背景:血吸虫病是一种被忽视的热带病,困扰着全世界数百万人;它是由血吸虫引起的,唯一具有ZW系统的雌雄异株吸虫。日本血吸虫是亚洲特有的;日本血吸虫的Z染色体占整个基因组的四分之一。使用重测序数据检测阳性选择以了解适应性进化已应用于各种病原体,包括日本血吸虫.然而,Z染色体对进化和适应的贡献往往被忽视。
方法:我们公开使用重新测序数据在72个日本血吸虫的Z染色体上获得了1,077,526个高质量的SNP。要检查更快的Z效应,我们比较了日本血吸虫与两个密切相关的物种的序列差异,血吸虫和曼氏血吸虫。通过计算核苷酸多样性(π)和Dxy值,比较了日本血吸虫Z染色体和常染色体之间的遗传多样性。还基于PCA和结构分析评估了种群结构。此外,我们采用了多种方法,包括田岛的D,FST,iHS,XP-EHH,和CMS检测Z染色体上的阳性选择信号。进行进一步的RNAi敲除实验以研究候选基因的潜在生物学功能。
结果:我们的研究发现,日本血吸虫的Z染色体比常染色体进化更快,遗传差异更明显,虽然影响可能小于基因间的变异。与常染色体相比,日本血吸虫的Z染色体具有更明显的亚群遗传差异。值得注意的是,我们确定了一组与宿主-寄生虫共同进化相关的候选基因.特别是,LCAT在台湾人群中表现出明显的选择信号。进一步的RNA干扰实验表明,LCAT对于日本血吸虫在确定宿主中的存活和繁殖是必需的。此外,我们确定了几个与C-M群体中中间宿主特异性相关的基因,包括Rab6和VCP,参与对宿主的适应性免疫逃避。
结论:我们的研究为日本血吸虫Z染色体的适应性进化提供了有价值的见解,并进一步促进了我们对这种医学上重要的寄生虫及其宿主的共同进化的理解。
BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected.
METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima\'s D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes.
RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host.
CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.