中国科学院昆明动物研究所机构知识库

适应是生物进化的核心，自达尔文时期开始就备受人们关注，物种不管是对自然选择的适应还是对人工选择的适应，其目的都是为了生存和繁衍。家养动物作为一类特殊的群体，成为学者们青睐的研究对象，对家养动物的研究不仅能了解人工选择下动物的进化过程, 而且有助于开展家养动物的选育及遗传多样性保护。那些生存在极端环境下的家养动物则既经历了人工选择作用，也经历了对自然选择的适应。家养动物的驯化推动了人类生活方式的转变，在人类现代文明的发展历程中具有非常重要的意义。随着二代测序技术的飞速发展，极大程度的推动了生物学领域的前进，也为群体遗传学的研究提供了前所未有的机遇。本论文充分利用二代测序获得的全基因组和转录组数据，以褐家鼠和实验大鼠作为人工选择的研究对象，以藏野驴和藏家驴作为家养动物高原适应的研究对象，利用群体遗传学和比较基因组学方法，结合生物学实验，从两个不同的侧面揭示家养动物的适应性进化。我们从群体遗传学角度和计算生物学角度揭示了褐家鼠的东亚南部起源，并描绘了其从起源地往东亚北部以及欧洲/非洲/中东的两条主要扩散路线。对其迁出时间进行的推断显示：褐家鼠在~173,000年前从东亚南部迁往东亚北部；在~3,100年前，由东亚南部往中东迁徙，紧接着在~2,000年前往非洲迁徙，~1,800年前迁往欧洲。这推翻了人们之前认为褐家鼠起源于东亚北部的这一假说。同时，在褐家鼠的迁徙过程中，很多与免疫系统相关的基因受到了快速进化。实验大鼠作为一种广泛使用的模式动物，由野生褐家鼠驯化而来,也是一种家养动物。与其野生祖先褐家鼠相比，实验大鼠在形态、行为及生理方面发生了很大的变化，然而实验大鼠的起源以及导致其被驯化成功的机制尚不清楚。我们通过将不同地区野生褐家鼠与不同品系实验大鼠基因组之间一系列的分析发现大量神经系统基因在大鼠驯化过程中受到人工选择作用，例如在学习记忆方面起重要作用的FOXP2和B3GAT1基因，以及节律相关基因CLOCK。有意思的是这些基因在实验大鼠的神经组织中表达水平显著上调，有助于提高学习记忆能力。我们的研究推测学习记忆能力的提高可能是导致实验大鼠被成功驯化的关键。与身体的其他部分相比，大脑是比较高能耗的组织，实验大鼠学习能力的提升固然会导致更高的能量消耗，基于转录组分析及qPCR数据揭示能量代谢相关基因在实验大鼠大脑组织中显著上调，这些都为我们进一步揭示实验大鼠的起源以及驯化的遗传机制奠定了良好的基础。居住在青藏高原的恒温动物通常有非常强的心肺功能，它们拥有更大的心脏和肺。为了解析家驴在迁徙过程中如何适应当地的环境，以及西藏野驴是否对走出非洲的家驴的遗传组分有贡献,我们从头组装了一个藏野驴的基因组，并重测序了5个藏野驴以及来自多个国家的共93个家驴的基因组。比较基因组及群体基因组学分析发现藏野驴在适应高原环境的过程中，一些与高原适应相关的基因发生了一定程度的快速进化，例如EP300，BMP10，MCTP2等。群体分化的全基因组扫描，找到了一些可能与西藏家驴高原适应相关的正选择基因，基因富集分析发现，EGLN3、EIF4E2、EIF4E2、EGLN1和SERPINE1富集于HIF-1 signaling通路中，揭示了藏家驴高原适应的潜在分子机制。同时，基因交流分析显示，藏野驴与藏家驴之间遗传组分的交流比例虽然低，但我们仍然发现EPAS1基因在藏野驴和藏家驴间存在一定程度基因交流，这很可能是西藏家驴对高海拔适应的快速机制。这些结果将有助于我们深入了解藏野驴与藏家驴之间的关系，并揭示两个物种高原适应的进化历程。 

Adaptation is the core of biological evolution, people pay close attention to it since Charles Darwin. Species adaptation to natural selection and artificial selection, is for the purpose of survival and reproduction. Domestic animals as a kind of special population, has become the favored object of researchers. The study of domestic animals can not only help us to understand the evolution of animals under artificial selection, but also help to carry out the breeding of domestic animals, and protection of genetic diversity. Those who live in extreme environments have experienced both artificial selection and natural selection. Domestication of animals facilitates the conversion of the human life style and is of great significance in the development of modern civilization. With the rapid development of the next generation sequencing technology, the progress of biology have been greatly promoted, and the research on population genetics meet unprecedented opportunities. This paper make good use of the whole genome and transcriptome data from next generation sequencing, with brown rats and laboratory rats as the research object of artificial selection, kiang and Tibetan donkey as the research object of adaption to high altitude. Using methods of population genetics and comparative genomics, combined with biology experiment, to reveal the adaptive evolution mechanism of domestic animals.We revealed a southern East Asia origin of the brown rat in perspective of population genetics and computational biology, and described its dispersal route from the origin to northern East Asia and Europe/Middle East/Africa respectively. The inferring showed that brown rat out of southern East Asia to northern East Asia by ~173,000 years ago; to Middle East by ~3,100 years ago, following to Africa by ~2,000 years ago, then to Europe by ~1,800 years ago. This inconsistent with the hypothesis that the brown rat originated in northern East Asia. At the same time, many genes associated with the immune system have evolved rapidly during the migration.The laboratory rat, which has been widely used in biomedical research as an animal model, is commonly believed to be domesticated from wild brown rat. Compared to their wild ancestors, laboratory rats exhibit different morphological, physiological and behavioral attributes. However, the genetic mechanisms underlying these phenotypic differences remain elusive. Based on methods of population genetics and compared to wild brown rat, many genes involved in the nervous system, particularly FOXP2, B3GAT1 and CLOCK, have evolved under artificial selection in the laboratory rat, and expression level of these genes were significantly up-regulated in the nervous tissue of laboratory rat. These changes likely enhanced the learning ability and regulation of circadian rhythm to promote successful domestication of laboratory rat. Brain functions are quite energy intensive relative to the rest of the body, enhanced learning ability in the laboratory rats likely placed additional energy demands. As expected, many genes responsible for energy metabolism including mitochondrial genes exhibited a substantially increased expression in the brain of laboratory rats compared with wild rats. These findings will be helpful for understanding the origin and evolution of the laboratory rats as well as the process of domestication.Warm-blooded animals living on the Qinghai-Tibet Plateau usually have very strong heart and lung functions, and they have larger hearts and lungs. In order to explore how donkey adapt to the local environment in the process of migration, and whether kiang provide genetic component to Tibetan donkey during the process of migration. We provided a de novo genome of kiang, as well as 98 re-sequenced genomes including 5 kiangs and 93 domestic donkeys across the world. We revealed some rapidly evolved genes (e.g. EP300, BMP10, MCTP2, etc.) underlying high altitude adaptation of kiang. Genome-wide scanning of population differentiation showing that some genes may be related to high altitude adaptation of Tibetan donkey. Gene Ontology analysis found that EGLN3, EIF4E2, EIF4E2, EGLN1 and SERPINE1 enriched in HIF - 1 signaling pathways, revealed the molecular mechanisms of high altitude adaptation. However, the extension of admixture between kiang and domestic donkey is very low. Signature of genetic migration of EPAS1 was recapitulated from kiang to Tibetan domestic donkeys, likely facilitating high altitude adaptation of domestic donkey. The data resource and results generated in the present study will provide insight into the scenarios of relationship between kiang and domestic donkey, and their evolution.