Daily rhythms in gene expression of the human parasite Schistosoma mansoni

Abstract Background 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. Results 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. Conclusions 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.

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Daily rhythms in the transcriptomes of the human parasite Schistosoma mansoni

10.1101/2021.04.21.440693 ◽

2021 ◽

Author(s):

Kate A. Rawlinson ◽

Adam J. Reid ◽

Zhigang Lu ◽

Patrick Driguez ◽

Anna Wawer ◽

...

Keyword(s):

Schistosoma Mansoni ◽

Clock Genes ◽

Biological Rhythms ◽

Daily Rhythms ◽

Night Time ◽

Time Stress ◽

Blood Flukes ◽

Diel Cycles ◽

Oscillatory Mechanism ◽

Insight Into

AbstractThe consequences of the earth’s daily rotation have led to 24-hour biological rhythms in most organisms. Parasites have daily rhythms, which, when in synchrony with host rhythms, optimize their fitness. Using round-the-clock transcriptomics of male and female Schistosoma mansoni blood flukes we have discovered the first 24-hour molecular oscillations in a metazoan parasite, and gained insight into its daily rhythms. We show that expression of ∼2% of its genes followed diel cycles. Rhythmic processes, in synchrony in both sexes, included a night-time stress response and a day-time metabolic ‘rush hour’. These 24hr rhythms may be driven by host rhythms and/or generated by an intrinsic circadian clock. However, canonical core clock genes are lacking, suggesting an unusual oscillatory mechanism or loss of a functional clock. The daily rhythms in biology identified here, may promote within-host survival and between-host transmission, and are important for the development and delivery of therapeutics against schistosomiasis.

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Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars

BMC Genomics ◽

10.1186/s12864-021-07869-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yanlei Yue ◽

Ze Jiang ◽

Enoch Sapey ◽

Tingting Wu ◽

Shi Sun ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Chromosome Structure ◽

Clock Genes ◽

Expression Profiles ◽

Circadian Rhythmicity ◽

Rna Seq ◽

Night Time ◽

Time Points ◽

Circadian Clock Genes

Abstract Background In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear. Results We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean. Conclusions These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

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Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development

10.1101/757633 ◽

2019 ◽

Cited By ~ 3

Author(s):

Arporn Wangwiwatsin ◽

Anna V. Protasio ◽

Shona Wilson ◽

Christian Owusu ◽

Nancy E. Holroyd ◽

...

Keyword(s):

Gene Expression ◽

Schistosoma Mansoni ◽

Chronic Infection ◽

Egg Laying ◽

Mammalian Host ◽

Expression Data ◽

Mammalian Development ◽

Host Parasite Interactions ◽

Parasitic Flatworm ◽

Host Parasite

AbstractSchistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host–parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.Author SummaryThe life cycle of the parasitic flatworm Schistosoma mansoni is split between snail and mammalian (often human) hosts. An infection can last for more than 10 years, during which time the parasite physically interacts with its mammalian host as it moves through the bloodstream, travelling through the lungs and liver, to eventually establish a chronic infection in the blood vessels around the host gut. Throughout this complex journey, the parasite develops from a relatively simple larval form into a more complex, sexually reproducing adult. To understand the molecular basis of parasite interactions with the host during this complex journey we have produced genome-wide expression data from developing parasites. The parasites were collected from experimentally-infected mice over its developmental time-course from the poorly studied lung stage, to the fully mature egg-laying adult worm. The data highlight many genes involved in processes known to be associated with key stages of the infection. In addition, the gene expression data provide a unique view of interactions between the parasite and the immune system in the lung, including novel players in host-parasite interactions. A detailed understanding of these processes may provide new opportunities to design intervention strategies, particularly those focussed on the early stages of the infection that are not targeted by current chemotherapy.

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The Circadian Clock inArabidopsisRoots Is a Simplified Slave Version of the Clock in Shoots

Science ◽

10.1126/science.1161403 ◽

2008 ◽

Vol 322 (5909) ◽

pp. 1832-1835 ◽

Cited By ~ 156

Author(s):

Allan B. James ◽

José A. Monreal ◽

Gillian A. Nimmo ◽

Ciarán L. Kelly ◽

Pawel Herzyk ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Circadian Clock ◽

Clock Genes ◽

Plant Cells ◽

Feedback Loops ◽

Circadian Oscillator ◽

Inhibit Gene Expression ◽

Organ Specific ◽

Plant Clock

The circadian oscillator in eukaryotes consists of several interlocking feedback loops through which the expression of clock genes is controlled. It is generally assumed that all plant cells contain essentially identical and cell-autonomous multiloop clocks. Here, we show that the circadian clock in the roots of matureArabidopsisplants differs markedly from that in the shoots and that the root clock is synchronized by a photosynthesis-related signal from the shoot. Two of the feedback loops of the plant circadian clock are disengaged in roots, because two key clock components, the transcription factors CCA1 and LHY, are able to inhibit gene expression in shoots but not in roots. Thus, the plant clock is organ-specific but not organ-autonomous.

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Latitudinal clines: an evolutionary view on biological rhythms ,

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2013.0433 ◽

2013 ◽

Vol 280 (1765) ◽

pp. 20130433 ◽

Cited By ~ 109

Author(s):

Roelof A. Hut ◽

Silvia Paolucci ◽

Roi Dor ◽

Charalambos P. Kyriacou ◽

Serge Daan

Keyword(s):

Circadian Clock ◽

Clock Genes ◽

Biological Rhythms ◽

Review Literature ◽

Selection Pressures ◽

Circadian Clock Genes ◽

Evolutionary View ◽

Selective Forces ◽

Latitudinal Clines

Properties of the circadian and annual timing systems are expected to vary systematically with latitude on the basis of different annual light and temperature patterns at higher latitudes, creating specific selection pressures. We review literature with respect to latitudinal clines in circadian phenotypes as well as in polymorphisms of circadian clock genes and their possible association with annual timing. The use of latitudinal (and altitudinal) clines in identifying selective forces acting on biological rhythms is discussed, and we evaluate how these studies can reveal novel molecular and physiological components of these rhythms.

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SPF45-related splicing factor for phytochrome signaling promotes photomorphogenesis by regulating pre-mRNA splicing in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1706379114 ◽

2017 ◽

Vol 114 (33) ◽

pp. E7018-E7027 ◽

Cited By ~ 18

Author(s):

Ruijiao Xin ◽

Ling Zhu ◽

Patrice A. Salomé ◽

Estefania Mancini ◽

Carine M. Marshall ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Molecular Mechanisms ◽

Fluorescent Protein ◽

Clock Genes ◽

Mrna Processing ◽

Mrna Splicing ◽

Splicing Factor ◽

Light Signaling ◽

Small Nuclear Ribonucleoprotein

Light signals regulate plant growth and development by controlling a plethora of gene expression changes. Posttranscriptional regulation, especially pre-mRNA processing, is a key modulator of gene expression; however, the molecular mechanisms linking pre-mRNA processing and light signaling are not well understood. Here we report a protein related to the human splicing factor 45 (SPF45) named splicing factor for phytochrome signaling (SFPS), which directly interacts with the photoreceptor phytochrome B (phyB). In response to light, SFPS-RFP (red fluorescent protein) colocalizes with phyB-GFP in photobodies. sfps loss-of-function plants are hyposensitive to red, far-red, and blue light, and flower precociously. SFPS colocalizes with U2 small nuclear ribonucleoprotein-associated factors including U2AF65B, U2A′, and U2AF35A in nuclear speckles, suggesting SFPS might be involved in the 3′ splice site determination. SFPS regulates pre-mRNA splicing of a large number of genes, of which many are involved in regulating light signaling, photosynthesis, and the circadian clock under both dark and light conditions. In vivo RNA immunoprecipitation (RIP) assays revealed that SFPS associates with EARLY FLOWERING 3 (ELF3) mRNA, a critical link between light signaling and the circadian clock. Moreover, PHYTOCHROME INTERACTING FACTORS (PIFs) transcription factor genes act downstream of SFPS, as the quadruple pif mutant pifq suppresses defects of sfps mutants. Taken together, these data strongly suggest SFPS modulates light-regulated developmental processes by controlling pre-mRNA splicing of light signaling and circadian clock genes.

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Changes in ambient temperature are the prevailing cue in determining Brachypodium distachyon diurnal gene regulation

10.1101/762021 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kirk J-M. MacKinnon ◽

Benjamin J. Cole ◽

Chang Yu ◽

Joshua H. Coomey ◽

Nolan T. Hartwick ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Circadian Clock ◽

Clock Genes ◽

Brachypodium Distachyon ◽

Regulation Of Gene Expression ◽

Enrichment Analysis ◽

Grass Species ◽

List Type ◽

Sequence Motifs

SUMMARYPlants are continuously exposed to diurnal fluctuations in light and temperature, and spontaneous changes in their physical or biotic environment. The circadian clock coordinates regulation of gene expression with a 24-hour period, enabling the anticipation of these events.We used RNA sequencing to characterize the Brachypodium distachyon transcriptome under light and temperature cycles, as well as under constant conditions.Approximately 3% of the transcriptome was regulated by the circadian clock, a smaller proportion reported in most other species. For most transcripts that were rhythmic under all conditions, including many known clock genes, the period of gene expression lengthened from 24 to 27 h in the absence of external cues. To functionally characterize the cyclic transcriptome in B. distachyon, we used Gene Ontology enrichment analysis, and found several terms significantly associated with peak expression at particular times of the day. Furthermore we identified sequence motifs enriched in the promoters of similarly-phased genes, some potentially associated with transcription factors.When considering the overlap in rhythmic gene expression and specific pathway behavior, thermocycles was the prevailing cue that controlled diurnal gene regulation. Taken together, our characterization of the rhythmic B. distachyon transcriptome represents a foundational resource with implications in other grass species.

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Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms

10.1101/2020.10.09.333732 ◽

2020 ◽

Author(s):

Yangbo Xiao ◽

Ye Yuan ◽

Mariana Jimenez ◽

Neeraj Soni ◽

Swathi Yadlapalli

Keyword(s):

Gene Expression ◽

Circadian Rhythms ◽

Nuclear Envelope ◽

Circadian Clock ◽

Clock Genes ◽

Circadian Clocks ◽

Spatiotemporal Organization ◽

Clock Proteins ◽

Expression Behavior ◽

Clock Protein

ABSTRACTCircadian clocks regulate ∼24 hour oscillations in gene expression, behavior, and physiology. While the molecular and neural mechanisms of circadian rhythms are well characterized, how cellular organization of clock components controls circadian clock regulation remains poorly understood. Here, we elucidate how clock proteins regulate circadian rhythms by controlling the spatiotemporal organization of clock genes. Using high-resolution live imaging techniques we demonstrate that Drosophila clock proteins are concentrated in a few discrete foci and are organized at the nuclear envelope; these results are in contrast to longstanding expectations that clock proteins are diffusely distributed in the nucleus. We also show that clock protein foci are highly dynamic and change in number, size, and localization over the circadian cycle. Further, we demonstrate that clock genes are positioned at the nuclear periphery by the clock proteins precisely during the circadian repression phase, suggesting that subnuclear localization of clock genes plays an important role in the control of rhythmic gene expression. Finally, we show that Lamin B receptor, a nuclear envelope protein, is required for peripheral localization of clock protein foci and clock genes and for normal circadian rhythms. These results reveal that clock proteins form dynamic nuclear foci and play a hitherto unexpected role in the subnuclear reorganization of clock genes to control circadian rhythms, identifying a novel mechanism of circadian regulation. Our results further suggest a new role for clock protein foci in the clustering of clock-regulated genes during the repression phase to control gene co-regulation and circadian rhythms.SIGNIFICANCEAlmost all living organisms have evolved circadian clocks to tell time. Circadian clocks regulate ∼24-hour oscillations in gene expression, behavior and physiology. Here, we reveal the surprisingly sophisticated spatiotemporal organization of clock proteins and clock genes and its critical role in circadian clock function. We show, in contrast to current expectations, that clock proteins are concentrated in a few discrete, dynamic nuclear foci at the nuclear envelope during the repression phase. Further, we uncovered several unexpected features of clock protein foci, including their role in positioning the clock genes at the nuclear envelope precisely during the repression phase to enable circadian rhythms. These studies provide fundamental new insights into the cellular mechanisms of circadian rhythms and establish direct links between nuclear organization and circadian clocks.

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Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.134 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A66-A67

Author(s):

Audrey L Earnhardt ◽

David G Riley ◽

Noushin Ghaffari ◽

Penny K Riggs ◽

Charles R Long ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Target Genes ◽

Clock Genes ◽

Expression Profiles ◽

Primary Objective ◽

Clock Gene Expression ◽

Adrenal System ◽

Circadian Clock Genes

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P < 0.01) within each tissue with PER1 having greater expression in all tissues (P < 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P < 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P < 0.05), whereas CRY2 expression exceeded only CRY1 (P < 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P < 0.05). Overall, clock gene expression among tissues differed (P < 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P < 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P < 0.01), with PVN having greater expression than AP (P < 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P < 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P < 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P < 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P < 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P < 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P < 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.

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Different Effects of Phase Advance and Delay in Rotating Light-Dark Regimens on Clock and Natriuretic Peptide Gene Expression in the Rat Heart

Physiological Research ◽

10.33549/physiolres.932937 ◽

2014 ◽

pp. S573-S584 ◽

Cited By ~ 2

Author(s):

I. HERICHOVÁ ◽

J. AMBRUŠOVÁ ◽

Ľ. MOLČAN ◽

A. VESELÁ ◽

P. SVITOK ◽

...

Keyword(s):

Gene Expression ◽

Clock Genes ◽

Active Phase ◽

Circadian System ◽

Daily Rhythm ◽

Male Rats ◽

Phase Advance ◽

Peripheral Oscillators ◽

Peptide Gene ◽

Central Oscillator

Under physiological conditions the mammalian circadian system is synchronized to a cyclic environment. The central oscillator in the suprachiasmatic nuclei (SCN) responds predominantly to an external light (L) dark (D) cycle. Peripheral oscillators are more efficiently synchronized by metabolic cues. When the circadian system is exposed to opposing synchronizing cues, peripheral oscillators uncouple from the SCN. To consider influence of phase advances and delays in light regimens mimicking shift work, we analyzed the expression of clock genes (per2, bmal1) and natriuretic peptides (anp, bnp) in the heart of male rats. Experimental groups were exposed to a rotating LD regimen with either 8 h phase advance or delay for 11 weeks. Samples were taken for a 24 h cycle in 4 h intervals. Peripheral oscillators responded to rotating phase advance by decreasing rhythm robustness, while phase delay mostly influenced the phase angle between the acrophase of rhythmic gene expression and the external LD cycle. The expression of anp was arrhythmic in the heart of control rats and was not influenced by rotating LD regimens. The expression of bnp showed a daily rhythm with a nadir during the active phase. The daily rhythm in bnp expression diminished under rotating LD regimen conditions.

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