Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
King Abdullah University of Science and Technology, Thuwal, Makkah, Saudi Arabia.
BMC Biol. 2021 Dec 2;19(1):255. doi: 10.1186/s12915-021-01189-9.
The consequences of the earth's daily rotation have led to 24-h biological rhythms in most organisms. Even some parasites are known to have daily rhythms, which, when in synchrony with host rhythms, can optimise their fitness. Understanding these rhythms may enable the development of control strategies that take advantage of rhythmic vulnerabilities. Recent work on protozoan parasites has revealed 24-h rhythms in gene expression, drug sensitivity and the presence of an intrinsic circadian clock; however, similar studies on metazoan parasites are lacking. To address this, we investigated if a metazoan parasite has daily molecular oscillations, whether they reveal how these longer-lived organisms can survive host daily cycles over a lifespan of many years and if animal circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni that lives in the vasculature for decades and causes the tropical disease schistosomiasis.
Using round-the-clock transcriptomics of male and female adult worms collected from experimentally infected mice, we discovered that ~ 2% of its genes followed a daily pattern of expression. Rhythmic processes included a stress response during the host's active phase and a 'peak in metabolic activity' during the host's resting phase. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include predicted drug targets and a vaccine candidate. These 24-h rhythms may be driven by host rhythms and/or generated by a circadian clock; however, orthologs of core clock genes are missing and secondary clock genes show no 24-h rhythmicity.
There are daily rhythms in the transcriptomes of adult S. mansoni, but they appear less pronounced than in other organisms. The rhythms reveal temporally compartmentalised internal processes and host interactions relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other animals. We have shown which transcripts oscillate at this temporal scale and this will benefit the development and delivery of treatments against schistosomiasis.
地球的自转导致了大多数生物体的 24 小时生物节律。即使是一些寄生虫也被认为具有昼夜节律，当这些节律与宿主的节律同步时，可以优化它们的适应性。了解这些节律可能会促使开发出利用节律脆弱性的控制策略。最近对原生动物寄生虫的研究揭示了基因表达、药物敏感性和内在生物钟的 24 小时节律；然而，类似的后生动物寄生虫的研究还很缺乏。为了解决这个问题，我们研究了后生动物寄生虫是否存在每日分子波动，它们是否揭示了这些寿命较长的生物如何在宿主的每日周期中生存多年，以及是否存在动物生物钟基因和节律。我们使用生活在血管中长达几十年并导致热带病血吸虫病的人类血吸虫 Schistosoma mansoni 来解决这些问题。
通过对从实验感染的小鼠中收集的雄性和雌性成虫进行 24 小时转录组学分析，我们发现其约 2%的基因呈现出昼夜节律表达模式。节律性过程包括在宿主活动期的应激反应和在宿主休息期的“代谢活性高峰”。雌性生殖系统的转录谱与每日产卵模式相匹配（卵是宿主病理学的主要驱动因素）。以最高振幅循环的基因包括预测的药物靶点和疫苗候选物。这些 24 小时节律可能是由宿主节律驱动的，也可能是由生物钟产生的；然而，核心生物钟基因的同源物缺失，次要生物钟基因没有 24 小时节律性。
成年 S. mansoni 的转录组存在昼夜节律，但与其他生物体相比，这些节律的表现不太明显。这些节律揭示了与体内生存和宿主间传播相关的时间上分隔的内部过程和宿主相互作用。我们的研究结果表明，如果这些昼夜节律是由内在生物钟产生的，那么振荡机制必须与其他动物不同。我们已经展示了哪些转录本在这个时间尺度上波动，这将有助于开发和提供对抗血吸虫病的治疗方法。
