scholarly journals The urban-adapted underground mosquito, Culex pipiens form molestus, maintains exogenously influenceable circadian rhythms

2021 ◽  
Author(s):  
Natalie R. Epstein ◽  
Kevin Saez ◽  
Asya Polat ◽  
Steven R. Davis ◽  
Matthew L. Aardema
Keyword(s):  
Circadian Rhythms ◽  
Culex Pipiens ◽  
Clock Genes ◽  
Splice Variants ◽  
Life Stage ◽  
Diapause Induction ◽  
Nucleotide Polymorphisms ◽  
Molecular Changes ◽  
Regulatory Effects ◽  
Circadian Behavior

Genes known to affect circadian rhythms (i.e. ‘clock genes’) also influence the photoperiodic induction of overwintering reproductive diapause in the Northern house mosquito, Culex pipiens f. pipiens. This suggests that molecular changes in one or more clock genes could contribute to the inability to diapause in a second form of this mosquito, Cx. pipiens f. molestus. Temperate populations of Cx. pipiens f. molestus inhabit underground locations generally devoid of predictable photoperiods. For this reason, there could be limited fitness consequences if the hypothesized molecular changes to its clock genes also eliminated this mosquito's ability to regulate circadian rhythms in response to photoperiod variation. Here we demonstrate that in contrast to this prediction, underground derived Cx. pipiens f. molestus retain exogenously-influenceable circadian rhythms. Nonetheless, our genetic analyses indicate that the gene Helicase domino (dom) has a nine-nucleotide, in-frame deletion specific to Cx. pipiens f. molestus. Previous work has shown that splice variants in this gene differentially influence circadian behavior in Drosophila melanogaster. We also find derived, non-synonymous single nucleotide polymorphisms (SNPs) in eight genes that may also affect circadian rhythms and/or diapause induction in Cx. pipiens f. molestus. Finally, four putative circadian genes were found to have no quantifiable expression during any examined life-stage, suggesting potential regulatory effects. Collectively, our findings indicate that the distinct, but molecularly interconnected life-history traits of diapause induction and circadian rhythms are decoupled in Cx. pipiens f. molestus and suggest this taxon may be a valuable tool for exploring exogenously influenced phenotypes in mosquitoes more broadly.

scholarly journals The urban-adapted underground mosquito, Culex molestus, maintains exogenously influenced circadian rhythms despite an absence of photoperiodically induced dormancy

2020 ◽  
Author(s):  
Natalie R. Epstein ◽  
Kevin Saez ◽  
Asya Polat ◽  
Steven R. Davis ◽  
Matthew L. Aardema
Keyword(s):  
Circadian Rhythms ◽  
Clock Genes ◽  
Splice Variants ◽  
Life Stage ◽  
Experimental Studies ◽  
Purifying Selection ◽  
Diapause Induction ◽  
Nucleotide Polymorphisms ◽  
Genetic Changes ◽  
Dormant State

ABSTRACTIn temperate climates, the mosquito Culex molestus lives almost exclusively in urban underground locations such as flooded basements, sewer systems and subway tunnels. Unlike most other mosquito taxa found at higher latitudes, Cx. molestus remains active and continues to breed throughout the winter. This is attributable to year-round above freezing temperatures in its preferred underground habitats combined with an inability to enter a state of arrested development (‘diapause’) in response to shortening photoperiods in autumn. Prior studies have shown that the genes associated with circadian rhythms (i.e. ‘clock genes’) also influence the photoperiodic induction of diapause in the closely related mosquito, Cx. pipiens. These results suggest that molecular changes in one or more clock genes could contribute to the absence of photoperiodically induced diapause in Cx. molestus. As Cx. molestus predominantly inhabits underground locations generally devoid of a predictable photoperiod, such mutations may not be removed by purifying selection as they would have minimal fitness consequences. To examine the possibility that Cx. molestus- specific genetic changes in one or more clock genes correlate with its inability to enter a photoperiodically induced dormant state, we first used genomic data to search for inactivating mutations or other structural variants in genes known to influence circadian rhythms in Diptera (‘flies’). We further investigated non-synonymous, derived genetic divergence in this same class of genes. Next, we generated transcriptome data from multiple life-stages of Cx. molestus to survey binary expression of annotated clock genes throughout this mosquito’s lifecycle. Finally, we carried out experimental studies to assess the extent to which Cx. molestus retains exogenously influenced circadian rhythms, and whether it harbors any tendencies towards dormancy when exposed to a shortened photoperiod. Our results indicate that the gene Helicase domino (dom) has a nine-nucleotide, in-frame deletion specific to Cx. molestus. Previous work has shown that splice variants in this gene influence circadian behavior in Drosophila melanogaster. We also find derived, non-synonymous single nucleotide polymorphisms (SNPs) in eight genes that may also affect circadian rhythms and/or diapause induction in Cx. molestus. Four other circadian genes were found to have no quantifiable expression during any examined life stage, suggesting potential regulatory variation. Our experimental results confirm that Cx. molestus retains exogenously-influenced circadian rhythms but is not induced to enter a dormant state by a shortened photoperiod. Collectively, these findings show that the distinct, but potentially molecularly interconnected life-history traits of diapause induction and circadian rhythms are decoupled in Cx. molestus and suggest that this taxon may be a valuable tool for exploring exogenously influenced phenotypes in mosquitoes more broadly.

scholarly journals Associations of chronotype with clock genes polymorphisms

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Mirkka Maukonen ◽  
Aki Havulinna ◽  
Timo Partonen ◽  
Noora Kanerva ◽  
Satu Männistö
Keyword(s):  
Circadian Rhythms ◽  
Dietary Habits ◽  
Clock Genes ◽  
Genetic Model ◽  
Statistical Significance ◽  
Minor Allele ◽  
Lipid Absorption ◽  
Nucleotide Polymorphisms ◽  
Metabolic Disturbances ◽  
Cross Sectional

AbstractIntroductionIndividuals with a later timing of circadian rhythms (evening types) tend to have unhealthier behaviors compared to those with an earlier timing (morning types). Previous studies have shown that evening types have unhealthier diets and later eating times than morning types. Furthermore, evening types bear higher odds for type 2 diabetes and weight gain (women). Circadian rhythms are controlled by clock genes which have an important role in regulating energy homeostasis. Thus far, a number of single nucleotide polymorphisms (SNP) of clock genes have been associated with metabolic disturbances, obesity and dietary habits (e.g., breakfast skipping and macronutrient intakes). Our aim was to examine chronotype associations with SNPs of the 20 known key clock genes which could help to clarify the underlying mechanisms behind chronotype phenotype.MethodsOur data included 8558 participants (aged 25–74 years, 52% of women) from the cross-sectional population-based National FINRISK 2007 and 2012 surveys. Chronotype was assessed with a shortened six-item version of Horne and Östberg's Morningness-Eveningness Questionnaire (sMEQ) accounting for 83% of the total variance of the original questionnaire. For comparison we used a single self-evaluation question on chronotype from the questionnaire. Genotyping was done using Illumina arrays (HumanCoreExome, Omniexpress and 610K). Linear and logistic regression was used for statistical analysis with the additive genetic model. The analyses were adjusted for age, sex, batch effects and five principal components to account for population structure. The false discovery rate method by the Benjamini-Yekutieli procedure was applied to correct for multiple comparisons.ResultsWe found 27 SNPs in two clock genes that were significantly (P < 0.05) associated with chronotype when assessed with the single question. Minor allele carriers of the NR1D2 (Rev-erbβ) polymorphisms (rs4131403A, rs4858095T, rs6794922G, rs4619734A, rs4589882A, rs4321479C, rs6779476A, rs6790557A, rs13095392A, rs4858098G, rs4858567C, rs11717862G, rs7431301A, rs5023610G, rs5847265C, rs5847266G, rs6550823A, rs9882735C, rs7371944A, rs55792500G) were associated with evening type, whereas minor allele carriers of the NFIL3 polymorphisms (rs2482704T, rs2989836T, rs2482356C, rs2440589T, rs9409419G, rs2482702G, rs2482357A) were more likely morning types. Findings were similar when chronotype was assessed with sMEQ but did not reach statistical significance.DiscussionOur findings indicated novel genetic associations of chronotype with two clock genes that have previously been associated with carbohydrate and lipid metabolism (NR1D2), and with lipid absorption and export in intestinal epithelial cells and hepatic gluconeogenesis (NFIL3). These results expand our knowledge of the genetic basis of chronotype and warrant further studies to replicate these findings.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals Shared Components of the FRQ-Less Oscillator and TOR Pathway Maintain Rhythmicity in Neurospora

2021 ◽  
pp. 074873042199994
Author(s):  
Rosa Eskandari ◽  
Lalanthi Ratnayake ◽  
Patricia L. Lakin-Thomas
Keyword(s):  
Circadian Rhythms ◽  
Clock Genes ◽  
Nutrient Sensing ◽  
Mass Spectrometry Analysis ◽  
Growth Responses ◽  
Tor Pathway ◽  
Spectrometry Analysis ◽  
Binding Partner ◽  
Binding Partners ◽  
Free Running

Molecular models for the endogenous oscillators that drive circadian rhythms in eukaryotes center on rhythmic transcription/translation of a small number of “clock genes.” Although substantial evidence supports the concept that negative and positive transcription/translation feedback loops (TTFLs) are responsible for regulating the expression of these clock genes, certain rhythms in the filamentous fungus Neurospora crassa continue even when clock genes ( frq, wc-1, and wc-2) are not rhythmically expressed. Identification of the rhythmic processes operating outside of the TTFL has been a major unresolved area in circadian biology. Our lab previously identified a mutation ( vta) that abolishes FRQ-less rhythmicity of the conidiation rhythm and also affects rhythmicity when FRQ is functional. Further studies identified the vta gene product as a component of the TOR (Target of Rapamycin) nutrient-sensing pathway that is conserved in eukaryotes. We now report the discovery of TOR pathway components including GTR2 (homologous to the yeast protein Gtr2, and RAG C/D in mammals) as binding partners of VTA through co-immunoprecipitation (IP) and mass spectrometry analysis using a VTA-FLAG strain. Reciprocal IP with GTR2-FLAG found VTA as a binding partner. A Δ gtr2 strain was deficient in growth responses to amino acids. Free-running conidiation rhythms in a FRQ-less strain were abolished in Δ gtr2. Entrainment of a FRQ-less strain to cycles of heat pulses demonstrated that Δ gtr2 is defective in entrainment. In all of these assays, Δ gtr2 is similar to Δ vta. In addition, expression of GTR2 protein was found to be rhythmic across two circadian cycles, and functional VTA was required for GTR2 rhythmicity. FRQ protein exhibited the expected rhythm in the presence of GTR2 but the rhythmic level of FRQ dampened in the absence of GTR2. These results establish association of VTA with GTR2, and their role in maintaining functional circadian rhythms through the TOR pathway.

scholarly journals Sex Differences in Circadian Clock Genes and Myocardial Infarction Susceptibility

2021 ◽  
Vol 8 (5) ◽  
pp. 53
Author(s):  
Ivana Škrlec ◽  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Robert Steiner
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Circadian Rhythm ◽  
Single Nucleotide Polymorphisms ◽  
Clock Genes ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Biological Sex ◽  
Significant Difference

The growing body of evidence shows a significant difference in the circadian rhythm of cardiovascular disease based on biological sex. The incidence of cardiovascular disease varies between women and men. Additionally, biological sex is vital for the timely application of therapy—chronotherapy, which benefits both sexes. This study aimed to examine the potential difference of single nucleotide polymorphisms (SNPs) of the circadian rhythm genes ARNTL, CLOCK, CRY2 and PER2 in women and men with myocardial infarction. A cross-sectional study was conducted, including 200 patients with myocardial infarction. Altogether, ten single nucleotide polymorphisms in the ARNTL, CLOCK, CRY2 and PER2 genes were analyzed. The Chi-square test yielded statistically significant differences in CLOCK gene rs11932595 polymorphism in a recessive genotype model between women and men with a p-value of 0.03 and an odds ratio 2.66, and a corresponding 95% confidence interval of 1.07 to 6.66. Other analyzed polymorphisms of the circadian rhythm genes ARNTL, CRY2, and PER2 did not significantly differ between the sexes. According to the study’s current results, the CLOCK gene’s genetic variability might affect myocardial infarction concerning biological sex.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Detecting Genetic Associations betweenATG5and Lupus Nephritis bytrans-eQTL

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yue-miao Zhang ◽  
Fa-juan Cheng ◽  
Xu-jie Zhou ◽  
Yuan-yuan Qi ◽  
Ping Hou ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Information ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Genome Wide ◽  
Custom Made ◽  
Regulatory Effects

Objectives. Numerous loci were identified to perturb gene expression intrans. As elevatedATG5expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated withATG5expression in a Chinese population with lupus nephritis (LN).Methods. The online expression quantitative trait loci database was searched fortrans-expression single nucleotide polymorphisms (trans-eSNPs) ofATG5. Taggingtrans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed.Results. Fourtrans-eSNPs were observed to be associated with susceptibility to LN (P< 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven othertrans-eSNPs showed marginal significant associations (0.05 <P< 0.1). Correlations between thetrans-eSNPs andATG5expression and different expression levels ofATG5in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes oftrans-eSNPs and severity or outcome of the patients.Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.

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