scholarly journals Paralogs in the PKA regulon traveled different evolutionary routes to divergent expression in budding yeast

2019 ◽  
Author(s):  
Benjamin Murray Heineike ◽  
Hana El-Samad
Keyword(s):  
Differential Expression ◽  
Functional Divergence ◽  
Transcriptional Response ◽  
Differentially Expressed ◽  
Environmental Stress Response ◽  
Generating Functional ◽  
Promoter Sequences ◽  
Gene Pairs ◽  
Basal Expression ◽  
Paralog Gene

AbstractFunctional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ∼100MYA. Many WGH paralogs (or ohnologs) are known to have differential expression during the yeast Environmental Stress Response (ESR), of which Protein Kinase A (PKA) is a major regulator. While investigating the transcriptional response to PKA inhibition in S. cerevisiae, we discovered that approximately 1/6th (91) of all ohnolog pairs were differentially expressed with a striking pattern. One member of each pair tended to have low basal expression that increased upon PKA inhibition, while the other tended to have high but unchanging expression. Examination of PKA inhibition data in the pre-WGH species K. lactis and PKA-related stresses in other budding yeasts indicated that unchanging expression in response to PKA inhibition is likely to be the ancestral phenotype prior to duplication. Analysis of promoter sequences of orthologs of gene pairs that are differentially expressed in S. cerevisiae further revealed that the emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence, which can persist even when functional differences are erased by gene conversion.

scholarly journals Paralogs in the PKA Regulon Traveled Different Evolutionary Routes to Divergent Expression in Budding Yeast

2021 ◽  
Vol 2 ◽  
Author(s):  
Benjamin M. Heineike ◽  
Hana El-Samad
Keyword(s):  
Yeast Species ◽  
Budding Yeast ◽  
Kluyveromyces Lactis ◽  
Functional Divergence ◽  
Promoter Sequence ◽  
Duplicate Genes ◽  
Generating Functional ◽  
Basal Expression ◽  
Genes Expression ◽  
Paralog Gene

Functional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ~100MYA. In this work, we report that ~1/6th (110) of these WGH paralogs pairs (or ohnologs) are differentially expressed with a striking pattern upon Protein Kinase A (PKA) inhibition. One member of each pair in this group has low basal expression that increases upon PKA inhibition, while the other has moderate and unchanging expression. For these genes, expression of orthologs upon PKA inhibition in the non-WGH species Kluyveromyces lactis and for PKA-related stresses in other budding yeasts shows unchanging expression, suggesting that lack of responsiveness to PKA was likely the typical ancestral phenotype prior to duplication. Promoter sequence analysis across related budding yeast species further revealed that the subsequent emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence.

scholarly journals Effect of Anaerobiosis and Nitrate on Gene Expression in Pseudomonas aeruginosa

2005 ◽  
Vol 73 (6) ◽  
pp. 3764-3772 ◽  
Author(s):  
M. J. Filiatrault ◽  
V. E. Wagner ◽  
D. Bushnell ◽  
C. G. Haidaris ◽  
B. H. Iglewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Differential Expression ◽  
Dna Microarrays ◽  
Transcriptional Response ◽  
Anaerobic Growth ◽  
Differentially Expressed

ABSTRACT DNA microarrays were used to examine the transcriptional response of Pseudomonas aeruginosa to anaerobiosis and nitrate. In response to anaerobic growth, 691 transcripts were differentially expressed. Comparisons of P. aeruginosa grown aerobically in the presence or the absence of nitrate showed differential expression of greater than 900 transcripts.

scholarly journals Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal

2012 ◽  
Vol 44 (1) ◽  
pp. 25-34 ◽  
Author(s):  
E. H. Wall ◽  
J. P. Bond ◽  
T. B. McFadden
Keyword(s):  
Differential Expression ◽  
Milk Yield ◽  
Bovine Genome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Transcriptional Response ◽  
Differentially Expressed ◽  
Yield Response ◽  
Mammary Tissue ◽  
Early Lactation

Milking dairy cows four times daily (4×) instead of twice daily (2×) during early lactation stimulates an increase in milk yield that partly persists through late lactation; however, the mechanisms behind this response are unknown. We hypothesized that the acute mammary response to regular milkings would be transient and would involve different genes from those that may be specifically regulated in response to 4×. Nine multiparous cows were assigned at parturition to unilateral frequent milking (UFM; 2× of the left udder half, 4× of the right udder half). Mammary biopsies were obtained from both rear quarters at 5 days in milk (DIM), immediately after 4× glands had been milked ( experiment 1, n = 4 cows), or 2.5 h after both udder halves had last been milked ( experiment 2, n = 5 cows). Affymetrix GeneChip Bovine Genome Arrays were used to measure gene expression. We found 855 genes were differentially expressed in mammary tissue between 2× vs. 4× glands of cows in experiment 1 (false discovery rate ≤ 0.05), whereas none were differentially expressed in experiment 2 using the same criterion. We conclude that there is an acute transcriptional response to milk removal, but 4× milking did not elicit differential expression of unique genes. Therefore, there does not appear to be a sustained transcriptional response to 4× milking on day 5 of lactation. Using a differential expression plot of data from both experiments, as well as qRT-PCR, we identified at least two genes (chitinase 3-like-1 and low-density lipoprotein-related protein-2 that may be responsive to both milk removal and to 4× milking. Therefore, the milk yield response to 4× milking may be mediated by genes that are acutely regulated by removal of milk from the mammary gland.

scholarly journals Differential Gene Expression between Fungal Mating Types Is Associated with Sequence Degeneration

2020 ◽  
Vol 12 (4) ◽  
pp. 243-258 ◽  
Author(s):  
Wen-Juan Ma ◽  
Fantin Carpentier ◽  
Tatiana Giraud ◽  
Michael E Hood
Keyword(s):  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Mating Type ◽  
Sex Chromosomes ◽  
Sex Chromosome ◽  
Gc Content ◽  
Differentially Expressed ◽  
Mating Types ◽  
Sexual Antagonism ◽  
Recombination Suppression

Abstract Degenerative mutations in non-recombining regions, such as in sex chromosomes, may lead to differential expression between alleles if mutations occur stochastically in one or the other allele. Reduced allelic expression due to degeneration has indeed been suggested to occur in various sex-chromosome systems. However, whether an association occurs between specific signatures of degeneration and differential expression between alleles has not been extensively tested, and sexual antagonism can also cause differential expression on sex chromosomes. The anther-smut fungus Microbotryum lychnidis-dioicae is ideal for testing associations between specific degenerative signatures and differential expression because 1) there are multiple evolutionary strata on the mating-type chromosomes, reflecting successive recombination suppression linked to mating-type loci; 2) separate haploid cultures of opposite mating types help identify differential expression between alleles; and 3) there is no sexual antagonism as a confounding factor accounting for differential expression. We found that differentially expressed genes were enriched in the four oldest evolutionary strata compared with other genomic compartments, and that, within compartments, several signatures of sequence degeneration were greater for differentially expressed than non-differentially expressed genes. Two particular degenerative signatures were significantly associated with lower expression levels within differentially expressed allele pairs: upstream insertion of transposable elements and mutations truncating the protein length. Other degenerative mutations associated with differential expression included nonsynonymous substitutions and altered intron or GC content. The association between differential expression and allele degeneration is relevant for a broad range of taxa where mating compatibility or sex is determined by genes located in large regions where recombination is suppressed.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals Physiological and transcriptional response to drought stress among bioenergy grass Miscanthus species

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jose J. De Vega ◽  
Abel Teshome ◽  
Manfred Klaas ◽  
Jim Grant ◽  
John Finnan ◽  
...  
Keyword(s):  
Drought Stress ◽  
Water Supply ◽  
Biomass Yield ◽  
Transcriptional Response ◽  
Biomass Productivity ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Drought Conditions ◽  
Multiple Copies ◽  
Response To Water

Abstract Background Miscanthus is a commercial lignocellulosic biomass crop owing to its high biomass productivity, resilience and photosynthetic capacity at low temperature. These qualities make Miscanthus a particularly good candidate for temperate marginal land, where yields can be limited by insufficient or excessive water supply. Differences in response to water stress have been observed among Miscanthus species, which correlated to origin. In this study, we compared the physiological and molecular responses among Miscanthus species under excessive (flooded) and insufficient (drought) water supply in glasshouse conditions. Results A significant biomass loss was observed under drought conditions in all genotypes. M. x giganteus showed a lower reduction in biomass yield under drought conditions compared to the control than the other species. Under flooded conditions, biomass yield was as good as or better than control conditions in all species. 4389 of the 67,789 genes (6.4%) in the reference genome were differentially expressed during drought among four Miscanthus genotypes from different species. We observed the same biological processes were regulated across Miscanthus species during drought stress despite the DEGs being not similar. Upregulated differentially expressed genes were significantly involved in sucrose and starch metabolism, redox, and water and glycerol homeostasis and channel activity. Multiple copies of the starch metabolic enzymes BAM and waxy GBSS-I were strongly up-regulated in drought stress in all Miscanthus genotypes, and 12 aquaporins (PIP1, PIP2 and NIP2) were also up-regulated in drought stress across genotypes. Conclusions Different phenotypic responses were observed during drought stress among Miscanthus genotypes from different species, supporting differences in genetic adaption. The low number of DEGs and higher biomass yield in flooded conditions supported Miscanthus use in flooded land. The molecular processes regulated during drought were shared among Miscanthus species and consistent with functional categories known to be critical during drought stress in model organisms. However, differences in the regulated genes, likely associated with ploidy and heterosis, highlighted the value of exploring its diversity for breeding.

scholarly journals A Practical Multifaceted Approach to Selecting Differentially Expressed Genes

2007 ◽  
Vol 3 ◽  
pp. 117693510700300
Author(s):  
Yingye Zheng ◽  
Margaret Pepe
Keyword(s):  
Differential Expression ◽  
Gene Selection ◽  
Error Rates ◽  
Cancer Prognosis ◽  
Differentially Expressed ◽  
Expression Array ◽  
Statistical Research ◽  
P Values ◽  
Control Error ◽  
Strength Of Evidence

Consider a gene expression array study comparing two groups of subjects where the goal is to explore a large number of genes in order to select for further investigation a subset that appear to be differently expressed. There has been much statistical research into the development of formal methods for designating genes as differentially expressed. These procedures control error rates such as the false detection rate or family wise error rate. We contend however that other statistical considerations are also relevant to the task of gene selection. These include the extent of differential expression and the strength of evidence for differential expression at a gene. Using real and simulated data we first demonstrate that a proper exploratory analysis should evaluate these aspects as well as decision rules that control error rates. We propose a new measure called the mp-value that quantifies strength of evidence for differential expression. The mp-values are calculated with a resampling based algorithm taking into account the multiplicity and dependence encountered in microarray data. In contrast to traditional p-values our mp-values do not depend on specification of a decision rule for their definition. They are simply descriptive in nature. We contrast the mp-values with multiple testing p-values in the context of data from a breast cancer prognosis study and from a simulation model.

Screening candidate microR-15a- IRAK2 regulatory pairs for predicting the response to Staphylococcus aureus-induced mastitis in dairy cows

2019 ◽  
Vol 86 (4) ◽  
pp. 425-431 ◽  
Author(s):  
Zhi Chen ◽  
Jingpeng Zhou ◽  
Xiaolong Wang ◽  
Yang Zhang ◽  
Xubin Lu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Differential Expression ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Interleukin 1 ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Expression Of Genes ◽  
Chinese Holstein Cows ◽  
Reporter Assays

AbstractWe established a mastitis model using exogenous infection of the mammary gland of Chinese Holstein cows with Staphylococcus aureus and extracted total RNA from S. aureus-infected and healthy mammary quarters. Differential expression of genes due to mastitis was evaluated using Affymetrix technology and results revealed a total of 1230 differentially expressed mRNAs. A subset of affected genes was verified via Q-PCR and pathway analysis. In addition, Solexa high-throughput sequencing technology was used to analyze profiles of miRNA in infected and healthy quarters. These analyses revealed a total of 52 differentially expressed miRNAs. A subset of those results was verified via Q-PCR. Bioinformatics techniques were used to predict and analyze the correlations among differentially expressed miRNA and mRNA. Results revealed a total of 329 pairs of negatively associated miRNA/mRNA, with 31 upregulated pairs of mRNA and 298 downregulated pairs of mRNA. Differential expression of miR-15a and interleukin-1 receptor-associated kinase-like 2 (IRAK2), were evaluated by western blot and luciferase reporter assays. We conclude that miR-15a and miR-15a target genes (IRAK2) constitute potential miRNA–mRNA regulatory pairs for use as biomarkers to predict a mastitis response.

scholarly journals Integration of mRNA and miRNA Analysis Reveals the Molecular Mechanism of Cotton Response to Salt Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Zhan ◽  
Yangyang Diao ◽  
Guo Yin ◽  
Muhammad Sajjad ◽  
Xi Wei ◽  
...  
Keyword(s):  
Salt Stress ◽  
Differential Expression ◽  
Signal Transduction Pathway ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Regulatory Relationship ◽  
Significant Differential Expression ◽  
Amplification Bias ◽  
Before And After ◽  
Increased Sensitivity

To identify the regulatory network of known and novel microRNAs (miRNAs) and their targets responding to salt stress, a combined analysis of mRNA libraries, small RNA libraries, and degradome libraries were performed. In this study, we used unique molecular identifiers (UMIs), which are more sensitive, accurate, and reproducible than traditional methods of sequencing, to quantify the number of molecules and correct for amplification bias. We identified a total of 312 cotton miRNAs using seedlings at 0, 1, 3, and 6 h after NaCl treatment, including 80 known ghr-miRNAs and 232 novel miRNAs and found 155 miRNAs that displayed significant differential expression under salt stress. Among them, fifty-nine differentially expressed miRNAs were simultaneously induced in two or three tissues, while 66, 11, and 19 were specifically expressed in the roots, leaves, and stems, respectively. It is indicated there were different populations of miRNAs against salt stress in roots, leaves and stems. 399 candidate targets of salt-induced miRNAs showed significant differential expression before and after salt treatment, and 72 targets of 25 miRNAs were verified by degradome sequencing data. Furthermore, the regulatory relationship of miRNA-target gene was validated experimentally via 5′RLM-RACE, proving our data reliability. Gene ontology and KEGG pathway analysis found that salt-responsive miRNA targets among the differentially expressed genes were significantly enriched, and mainly involved in response to the stimulus process and the plant hormone signal transduction pathway. Furthermore, the expression levels of newly identified miRNA mir1 and known miRNAs miR390 and miR393 gradually decreased when subjected to continuous salt stress, while overexpression of these miRNAs both increased sensitivity to salt stress. Those newly identified miRNAs and mRNA pairs were conducive to genetic engineering and better understanding the mechanisms responding to salt stress in cotton.

scholarly journals Differential expression of cyclin A2 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells ◽  
Cyclin A2

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin A2, CCNA2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CCNA2 was also differentially expressed in bulk tumor in human breast cancer (3). CCNA2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CCNA2 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of CCNA2 was correlated with overall survival in patients with basal-like 1, basal-like 2, and mesenchymal subtype disease. CCNA2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

Sign in / Sign up

Export Citation Format

Share Document