scholarly journals Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

2020 ◽  
Author(s):  
Jigme Dorji ◽  
Christy J. Vander Jagt ◽  
Josie B. Garner ◽  
Leah C. Marett ◽  
Brett Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Dairy Cattle ◽  
Differential Gene Expression ◽  
High Energy ◽  
Over Expression ◽  
Cellular Energy ◽  
Network Analyses ◽  
Cellular Energy Metabolism ◽  
Differential Gene

Abstract Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterised by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MPs) from both the nuclear ( Nu MP) and mitochondrial ( Mt MP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE Nu MP genes in varying proportions of over-expression and under-expression. On the other hand, DE of Mt MP genes was observed in <50% of tissues and notably Mt MP genes within a tissue was either all over-expressed or all under-expressed . A high proportion of Nu MP (up to 60%) and Mt MP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of Nu MP, 77% of Mt MP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all Mt MP genes in the direction of dominant Nu MP genes expression. The Nu MP and Mt MP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathways. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions This study demonstrated the biological interaction of MP genes from the mitochondrial and nuclear genomes and their over-expression in tissues with high energy demand. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.

scholarly journals Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jigme Dorji ◽  
Christy J. Vander Jagt ◽  
Josie B. Garner ◽  
Leah C. Marett ◽  
Brett A. Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Dairy Cattle ◽  
Differential Gene Expression ◽  
High Energy ◽  
Over Expression ◽  
Cellular Energy ◽  
Network Analyses ◽  
Cellular Energy Metabolism ◽  
Differential Gene

Abstract Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterized by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE NuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE of MtMP genes was observed in < 50% of tissues and notably MtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion of NuMP (up to 60%) and MtMP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of NuMP, 77% of MtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all MtMP genes in the direction of dominant NuMP genes expression. The NuMP and MtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathway. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions The results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.

scholarly journals Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

2020 ◽  
Author(s):  
Jigme Dorji ◽  
Christy J. Vander Jagt ◽  
Josie B. Garner ◽  
Leah C. Marett ◽  
Brett Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Dairy Cattle ◽  
Differential Gene Expression ◽  
High Energy ◽  
Over Expression ◽  
Cellular Energy ◽  
Network Analyses ◽  
Cellular Energy Metabolism ◽  
Differential Gene

Abstract Background: Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterised by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results: MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE NuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE of MtMP genes was observed in <50% of tissues and notably MtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion of NuMP (up to 60%) and MtMP ( up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of NuMP, 77% of MtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all MtMP genes in the direction of dominant NuMP genes expression. The NuMP and MtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathways. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions : The results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.

scholarly journals Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

2020 ◽  
Author(s):  
Jigme Dorji ◽  
Christy J. Vander Jagt ◽  
Josie B. Garner ◽  
Leah C. Marett ◽  
Brett Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Dairy Cattle ◽  
Differential Gene Expression ◽  
High Energy ◽  
Over Expression ◽  
Cellular Energy ◽  
Cellular Energy Metabolism ◽  
Mitochondrial Functions ◽  
Differential Gene

Abstract Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterized by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses.Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE NuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE of MtMP genes was observed in <50% of tissues and notably MtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion of NuMP (up to 60%) and MtMP ( up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of NuMP, 77% of MtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all MtMP genes in the direction of dominant NuMP genes expression. The NuMP and MtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathway. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets.Conclusions The results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.

scholarly journals The dynamics of mitochondrial-linked gene expression among tissues and life stages in two contrasting strains of laying hens

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262613
Author(s):  
Clara Dreyling ◽  
Martin Hasselmann
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Life Span ◽  
Laying Hens ◽  
Mitochondrial Gene ◽  
Model Organisms ◽  
Life Stages ◽  
Mitochondrial Gene Expression ◽  
Cellular Energy ◽  
Cellular Energy Metabolism

The cellular energy metabolism is one of the most conserved processes, as it is present in all living organisms. Mitochondria are providing the eukaryotic cell with energy and thus their genome and gene expression has been of broad interest for a long time. Mitochondrial gene expression changes under different conditions and is regulated by genes encoded in the nucleus of the cell. In this context, little is known about non-model organisms and we provide the first large-scaled gene expression analysis of mitochondrial-linked genes in laying hens. We analysed 28 mitochondrial and nuclear genes in 100 individuals in the context of five life-stages and strain differences among five tissues. Our study showed that mitochondrial gene expression increases during the productive life span, and reacts tissue and strain specific. In addition, the strains react different to potential increased oxidative stress, resulting from the increase in mitochondrial gene expression. The results suggest that the cellular energy metabolism as part of a complex regulatory system is strongly affected by the productive life span in laying hens and thus partly comparable to model organisms. This study provides a starting point for further analyses in this field on non-model organisms, especially in laying-hens.

Sculpturing New Muscle Phenotypes

Physiology ◽  
1988 ◽  
Vol 3 (3) ◽  
pp. 100-102 ◽  
Author(s):  
P Babij ◽  
FW Booth
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Energy Metabolism ◽  
Molecular Biology ◽  
Differential Gene Expression ◽  
Muscle Activity ◽  
Adaptive Responses ◽  
Signal Transducers ◽  
Enzymes Of Energy Metabolism ◽  
Differential Gene

Changes in the pattern of muscle activity are followed by new patterns of protein synthesis, both in the contractile elements and in the enzymes of energy metabolism. Although the signal transducers have not been identified, techniques of molecular biology have clearly shown that the adaptive responses are the regulated consequence of differential gene expression.

Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis

2005 ◽  
Vol 99 (3) ◽  
pp. 1120-1126 ◽  
Author(s):  
Leigh Ann Callahan ◽  
Gerald S. Supinski
Keyword(s):  
Gene Expression ◽  
Energy Metabolism ◽  
Electron Transport ◽  
Atp Synthase ◽  
Electron Transport Chain ◽  
Cellular Energy ◽  
Protein Levels ◽  
Cellular Energy Metabolism ◽  
Transport Chain ◽  
Genes Encoding

Cellular energy metabolism is altered in sepsis as a consequence of dysfunction of mitochondrial electron transport and glycolytic pathways. The purpose of the present study was to determine whether sepsis is associated with compensatory increases in gene expression of electron transport chain and glycolytic pathway proteins or, alternatively, whether gene expression decreases in sepsis, contributing to abnormalities in energy metabolism. Studies were performed using diaphragms from control and endotoxin-treated (8 mg·kg−1·day−1) rats; at 48 h after endotoxin administration, animals were killed. Microarrays and RNAse protection assays were used to assess the expression of several electron transport chain components (cytochrome- c oxidase subunits Cox 5A, Cox 5B, and Cox 6A, ATP synthase, and ATP synthase subunit 5B) and of the rate-limiting enzyme for glycolysis, phosphofructokinase (PFK). Western blotting was used to assess protein levels for these electron transport chain subunits and PFK. Activity assays were used to assess electron transport chain and phosphofructokinase function. We found that sepsis evoked 1) a downregulation of genes encoding all examined electron transport chain components (e.g., cytochrome- c oxidase 5A decreased 45 + 7%, P < 0.01) and PFK ( P < 0.001), 2) reductions in protein levels for these electron transport chain subunits and PFK ( P < 0.05 for each), and 3) decreases in mitochondrial state 3 respiration rates and phosphofructokinase enzyme activity ( P < 0.01 for each comparison). We speculate that these sepsis-induced reductions in the expression of genes encoding critical electron transport and glycolytic proteins contribute to the development and persistence of sepsis-induced abnormalities in cellular energy metabolism.

scholarly journals Weighted minimum feedback vertex sets and implementation in human cancer genes detection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ruiming Li ◽  
Chun-Yu Lin ◽  
Wei-Feng Guo ◽  
Tatsuya Akutsu
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Human Cancer ◽  
Gene Prediction ◽  
Optimal Solution ◽  
Interaction Network ◽  
Cancer Genes ◽  
Network Analyses ◽  
Gene Expression Analyses ◽  
Differential Gene

Abstract Background Recently, many computational methods have been proposed to predict cancer genes. One typical kind of method is to find the differentially expressed genes between tumour and normal samples. However, there are also some genes, for example, ‘dark’ genes, that play important roles at the network level but are difficult to find by traditional differential gene expression analysis. In addition, network controllability methods, such as the minimum feedback vertex set (MFVS) method, have been used frequently in cancer gene prediction. However, the weights of vertices (or genes) are ignored in the traditional MFVS methods, leading to difficulty in finding the optimal solution because of the existence of many possible MFVSs. Results Here, we introduce a novel method, called weighted MFVS (WMFVS), which integrates the gene differential expression value with MFVS to select the maximum-weighted MFVS from all possible MFVSs in a protein interaction network. Our experimental results show that WMFVS achieves better performance than using traditional bio-data or network-data analyses alone. Conclusion This method balances the advantage of differential gene expression analyses and network analyses, improves the low accuracy of differential gene expression analyses and decreases the instability of pure network analyses. Furthermore, WMFVS can be easily applied to various kinds of networks, providing a useful framework for data analysis and prediction.

scholarly journals RGL4 over Expression Correlates with Variation in Midostaurin Response in FLT3-ITD Mutant AML Samples

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1365-1365
Author(s):  
Mara Rosenberg ◽  
Cristina E. Tognon ◽  
Kevin M Watanabe-Smith ◽  
Uma Borate
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Rna Sequencing ◽  
Differential Gene Expression ◽  
Drug Sensitivity ◽  
Ex Vivo ◽  
Guanine Nucleotide ◽  
Kras Mutations ◽  
Over Expression ◽  
Differential Gene

Abstract Introduction: Acute Myeloid Leukemia (AML) is a heterogenous malignancy with the most common genomic alterations including mutations in NPM1, DNMT3A, and FLT3. Multiple FLT3-inhibitors have been developed and Midostaurin is the first to be FDA approved. However, while Midostaurin is now part of standard of care for FLT3 mutant AML patients undergoing induction chemotherapy, there is still a spectrum of clinical response. We hypothesized that additional biological factors could play a role in this variation of response. We previously observed that FLT3-ITD wildtype samples with KRAS mutations correlated with increased resistance to Midostaurin (1). Here, we utilized the Beat AML dataset containing over 900 AML patient samples processed through an ex vivo drug sensitivity screen to understand further whether genomic alterations could influence the range of Midostaurin response. Methods:We identified 180 (46 FLT3-ITD positive, 134 FLT3-ITD negative) de-novo primary AML peripheral blood or bone marrow samples from distinct patients within the Beat AML dataset. All samples included RNA-Sequencing profiling, mutational analyses, and ex-vivo Midostaurin drug screening data. Drug sensitivity was measured as area under a seven-point drug concentration curve (AUC). AUC was calculated as the area under the fitted probit curve (via direct integration) using all seven dose ranges as x-values and cell viability with limits from 0 to 100% as the y-value. RNA-Sequencing was normalized to counts per million (cpm) and the overall gene expression was chosen as the transcript of that gene with greatest average expression across the cohort. Differential gene expression was performed with the EdgeR package in R version 3.4.0. Results: As expected FLT3-ITD mutant samples, on average, are more sensitive to Midostaurin than FLT3-ITD wildtype sample. However, within the FLT3-ITD mutant cohort we observed a distribution of sensitivity responses (AUC mean of 55.4, IQR 35.5 - 75.3). Analysis of differential gene expression performed on the top 20% and bottom 20% of AUC values identified RGL4 over-expression across the entire resistant cohort (n = 9; Figure A). This was validated in an orthogonal data-set of 79 samples (21 mutant FLT3-ITD, 58 wildtype FLT3-ITD). To gain even more power within the validation set, we looked at all FLT3-ITD positive AUC values and observed a positive correlation between Midostaurin AUC and RGL4 expression (Spearman's rank correlation coefficient of 0.72, p < 0.05). Conclusions: In summary, we found that RGL4 over-expression correlated with resistance to Midostaurin in FLT3-ITD mutant samples in our ex vivo drug screen. RGL4 (ral guanine nucleotide dissociation stimulator like 4) encodes a protein similar to the guanine nucleotide exchange factor for Ral known as Ral GDS (guanine dissociation stimulator). It is highly expressed in the bone marrow and has the potential to activate the Ras-Raf-MEK-ERK pathway. As we had previously observed KRAS mutations correlating with resistance in FLT3-WT samples, this additional finding of RGL4 over expression supports the involvement of RAS pathway activation as a potential mechanism of resistance to Midostaurin. Additional in vitro studies are necessary to establish and further understand this mechanism as well as to test the efficacy of a Midostaurin / MEK inhibitor combination to treat resistant samples. 1. Watanabe-Smith, K., Rosenberg, M., Bucy, T., Tyner, J. W., & Borate, U.(2017). Factors Predicting Response and Resistance to Midostaurin in FLT3 Positive and FLT3 Negative AML in 483 Primary AML Patient Samples. Blood,130(Suppl 1), 296. Figure. Figure. Disclosures Borate: Novartis: Consultancy; Agios: Consultancy.

scholarly journals Sex-dependent differential transcript expression in the placenta of growth restricted infants

2021 ◽  
Author(s):  
Jessica O'Callaghan ◽  
Vicki Clifton ◽  
Peter Prentis ◽  
Adam Ewing ◽  
Zarqa Saif ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Rna Sequencing ◽  
Differential Gene Expression ◽  
Gestational Age ◽  
Transcript Expression ◽  
Network Analyses ◽  
Differential Gene

Objective: To characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants. Design: Case control study. Setting: Australian hospitals. Samples: Twelve human placental samples from pregnancies that were either SGA or appropriate for gestational age (AGA). Methods: RNA-sequencing of term placental tissue from both SGA and AGA infants. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations. Main outcome measures: Functions of differentially expressed genes in the placenta of SGA infants that differed by fetal sex. Results: Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. Sex-independent transcript expression for genes involved in protein synthesis, and sex-dependent transcript expression for genes involved in cell cycle processes in males and endoplasmic reticulum stress in females was validated (17 and 7 transcripts for females and males) in published placental RNA-sequencing datasets. Conclusions: Sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth. This study identified activation of shared and divergent molecular mechanisms (i.e., cell cycle and endoplasmic reticulum stress), in response to an adverse environmental stressor.

Sign in / Sign up

Export Citation Format

Share Document