INRAE, Oniris, BIOEPAR, Nantes, France.
Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
BMC Genomics. 2022 Jun 23;23(1):463. doi: 10.1186/s12864-022-08669-4.
Ticks represent a major health issue for humans and domesticated animals. Exploring the expression landscape of the tick's central nervous system (CNS), known as the synganglion, would be an important step in understanding tick physiology and in managing tick-borne diseases, but studies on that topic are still relatively scarce. Neuron-specific genes like the cys-loop ligand-gated ion channels (cys-loop LGICs, or cysLGICs) are important pharmacological targets of acaricides. To date their sequence have not been well catalogued for ticks, and their phylogeny has not been fully studied.
We carried out the sequencing of transcriptomes of the I. ricinus synganglion, for adult ticks in different conditions (unfed males, unfed females, and partially-fed females). The de novo assembly of these transcriptomes allowed us to obtain a large collection of cys-loop LGICs sequences. A reference meta-transcriptome based on synganglion and whole body transcriptomes was then produced, showing high completeness and allowing differential expression analyses between synganglion and whole body. Many of the genes upregulated in the synganglion were associated with neurotransmission and/or localized in neurons or the synaptic membrane. As the first step of a functional study of cysLGICs, we cloned the predicted sequence of the resistance to dieldrin (RDL) subunit homolog, and functionally reconstituted the first GABA-gated receptor of Ixodes ricinus. A phylogenetic study was performed for the nicotinic acetylcholine receptors (nAChRs) and other cys-loop LGICs respectively, revealing tick-specific expansions of some types of receptors (especially for Histamine-like subunits and GluCls).
We established a large catalogue of genes preferentially expressed in the tick CNS, including the cysLGICs. We discovered tick-specific gene family expansion of some types of cysLGIC receptors, and a case of intragenic duplication, suggesting a complex pattern of gene expression among different copies or different alternative transcripts of tick neuro-receptors.
蜱虫对人类和家养动物的健康构成了重大威胁。探索蜱虫中枢神经系统(CNS)的表达谱,即联体神经节,对于了解蜱虫生理学和管理蜱传疾病将是重要的一步,但该领域的研究仍然相对较少。神经元特异性基因,如 cys- 环配体门控离子通道(cys- 环 LGICs,或 cysLGICs)是杀蜱剂的重要药理学靶点。迄今为止,它们在蜱虫中的序列尚未得到很好的编目,其系统发育也尚未得到充分研究。
我们对不同条件下(未进食雄性、未进食雌性和部分进食雌性)的硬蜱联体神经节进行了转录组测序。这些转录组的从头组装使我们获得了大量 cys- 环 LGICs 序列。然后生成了一个基于联体神经节和整个身体转录组的参考元转录组,显示出很高的完整性,并允许在联体神经节和整个身体之间进行差异表达分析。在联体神经节中上调的许多基因与神经传递有关,或定位于神经元或突触膜中。作为 cysLGICs 功能研究的第一步,我们克隆了抗性滴滴涕(RDL)亚基同源物的预测序列,并对 Ixodes ricinus 的第一个 GABA 门控受体进行了功能重建。分别对烟碱型乙酰胆碱受体(nAChRs)和其他 cys- 环 LGICs 进行了系统发育研究,揭示了一些类型的受体(特别是组胺样亚基和 GluCls)在蜱中的特异性扩张。
我们建立了一个在蜱虫中枢神经系统中优先表达的基因的大型目录,包括 cysLGICs。我们发现了一些类型的 cysLGIC 受体在蜱中的基因家族扩张,以及一个内含子重复的例子,这表明了不同拷贝或不同替代转录本的蜱神经受体之间存在复杂的基因表达模式。