、中国科学院院士、中国科学院昆明动物研究所研究员张亚平课题组对高原鼢鼠进行了深度转录组测序，利用比较基因组学手段在序列层面上来揭示高原鼢鼠高海拔洞道适应性进化遗传机制。研究结果表明，从高原鼢鼠和大鼠的最近共同祖先分歧以来，虽然高原鼢鼠在全基因组水平上表现出慢的平均进化速率（相比于大鼠），但是一些能量代谢相关基因在高原鼢鼠中发生了快速进化。同时，该研究筛选到一个特异性的GO功能类群（respiratory gaseous exchange）在高原鼢鼠的正选择基因中显著富集，这些基因可能对高原鼢鼠呼吸系统的进化具有重要作用。此外，高原鼢鼠和裸鼹鼠趋同/平行进化的基因被显著富集在某些特殊的功能类群（例如：response to hypoxia 和oxygen homeostasis），而这些重要的功能类群基因明显和高原适应相关。该研究在序列水平上探讨了高原鼢鼠的高海拔洞道缺氧适应机制，从而为全面理解整个哺乳类的高原适应性进化遗传机制提供了重要的补充材料。

　　该研究成果于近期在线发表在Scientific Reports 上，昆明动物所博士研究生邵永为第一作者，张亚平为通讯作者，该研究得到国家自然科学基金的资助。

原文摘要：
Genetic adaptations of the plateau zokor in high-elevation burrows

The plateau zokor (Myospalax baileyi) spends its entire life underground in sealed burrows. Confronting limited oxygen and high carbon dioxide concentrations, and complete darkness, they epitomize a successful physiological adaptation. Here, we employ transcriptome sequencing to explore the genetic underpinnings of their adaptations to this unique habitat. Compared to Rattus norvegicus, genes belonging to GO categories related to energy metabolism (e.g. mitochondrion and fatty acid beta-oxidation) underwent accelerated evolution in the plateau zokor. Furthermore, the numbers of positively selected genes were significantly enriched in the gene categories involved in ATPase activity, blood vessel development and respiratory gaseous exchange, functional categories that are relevant to adaptation to high altitudes. Among the 787 genes with evidence of parallel evolution, and thus identified as candidate genes, several GO categories (e.g. response to hypoxia, oxygen homeostasis and erythrocyte homeostasis) are significantly enriched, are two genes, EPAS1 and AJUBA, involved in the response to hypoxia, where the parallel evolved sites are at positions that are highly conserved in sequence alignments from multiple species. Thus, accelerated evolution of GO categories, positive selection and parallel evolution at the molecular level provide evidences to parse the genetic adaptations of the plateau zokor for living in high-elevation burrows.