Transcriptomic signatures of ageing vary in solitary and social forms of an orchid bee

AbstractEusocial insect queens are remarkable in their ability to maximise both fecundity and longevity, thus escaping the typical trade-off between these two traits. In species exhibiting complex eusocial behaviour, several mechanisms have been proposed to underlie the remoulding of the trade-off, such as reshaping of the juvenile hormone pathway, or caste-specific susceptibility to oxidative stress. However, it remains a challenge to disentangle the molecular mechanisms underlying the remoulding of the trade-off in eusocial insects from caste-specific physiological attributes that have subsequently arisen due to their different life histories. Socially plastic species such as the orchid bee Euglossa viridissima represent excellent models to address the role of sociality per se in longevity as they allow direct comparisons of solitary and social individuals within a common genetic background. We present data on gene expression and juvenile hormone levels from young and old bees, from both solitary and social nests. We found 940 genes to be differentially expressed with age in solitary females, versus only 14 genes in social dominant females, and seven genes in subordinate females. We performed a weighted gene co-expression network analysis to further highlight candidate genes related to ageing in this species. Primary “ageing gene” candidates were related to protein synthesis, gene expression, immunity and venom production. Remarkably, juvenile hormone titres did not vary with age or social status. These results represent an important step in understanding the proximate mechanisms underlying the remodeling of the fecundity/longevity trade-off that accompanies the evolutionary transition from solitary life to eusociality.Significance statementThe remarkably long lifespan of the queens of eusocial insects despite their high reproductive output suggests that they are not subject to the widespread trade-off between fecundity and longevity that governs solitary animal life histories, yet surprisingly little is known of the molecular mechanisms underpinning their longevity. Using a socially plastic bee in which some individuals of a population are social whilst others are solitary, we identified hundreds of candidate genes and related gene networks that are involved in the remoulding of the fecundity/longevity tradeoff. As well as identifying candidate ageing genes, our data suggest that even in incipient stages of sociality there is a marked reprogramming of ageing; long live the queen.

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Transcriptomic signatures of ageing vary in solitary and social forms of an orchid bee

Genome Biology and Evolution ◽

10.1093/gbe/evab075 ◽

2021 ◽

Author(s):

Alice Séguret ◽

Eckart Stolle ◽

Fernando A Fleites-Ayil ◽

José Javier G Quezada-Euán ◽

Klaus Hartfelder ◽

...

Keyword(s):

Oxidative Stress ◽

Juvenile Hormone ◽

Social Status ◽

Molecular Mechanisms ◽

Trade Off ◽

Eusocial Insects ◽

Proximate Mechanisms ◽

Orchid Bee ◽

Social Forms ◽

Age Related

Abstract Eusocial insect queens are remarkable in their ability to maximise both fecundity and longevity, thus escaping the typical trade-off between these two traits. Several mechanisms have been proposed to underlie the remoulding of the trade-off, such as reshaping of the juvenile hormone pathway, or caste-specific susceptibility to oxidative stress. However, it remains a challenge to disentangle the molecular mechanisms underlying the remoulding of the trade-off in eusocial insects from caste-specific physiological attributes that have subsequently arisen. The socially polymorphic orchid bee Euglossa viridissima represents an excellent model to address the role of sociality per se in longevity as it allows direct comparisons of solitary and social individuals within a common genetic background. We investigated gene expression and juvenile hormone levels in young and old bees from both solitary and social nests. We found 902 genes to be differentially expressed with age in solitary females, including genes involved in oxidative stress, versus only 100 genes in social dominant females, and 13 genes in subordinate females. A weighted gene co-expression network analysis further highlights pathways related to ageing in this species, including the TOR pathway. Eleven genes involved in translation, apoptosis and DNA repair show concurrent age-related expression changes in solitary but not in social females, representing potential differences based on social status. Juvenile hormone titres did not vary with age or social status. Our results represent an important step in understanding the proximate mechanisms underlying the remodelling of the fecundity/longevity trade-off that accompanies the evolutionary transition from solitary life to eusociality.

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The Western Diet Regulates Hippocampal Microvascular Gene Expression: An Integrated Genomic Analyses in Female Mice

Scientific Reports ◽

10.1038/s41598-019-55533-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Saivageethi Nuthikattu ◽

Dragan Milenkovic ◽

John Rutledge ◽

Amparo Villablanca

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Differential Expression ◽

Differential Gene Expression ◽

Gene Networks ◽

Molecular Mechanisms ◽

Western Diet ◽

Protein Coding ◽

Female Mice ◽

Differential Gene

AbstractHyperlipidemia is a risk factor for dementia, and chronic consumption of a Western Diet (WD) is associated with cognitive impairment. However, the molecular mechanisms underlying the development of microvascular disease in the memory centers of the brain are poorly understood. This pilot study investigated the nutrigenomic pathways by which the WD regulates gene expression in hippocampal brain microvessels of female mice. Five-week-old female low-density lipoprotein receptor deficient (LDL-R−/−) and C57BL/6J wild type (WT) mice were fed a chow or WD for 8 weeks. Metabolics for lipids, glucose and insulin were determined. Differential gene expression, gene networks and pathways, transcription factors, and non-protein coding RNAs were evaluated by genome-wide microarray and bioinformatics analysis of laser captured hippocampal microvessels. The WD resulted in differential expression of 2,412 genes. The majority of differential gene expression was attributable to differential regulation of cell signaling proteins and their transcription factors, approximately 7% was attributable to differential expression of miRNAs, and a lesser proportion was due to other non-protein coding RNAs, primarily long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs) not previously described to be modified by the WD in females. Our findings revealed that chronic consumption of the WD resulted in integrated multilevel molecular regulation of the hippocampal microvasculature of female mice and may provide one of the mechanisms underlying vascular dementia.

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Pleiotropic effects of juvenile hormone in ant queens and the escape from the reproduction–immunocompetence trade-off

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2409 ◽

2016 ◽

Vol 283 (1822) ◽

pp. 20152409 ◽

Cited By ~ 19

Author(s):

Tobias Pamminger ◽

David Treanor ◽

William O. H. Hughes

Keyword(s):

Gene Expression ◽

Juvenile Hormone ◽

Social Insect ◽

Reproductive Output ◽

Life History Evolution ◽

Lasius Niger ◽

Trade Off ◽

Regulatory Architecture ◽

Long Life ◽

Gonadotropic Hormones

The ubiquitous trade-off between survival and costly reproduction is one of the most fundamental constraints governing life-history evolution. In numerous animals, gonadotropic hormones antagonistically suppressing immunocompetence cause this trade-off. The queens of many social insects defy the reproduction–survival trade-off, achieving both an extraordinarily long life and high reproductive output, but how they achieve this is unknown. Here we show experimentally, by integrating quantification of gene expression, physiology and behaviour, that the long-lived queens of the ant Lasius niger have escaped the reproduction–immunocompetence trade-off by decoupling the effects of a key endocrine regulator of fertility and immunocompetence in solitary insects, juvenile hormone (JH). This modification of the regulatory architecture enables queens to sustain a high reproductive output without elevated JH titres and suppressed immunocompetence, providing an escape from the reproduction–immunocompetence trade-off that may contribute to the extraordinary lifespan of many social insect queens.

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Social modularity: conserved genes and regulatory elements underlie caste-antecedent behavioural states in an incipiently social bee

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.1815 ◽

2019 ◽

Vol 286 (1916) ◽

pp. 20191815 ◽

Cited By ~ 1

Author(s):

Wyatt A. Shell ◽

Sandra M. Rehan

Keyword(s):

Gene Expression ◽

Social Evolution ◽

Empirical Support ◽

Regulatory Elements ◽

Carpenter Bee ◽

Eusocial Insects ◽

Social Forms ◽

Evolutionary Origins ◽

Conserved Genes ◽

Insect Sociality

The evolutionary origins of advanced eusociality, one of the most complex forms of phenotypic plasticity in nature, have long been a focus within the field of sociobiology. Although eusocial insects are known to have evolved from solitary ancestors, sociogenomic research among incipiently social taxa has only recently provided empirical evidence supporting theories that modular regulation and deeply conserved genes may play important roles in both the evolutionary emergence and elaboration of insect sociality. There remains, however, a paucity of data to further test the biological reality of these and other evolutionary theories among taxa in the earliest stages of social evolution. Here, we present brain transcriptomic data from the incipiently social small carpenter bee, Ceratina calcarata , which captures patterns of cis -regulation and gene expression associated with female maturation, and underlying two well-defined behavioural states, foraging and guarding, concurrently demonstrated by mothers and daughters during early autumn. We find that an incipiently social nest environment may dramatically affect gene expression. We further reveal foraging and guarding behaviours to be putatively caste-antecedent states in C. calcarata , and offer strong empirical support for the operation of modular regulation, involving deeply conserved and differentially expressed genes in the expression of early social forms.

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Endurance training-induced changes in insulin sensitivity and gene expression

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00467.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1168-E1178 ◽

Cited By ~ 75

Author(s):

Margarita Teran-Garcia ◽

Tuomo Rankinen ◽

Robert A. Koza ◽

D. C. Rao ◽

Claude Bouchard

Keyword(s):

Gene Expression ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Candidate Genes ◽

Molecular Mechanisms ◽

Vastus Lateralis ◽

Intravenous Glucose Tolerance Test ◽

Vastus Lateralis Muscle ◽

Intravenous Glucose ◽

Before And After

The beneficial effects of regular physical activity on insulin sensitivity (SI) and glucose tolerance are well documented, with considerable heterogeneity in responsiveness to exercise training (ET). To find novel candidate genes for ET-induced improvement in SI, we used microarray technology. Total RNA was isolated from vastus lateralis muscle before and after 20 wk of exercise from individuals participating in the HERITAGE Family Study. SI index was derived from a frequently sampled intravenous glucose tolerance test using MINMOD Millennium software. Sixteen subjects were selected: eight showing no changes in SI (low responders, LSIR) and eight displaying marked improvement in SI (high responders, HSIR) with ET. The SI increase was about four times greater in HSIR compared with LSIR (+3.6 ± 0.5 vs. −1.2 ± 0.5 μU·ml−1·min−1, mean ± SE), whereas age, body mass index, percent body fat, and baseline SI were similar between the groups. Triplicate microarrays were performed, comparing pooled RNA with HSIR and LSIR individuals for differences in gene expression before and after ET using in situ-generated microarrays (18, 861 genes). Array data were validated by quantitative RT-PCR. Almost twice as many genes showed at least twofold differences between HSIR and LSIR after training compared with pretraining. We identified differentially expressed genes involved in energy metabolism and signaling, novel structural genes, and transcripts of unknown function. Genes of interest upregulated in HSIR include V-Ski oncogene, four-and-a-half LIM domain 1, and titin. Further study of these novel candidate genes should provide a better understanding of molecular mechanisms involved in the improvement in insulin sensitivity in response to regular exercise.

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The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms

10.1101/503318 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jian Cui ◽

Zhipeng Qu ◽

Yuka Harata-Lee ◽

Hanyuan Shen ◽

Thazin Nwe Aung ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cancer Cells ◽

Candidate Genes ◽

Cancer Cell ◽

Molecular Mechanisms ◽

Complex Mixtures ◽

Systematic Analysis ◽

Molecular Changes ◽

Compound Kushen Injection

AbstractBackgroundBecause Traditional Chinese Medicine (TCM) preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study. Compound Kushen Injection (CKI) is a complex mixture cancer treatment used in Chinese hospitals for over twenty years.PurposeTo demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways.Study DesignWe used a cancer cell culture model to measure the effect of CKI on cell cycle phases, apoptosis and correlate those phenotypes with CKI induced changes in gene expression.MethodsWe treated cancer cells with CKI in order to generate and analyse high-throughput transcriptome data from two cancer cell lines. We integrated these differential gene expression results with previously reported results.ResultsCKI induced cell-cycle arrest and apoptosis and altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes.ConclusionsBy identifying promising candidate pathways and genes associated with CKI based on our transcriptome-based analysis, we have shown this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.

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Schizophrenia hiPSC neurons display expression changes that are enriched for disease risk variants and a blunted activity-dependent response

10.1101/062885 ◽

2016 ◽

Author(s):

Panos Roussos ◽

Boris Guennewig ◽

Dominik C. Kaczorowski ◽

Guy Barry ◽

Kristen J. Brennand

Keyword(s):

Gene Expression ◽

Candidate Genes ◽

Expression Analysis ◽

Gene Networks ◽

Disease Risk ◽

Fragile X ◽

Differential Expression Analysis ◽

Therapeutic Interventions ◽

Risk Variants ◽

Activity Dependent

ABSTRACTIMPORTANCESchizophrenia (SCZ) is a common illness with complex genetic architecture where both common genetic variation and rare mutations have been implicated. SCZ candidate genes participate in common molecular pathways that are regulated by activity-dependent changes in neurons, including the signaling network that modulates synaptic strength and the network of genes that are targets of fragile X mental retardation protein. One important next step is to further our understanding on the role of activity-dependent changes of genes expression in the etiopathogenesis of SCZ.OBJECTIVETo examine whether neuronal activity-dependent changes of gene expression is dysregulated in SCZ.DESIGN, SETTING, AND PARTICIPANTSNeurons differentiated from human induced pluripotent stem cells (hiPSCs) derived from 4 cases with SCZ and 4 unaffected controls were depolarized using potassium chloride. RNA was extracted followed by genome-wide profiling of the transcriptome.MAIN OUTCOMES AND MEASURESWe performed differential expression analysis and gene co-expression analysis to identify activity-dependent or disease-specific changes of the transcriptome. Further, we used gene set analyses to identify co-expressed modules that are enriched for SCZ risk genes.RESULTSWe identified 1,669 genes that are significantly different in SCZ-associated vs. control hiPSC-derived neurons and 1,199 genes that are altered in these cells in response to depolarization. We show that the effect of activity-dependent changes of gene expression in SCZ-associated neurons is attenuated compared to controls. Furthermore, these differentially expressed genes are co-expressed in modules that are highly enriched for genes affected by genetic risk variants in SCZ and other neurodevelopmental disorders.CONCLUSIONS AND RELEVANCEOur results show that SCZ candidate genes converge to gene networks that are associated with a blunted effect of activity-dependent changes of gene expression in SCZ-associated neurons. Overall, these findings show that hiPSC neurons demonstrate activity-dependent transcriptional changes that can be utilized to examine underlying mechanisms and therapeutic interventions related to SCZ.

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Identification of prognostic risk factors for pancreatic cancer using bioinformatics analysis

PeerJ ◽

10.7717/peerj.9301 ◽

2020 ◽

Vol 8 ◽

pp. e9301

Author(s):

Dandan Jin ◽

Yujie Jiao ◽

Jie Ji ◽

Wei Jiang ◽

Wenkai Ni ◽

...

Keyword(s):

Gene Expression ◽

Pancreatic Cancer ◽

Gene Networks ◽

Molecular Mechanisms ◽

Functional Module ◽

Disease Free Survival ◽

Ductal Adenocarcinoma ◽

Literature Mining ◽

Ppi Network ◽

Hub Genes

Background Pancreatic cancer is one of the most common malignant cancers worldwide. Currently, the pathogenesis of pancreatic cancer remains unclear; thus, it is necessary to explore its precise molecular mechanisms. Methods To identify candidate genes involved in the tumorigenesis and proliferation of pancreatic cancer, the microarray datasets GSE32676, GSE15471 and GSE71989 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between Pancreatic ductal adenocarcinoma (PDAC) and nonmalignant samples were screened by GEO2R. The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool was used to obtain a synthetic set of functional annotation information for the DEGs. A PPI network of the DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and a combination of more than 0.4 was considered statistically significant for the PPI. Subsequently, we visualized the PPI network using Cytoscape. Functional module analysis was then performed using Molecular Complex Detection (MCODE). Genes with a degree ≥10 were chosen as hub genes, and pathways of the hub genes were visualized using ClueGO and CluePedia. Additionally, GenCLiP 2.0 was used to explore interactions of hub genes. The Literature Mining Gene Networks module was applied to explore the cocitation of hub genes. The Cytoscape plugin iRegulon was employed to analyze transcription factors regulating the hub genes. Furthermore, the expression levels of the 13 hub genes in pancreatic cancer tissues and normal samples were validated using the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Moreover, overall survival and disease-free survival analyses according to the expression of hub genes were performed using Kaplan-Meier curve analysis in the cBioPortal online platform. The relationship between expression level and tumor grade was analyzed using the online database Oncomine. Lastly, the eight snap-frozen tumorous and adjacent noncancerous adjacent tissues of pancreatic cancer patients used to detect the CDK1 and CEP55 protein levels by western blot. Conclusions Altogether, the DEGs and hub genes identified in this work can help uncover the molecular mechanisms underlying the tumorigenesis of pancreatic cancer and provide potential targets for the diagnosis and treatment of this disease.

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Alternative migratory tactics in brown trout (Salmo trutta) are underpinned by divergent regulation of metabolic but not neurological genes

10.22541/au.161107458.80549176/v1 ◽

2021 ◽

Author(s):

Robert Wynne ◽

Louise Archer ◽

Stephen Hutton ◽

Luke Harman ◽

Patrick Gargan ◽

...

Keyword(s):

Gene Expression ◽

Brown Trout ◽

Life Histories ◽

Salmo Trutta ◽

Molecular Mechanisms ◽

Molecular Genetic ◽

Specific Gene ◽

Metabolic Processes ◽

Tissue Specific ◽

The Brain

The occurrence of alternative morphs within populations is common but the underlying molecular mechanisms remain poorly understood. Many animals, for example, exhibit facultative migration, where two or more alternative migratory tactics (AMTs) coexist within populations. In certain salmonid species, some individuals remain in natal rivers all their lives, whilst others (in particular, females) migrate to sea for a period of marine growth. Here we performed transcriptional profiling (“RNA-seq”) of the brain and liver of male and female brown trout to understand the genes and processes that differentiate migratory and residency morphs (AMT-associated genes) and how they may differ in expression between the sexes. We found tissue-specific differences with greater number of genes expressed differentially in the liver (n = 867 genes) compared to the brain (n = 10) between the morphs. Genes with increased expression in resident livers were enriched for Gene Ontology terms associated with metabolic processes, highlighting key molecular-genetic pathways underlying the energetic requirements associated with divergent migratory tactics. In contrast, smolt-biased genes were enriched for biological processes such as response to cytokines, suggestive of possible immune function differences between smolts and residents. Finally, we identified evidence of sex-biased gene expression for AMT-associated genes in the liver (n = 18) but not the brain. Collectively, our results provide insights into tissue-specific gene expression underlying the production of alternative life-histories within and between the sexes, and point towards a key role for metabolic processes in the liver in mediating divergent physiological trajectories of migrants versus residents.

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