Background Tapeworms are agents of neglected tropical diseases responsible for significant health problems and economic loss. They also exhibit adaptations to a parasitic lifestyle that confound comparisons of their development with other animals. Identifying the genetic factors regulating their complex ontogeny is essential to understanding unique aspects of their biology and for advancing novel therapeutics. Here we use RNA sequencing to identify up-regulated signalling components, transcription factors and post-transcriptional/translational regulators (genes of interest, GOI) in the transcriptomes of Larvae and different regions of segmented worms in the tapeworm Hymenolepis microstoma and combine this with spatial gene expression analyses of a selection of genes. Results RNA-seq reads collectively mapped to 90% of the > 12,000 gene models in the H. microstoma v.2 genome assembly, demonstrating that the transcriptome profiles captured a high percentage of predicted genes. Contrasts made between the transcriptomes of Larvae and whole, adult worms, and between the Scolex-Neck, mature strobila and gravid strobila, resulted in 4.5-30% of the genes determined to be differentially expressed. Among these, we identified 190 unique GOI up-regulated in one or more contrasts, including a large range of zinc finger, homeobox and other transcription factors, components of Wnt, Notch, Hedgehog and TGF-β/BMP signalling, and post-transcriptional regulators (e.g. Boule, Pumilio). Heatmap clusterings based on overall expression and on select groups of genes representing 'signals' and 'switches' showed that expression in the Scolex-Neck region is more similar to that of Larvae than to the mature or gravid regions of the adult worm, which was further reflected in large overlap of up-regulated GOI. Conclusions Spatial expression analyses in Larvae and adult worms corroborated inferences made from quantitative RNA-seq data and in most cases indicated consistency with canonical roles of the genes in other animals, including free-living flatworms. Recapitulation of developmental factors up-regulated during larval metamorphosis suggests that strobilar growth involves many of the same underlying gene regulatory networks despite the significant disparity in developmental outcomes. The majority of genes identified were investigated in tapeworms for the first time, setting the stage for advancing our understanding of developmental genetics in an important group of flatworm parasites.

中文翻译：

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全基因组转录组分析和空间表达分析可识别绦虫发育的信号和开关。


背景 绦虫是被忽视的热带疾病的病原体，造成严重的健康问题和经济损失。它们还表现出对寄生生活方式的适应，这使得它们的发育与其他动物的比较相混淆。识别调节其复杂个体发育的遗传因素对于理解其生物学的独特方面和推进新疗法至关重要。在这里，我们使用 RNA 测序来鉴定幼虫和绦虫膜壳小口线虫不同区域的转录组中上调的信号成分、转录因子和转录后/翻译调节因子（感兴趣的基因，GOI），并将其与空间选择基因的基因表达分析。结果 RNA-seq 读数共同映射到 H. microstoma v.2 基因组组装中 > 12,000 个基因模型的 90%，表明转录组图谱捕获了高比例的预测基因。对幼虫和完整成虫的转录组以及头节颈、成熟球虫和妊娠球虫的转录组进行比较，结果发现 4.5-30% 的基因被确定为差异表达。其中，我们鉴定了 190 个独特的 GOI 在一个或多个对比中上调，包括大量锌指、同源框和其他转录因子、Wnt、Notch、Hedgehog 和 TGF-β/BMP 信号传导的成分，以及转录后信号通路监管机构（例如 Boule、Pumilio）。 基于总体表达和代表“信号”和“开关”的选定基因组的热图聚类表明，头节颈区域的表达与幼虫的表达更相似，而不是与成虫的成熟或妊娠区域相似。进一步体现在上调的GOI的大量重叠上。结论 幼虫和成虫的空间表达分析证实了定量 RNA-seq 数据的推论，并且在大多数情况下表明与其他动物（包括自由生活的扁虫）中基因的典型作用一致。幼虫变态过程中发育因子上调的概括表明，尽管发育结果存在显着差异，但球状生长涉及许多相同的潜在基因调控网络。首次在绦虫中研究了所鉴定的大多数基因，为推进我们对重要的扁形虫寄生虫群体的发育遗传学的理解奠定了基础。