西北干旱荒漠区利什曼原虫、白蛉和蜥蜴的协同进化研究

Coevolution is a hot topic in evolutionary biology. Parasites and their hosts are a special interaction system, representing an excellent system for studying coevolution. The manifestation of coevolution between them is revealed mainly in the host-specificity, coadaptation and cospeciation. Leishmaniasis is serious threat to global health and security, casued by the protozoan Leishmania spp. and transmitted via the bite of infected female sandflies. In the current context of worldwide re-emergence and spreading of leishmaniasis, the relevance of distinction of strains further gains importance. Most Chinese natural foci of leishmaniasis are located in the arid desert region in Northwest China. In a previous study based on ITS1 sequences, we found evidence for natural infection of some desert lizards in Northwest China with reptilian Leishmania and mammalian Leishmania species. Further studies on coevolution between the Leishmania parasites with their lizard hosts and sandfly vectors are recommended for a better understanding of their epidemiological involvement. In the present study, we propose to integrate genetic, epidemiological, and environmental data into investigating the coevolution between Leishmania parasites, sandflies and lizard hosts throughout the arid desert region. In order to detect the presence of Leishmania spp. in desert lizards, we will employ approaches including the traditional method of blood smear analysis and the highly sensitive polymerase chain reaction (PCR). The DNA sequences will be used for genealogical analyses in conjunction with some representative Leishmania sequences retrieved from GenBank. To identify the effects of the processes that shape parasite diversity, we will incorporate both deep (phylogenetic) and shallow (population) perspectives. We will also incorporate DNA data, climatic and geographical features into investigating the diversification, historical demography of Leishmania species. Specifically, we will conduct cophylogenetic analyses by using both event-based and distance-based approachs. The results of this study will enhance our understanding of the diversity of Leishmania parasites in lizards and their distribution range as well as the role that the lizards play in spreading leishmaniasis, and provide a good model for coevolution of parasite-host. This is crucial for correct diagnosis and prognosis of the diseases as well as for making decisions regarding treatment and control strategies. Using integrative approaches to study coevolution between parasites and their hosts is just beginning and has attracted substantial attention. This project builds on top of our previous work and will strengthen our position as a leader in this area.

协同进化是进化生物学研究的热点。寄生虫与宿主是一个特殊的互作系统，是研究协同进化的极佳体系。利什曼病对人体危害严重，由利什曼原虫引起和白蛉传播，在全球范围再度回升。西北干旱荒漠区为我国利什曼病的主要疫区，我们前期研究发现蜥蜴可寄生有蜥蜴利什曼原虫和哺乳类利什曼原虫。本项目拟对干旱荒漠区的蜥蜴、白蛉进行广泛采样，检测其体内寄生利什曼原虫的感染情况，研究利什曼原虫多样性；并整合遗传数据、流行病学特征和环境地理分布等数据，从系统发育和种群分化二个视角，重建其系统进化关系和演化历史，进而探究利什曼原虫、白蛉、蜥蜴三者之间的协同进化机制。研究结果将促进利什曼原虫的系统分类和流行病学研究，为研究寄生虫与宿主的协同进化提供良好的模型，并为理解利什曼病的传播、诊断和预警提供科学依据。用整合方法研究寄生虫与宿主的协同进化关系是近年来兴起的，我们已有很好的基础。本项目将进一步深化和强化我们在这个领域的研究。

利什曼病对人体危害严重，由利什曼原虫引起和白蛉传播。西北干旱荒漠区为我国利什曼病的主要疫区，我们前期研究发现蜥蜴可寄生有蜥蜴利什曼原虫和哺乳类利什曼原虫。我们对西北干旱荒漠区的爬行动物（蜥蜴、蛇）进行扩大采样，联合多基因片段检测了它们体内寄生利什曼原虫的感染情况。由于新冠疫情影响，野外科考进展不顺利、多次中断，未能成功地采集到白蛉。结果支持多种蜥蜴和蛇类血液不仅有蜥蜴类利什曼原虫，还有哺乳类利什曼原虫（如热带利什曼原虫、都兰利什曼原虫、杜氏利什曼原虫合体等）。干旱荒漠区利什曼原虫组成复杂、异质性高，这些寄生虫没有显著的地理结构和宿主特异性，可能与蜥蜴和白蛉不存在关联进化。中国分布的杜氏利什曼原虫复合体不是通过丝绸之路从欧洲引入，而是具有本土特点。依托本项目，我们还开展了下列相关研究：干旱荒漠区蜥蜴体表寄生蜱调查与分子鉴定；杜氏利什曼原虫的4种蛋白的生物信息分析，以寻找疫苗表位和药物靶点；内脏利什曼原虫药敏试验；婴儿利什曼原虫磷酸烯醇丙酮酸羧基酶优势表位基因；肠道菌群失调对内脏利什曼病感染致病性的影响；TLR-2 增强剂对利什曼原虫感染BALB/c小鼠致病性的影响；营养不良对内脏利什曼病感染BALB/c小鼠的致病性影响研究。此外，我们从干旱荒漠区寄生麻蜥的蜱虫样品检测到利什曼原虫DNA，这一发现暗示了蜱虫有可能参与了荒漠型黑热病的传播。依托本项目，已发表标注论文13篇，其中SCI收录10篇（第一标注论文1篇，第二标注论文2篇）；并培养中青年学术带头人1人，项目主持人先后竞聘为硕士生导师、博士生导师，1名主研人员竞聘为副教授和硕士生导师。