scholarly journals Linking circadian time to growth rate quantitatively via carbon metabolism

2017 ◽  
Author(s):  
Yin Hoon Chew ◽  
Daniel D. Seaton ◽  
Virginie Mengin ◽  
Anna Flis ◽  
Sam T. Mugford ◽  
...  

Summary paragraphPredicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate up time and length scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour, from sleep/wake cycles in mammals to flowering in plants1–3. Clock genes are rarely essential but appropriate alleles can confer a competitive advantage4,5 and have been repeatedly selected during crop domestication3,6. Here we quantitatively explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for growth of Arabidopsis thaliana7–9. The model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants. Altered night-time metabolism of stored starch accounted for most but not all of the decrease in whole-plant growth rate. Altered mobilisation of a secondary store of organic acids explained the remaining defect. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanlei Yue ◽  
Ze Jiang ◽  
Enoch Sapey ◽  
Tingting Wu ◽  
Shi Sun ◽  
...  

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.



2017 ◽  
Author(s):  
Trevor Martin ◽  
Hunter B. Fraser

AbstractAge is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.



Diabetologia ◽  
2004 ◽  
Vol 47 (8) ◽  
Author(s):  
T. Kudo ◽  
M. Akiyama ◽  
K. Kuriyama ◽  
M. Sudo ◽  
T. Moriya ◽  
...  


2020 ◽  
Author(s):  
◽  
Annique Claringbould

While humans share most of their genetic code with one another, small differences in the DNA can have an impact on an individual’s risk of disease. Common genetic variants exert individually small effects on the development of a disease, but their combined impact is substantial. Although recent research has identified thousands of variants that are associated to complex traits, our understanding of the molecular mechanisms that eventually lead to disease is limited. One way to dive into the molecular changes that result from genetic variation, is to look at changes in gene activity (‘gene expression’). Each cell contains the same genetic code, but genes are only expressed when and where they are required. Research has shown that many disease-associated genetic variants also affect gene expression. Such a change in the expression of a gene can lead to an altered level of the protein it encodes, which in turn can be the start of a dysregulation in the system that can eventually develop into a disease. This thesis describes how gene expression patterns can be used to prioritise and describe the function of trait-relevant genes. The first chapters evaluate methodological considerations for doing gene expression research. Another study covers the systematic linking of genetic variation to gene expression in blood and the last research chapter describes a method for gene prioritisation that leverages the idea that multiple genetic variants converge onto disease-causing genes. These insights can be used to better understand disease and to identify potential drug targets.



2017 ◽  
Author(s):  
Anna L. Tyler ◽  
Bo Ji ◽  
Daniel M. Gatti ◽  
Steven C. Munger ◽  
Gary A. Churchill ◽  
...  

ABSTRACTGenetic studies of multidimensional phenotypes can potentially link genetic variation, gene expression, and physiological data to create multi-scale models of complex traits. Multi-parent populations provide a resource for developing methods to understand these relationships. In this study, we simultaneously modeled body composition, serum biomarkers, and liver transcript abundances from 474 Diversity Outbred mice. This population contained both sexes and two dietary cohorts. Using weighted gene co-expression network analysis (WGCNA), we summarized transcript data into functional modules which we then used as summary phenotypes representing enriched biological processes. These module phenotypes were jointly analyzed with body composition and serum biomarkers in a combined analysis of pleiotropy and epistasis (CAPE), which inferred networks of epistatic interactions between quantitative trait loci that affect one or more traits. This network frequently mapped interactions between alleles of different ancestries, providing evidence of both genetic synergy and redundancy between haplotypes. Furthermore, a number of loci interacted with sex and diet to yield sex-specific genetic effects. We were also able to identify alleles that potentially protect individuals from the effects of a high-fat diet. Although the epistatic interactions explained small amounts of trait variance, the combination of directional interactions, allelic specificity, and high genomic resolution provided context to generate hypotheses for the roles of specific genes in complex traits. Our approach moves beyond the cataloging of single loci to infer genetic networks that map genetic etiology by simultaneously modeling all phenotypes.



PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1768 ◽  
Author(s):  
Jie Zhang ◽  
Jideng Ma ◽  
Keren Long ◽  
Long Jin ◽  
Yihui Liu ◽  
...  

A better understanding of the control of lipogenesis is of critical importance for both human and animal physiology. This requires a better knowledge of the changes of gene expression during the process of adipose tissue development. Thus, the objective of the current study was to determine the effects of development on subcutaneous adipose tissue gene expression in growing and adult pigs. Here, we present a comprehensive investigation of mRNA transcriptomes in porcine subcutaneous adipose tissue across four developmental stages using digital gene expression profiling. We identified 3,274 differential expressed genes associated with oxidative stress, immune processes, apoptosis, energy metabolism, insulin stimulus, cell cycle, angiogenesis and translation. A set of universally abundant genes (ATP8,COX2,COX3,ND1, ND2,SCDandTUBA1B) was found across all four developmental stages. This set of genes may play important roles in lipogenesis and development. We also identified development-related gene expression patterns that are linked to the different adipose phenotypes. We showed that genes enriched in significantly up-regulated profiles were associated with phosphorylation and angiogenesis. In contrast, genes enriched in significantly down-regulated profiles were related to cell cycle and cytoskeleton organization, suggesting an important role for these biological processes in adipose growth and development. These results provide a resource for studying adipose development and promote the pig as a model organism for researching the development of human obesity, as well as being used in the pig industry.



2021 ◽  
Vol 64 (2) ◽  
pp. 457-466
Author(s):  
Qi Han ◽  
Xiaoyun He ◽  
Ran Di ◽  
Mingxing Chu

Abstract. The circadian rhythm is a biological rhythm that is closely related to the rhythmic expression of a series of clock genes. Results from several studies have indicated that clock genes are associated with the estrous cycle in female animals. Until now, the relationship between estrus cycle transition and clock gene expression in reproductive-axis-related tissues has remained unknown in Small-tailed Han (STH) sheep. This study was conducted to analyze the expression patterns of six canonical clock genes (Clock, BMAL1, Per1, Per2, Cry1, and Cry2) in the follicle phase and luteal phase of STH sheep. We found that all six genes were expressed in the brain, cerebellum, hypothalamus, pituitary, ovary, uterus, and oviduct in follicle and luteal phases. The results indicated that Clock expression was significantly higher in the cerebellum, hypothalamus, and uterus of the luteal phase than that of the follicle phase, whereas BMAL1 expression was significantly higher in the hypothalamus of the luteal phase than that of the follicle phase. Per1 expression was significantly higher in the brain, cerebellum, hypothalamus, and pituitary of the luteal phase than that of the follicle phase, and Per2 expression was significantly higher in the hypothalamus, pituitary, and uterus of the luteal phase than that of the follicle phase. Cry1 expression was significantly higher in the brain, cerebellum, and hypothalamus of the luteal phase than that of the follicle phase, whereas Cry2 expression was significantly higher in the pituitary of the luteal phase than that of the follicle phase. The clock gene expression in all tissues was different between follicle and luteal phases, but all clock gene mRNA levels were found to exhibit higher expression among seven tissues in the luteal phase. Our results suggest that estrous cycles may be associated with clock gene expression in the STH sheep. This is the first study to systematically analyze the expression patterns of clock genes of different estrous cycle in ewes, which could form a basis for further studies to develop the relationship between clock genes and the estrous cycle.



2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2507-2507 ◽  
Author(s):  
G. A. Bjarnason ◽  
A. Seth ◽  
Z. Wang ◽  
N. Blanas ◽  
M. Straume ◽  
...  

2507 Background: DR in processes relevant to oncology, including cell cycle, apoptosis, and angiogenesis, have been demonstrated (Nat Rev Cancer 3:350, Cancer Res 63:7277). In rodents, 10–20% of the genome has a 24-hour (h) rhythm in RNA expression (Cell 109:307). A molecular clock consisting of transcription/translation feedback loops of clock-genes controls this rhythmicity (Nat Rev Neurosci 4:649). We studied, for the first time, daily whole genome RNA expression patterning in healthy human volunteers. Methods: RNA samples extracted from oral mucosa biopsies (bx) obtained every 4h over 24h (6 bx) from 5 males (M) and 5 females (F) were subjected to microarray analysis (Affymetrix HG_U133_Plus2 chip, 54,679 transcripts). COSOPT, designed for circadian microarray time series analysis (Methods Enzymol 383: 149) was used to detect genes with significant rhythms (pMMC-Beta = 0.1). Expression patterns were visualized in GeneSpring GX7.3 (Agilent) and validated by real-time PCR and ANOVA. Results: There were 801 and 810 rhythmic genes in M and F respectively, with most genes peaking at 4AM or 4PM in M but at 6AM or 11AM in F. Only 90 rhythmic genes (including core clock-genes and clock controlled genes) were common to M and F, with over 700 genes only rhythmic in M and not in F and vice versa. The profiles of clock- genes and clock-controlled genes were inverted relative to the nocturnal rodent data. There were 75 and 67 rhythmic transcription factor genes in M and F respectively, with 28 common to both M and F. There were 71 rhythmic human cancer genes (Nat Rev Cancer 4:177) with significant gender differences. This group includes rhythmic gene products involved in signaling pathways currently targeted for cancer Rx. Conclusions: We show for the first time a significant gender specific DR in gene expression involving multiple genes of interest in oncology. This may contribute to the documented gender differences in toxicity, response and survival (J Clin Onc 24: 3562, NEJM 353:133), and can inform future trials of optimal timing of antisense Rx and other targeted Rx. The inverted DR in rodents vs. humans has implications for translating rodent data to human Rx trials. No significant financial relationships to disclose.



2020 ◽  
Vol 48 (15) ◽  
pp. 8320-8331
Author(s):  
Xiangjun Ji ◽  
Peng Li ◽  
James C Fuscoe ◽  
Geng Chen ◽  
Wenzhong Xiao ◽  
...  

Abstract The rat is an important model organism in biomedical research for studying human disease mechanisms and treatments, but its annotated transcriptome is far from complete. We constructed a Rat Transcriptome Re-annotation named RTR using RNA-seq data from 320 samples in 11 different organs generated by the SEQC consortium. Totally, there are 52 807 genes and 114 152 transcripts in RTR. Transcribed regions and exons in RTR account for ∼42% and ∼6.5% of the genome, respectively. Of all 73 074 newly annotated transcripts in RTR, 34 213 were annotated as high confident coding transcripts and 24 728 as high confident long noncoding transcripts. Different tissues rather than different stages have a significant influence on the expression patterns of transcripts. We also found that 11 715 genes and 15 852 transcripts were expressed in all 11 tissues and that 849 house-keeping genes expressed different isoforms among tissues. This comprehensive transcriptome is freely available at http://www.unimd.org/rtr/. Our new rat transcriptome provides essential reference for genetics and gene expression studies in rat disease and toxicity models.



2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Cecilia A. Prator ◽  
Kar Mun Chooi ◽  
Dan Jones ◽  
Marcus W. Davy ◽  
Robin M. MacDiarmid ◽  
...  

Abstract Grapevine leafroll-associated virus 3 (GLRaV-3) is one of the most important viruses of grapevine but, despite this, there remain several gaps in our understanding of its biology. Because of its narrow host range - limited to Vitis species - and because the virus is restricted to the phloem, most GLRaV-3 research has concentrated on epidemiology and the development of detection assays. The recent discovery that GLRaV-3 can infect Nicotiana benthamiana, a plant model organism, makes new opportunities available for research in this field. We used RNA-seq to compare both V. vinifera and P1/HC-Pro N. benthamiana host responses to GLRaV-3 infection. Our analysis revealed that the majority of DEGs observed between the two hosts were unique although responses between the two hosts also showed several shared gene expression results. When comparing gene expression patterns that were shared between the two hosts, we observed the downregulation of genes associated with stress chaperones, and the induction of gene families involved in primary plant physiological processes. This is the first analysis of gene expression profiles beyond Vitis to mealybug-transmitted GLRaV-3 and demonstrates that N. benthamiana could serve as a useful tool for future studies of GLRaV-3-host interactions.



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