scholarly journals Lineage‐specific sequence evolution and exon edge conservation partially explain the relationship between evolutionary rate and expression level in A. thaliana

2015 ◽  
Vol 24 (12) ◽  
pp. 3093-3106 ◽  
Author(s):  
Stephen J. Bush ◽  
Paula X. Kover ◽  
Araxi O. Urrutia
Keyword(s):  
Evolutionary Rate ◽  
Expression Level ◽  
Sequence Evolution ◽  
Specific Sequence ◽  
The Relationship

scholarly journals Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites

2014 ◽  
Author(s):  
Julian Echave ◽  
Eleisha L. Jackson ◽  
Claus O. Wilke
Keyword(s):  
Evolutionary Rate ◽  
Biophysical Model ◽  
Rate Variation ◽  
Sequence Evolution ◽  
Stress Model ◽  
Specific Sequence ◽  
Active Structure ◽  
Stability Model ◽  
The Stability ◽  
The Relationship

AbstractEvolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins (ΔΔG) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a “stability model” generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as does an alternative, recently proposed “stress model” that explains evolutionary-rate variation among sites in terms of the excess energy needed for mutants to adopt the correct active structure (ΔΔG*). The two models make distinct predictions, though, and for some proteins the stability model outperforms the stress model and vice versa. We conclude that both stability and stress constrain site-specific sequence evolution in proteins.

scholarly journals The missing expression level-evolutionary rate anticorrelation in viruses does not support protein function as a main constraint on sequence evolution

2021 ◽  
Author(s):  
Changshuo Wei ◽  
Yan-Ming Chen ◽  
Ying Chen ◽  
Wenfeng Qian
Keyword(s):  
Protein Function ◽  
Viral Protein ◽  
Evolutionary Biology ◽  
Evolutionary Rate ◽  
Purifying Selection ◽  
Endogenous Retroviruses ◽  
Expression Level ◽  
Sequence Evolution ◽  
Virus Species ◽  
Selective Constraints

Abstract One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, because it scales with the extent of selective constraints imposed on a protein, leading to the well-known negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). Selective constraints have been hypothesized to entail the maintenance of protein function, the avoidance of cytotoxicity caused by protein misfolding or nonspecific protein-protein interactions, or both. However, empirical tests evaluating the relative importance of these hypotheses remain scarce, likely due to the non-trivial difficulties in distinguishing the effect of a deleterious mutation on a protein’s function vs. its cytotoxicity. We realized that examining the sequence evolution of viral proteins could overcome this hurdle. It is because purifying selection against mutations in a viral protein that result in cytotoxicity per se is likely relaxed, while purifying selection against mutations that impair viral protein function persists. Multiple analyses of SARS-CoV-2 and nine other virus species revealed a complete absence of any E-R anticorrelation. As a control, the E-R anticorrelation does exist in human endogenous retroviruses where purifying selection against cytotoxicity is present. Taken together, these observations do not support the maintenance of protein function as the main constraint on protein sequence evolution in cellular organisms.

scholarly journals The Analysis of PTPN6 for Bladder Cancer: An Exploratory Study Based on TCGA

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chengquan Shen ◽  
Jing Liu ◽  
Jirong Wang ◽  
Xiaokun Yang ◽  
Haitao Niu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Survival Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Tyrosine Phosphatase ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Pathologic Features ◽  
The Relationship

PTPN6 (protein tyrosine phosphatase nonreceptor type 6), a tyrosine phosphatase, is known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Previous studies have demonstrated that PTPN6 expression is relatively elevated in several malignancies. However, the role of PTPN6 in bladder cancer (BC) remains unclear. The purpose of this study was to explore the prognostic value of PTPN6 in BC. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify the expression level of PTPN6 in BC. The relationship between clinical pathologic features and PTPN6 were analyzed with the Wilcoxon signed-rank test. The prognostic and predictive value of PTPN6 was evaluated by survival analysis and nomogram. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential molecular mechanisms of PTPN6 in BC. Finally, Tumor Immune Estimation Resource (TIMER) was applied to investigate the relationship between PTPN6 and immune cell infiltration in the tumor microenvironment. Results indicated that PTPN6 was overexpressed in BC tissues compared with normal bladder tissues and was significantly correlated with grade, stage, T, and N. Survival analysis showed that low expression of PTPN6 was significantly related to the poor overall survival (OS) in BC patients. Coexpression analysis showed that PTPN6 and TNFRSF14 (Tumor necrosis factor receptor superfamily member 14) have a close correlation in BC. GSEA showed that multiple cancer-associated signaling pathways are differentially enriched in the PTPN6 high expression phenotype. Moreover, the expression level of PTPN6 was positively associated with the infiltration of B cells, CD4+T cells, dendritic cells, and neutrophils and negatively associated with CD8+ T cells and macrophages in BC. In conclusion, we identified that PTPN6 may be a novel prognostic biomarker in BC based on the TCGA database. Further clinical trials are needed to confirm our observations and mechanisms underlying the prognostic value of PTPN6 in BC also deserve further experimental exploration.

scholarly journals Expression Level of Annexin A1 Contributes to the Evaluation of the Disease Progression and Treatment Effect of Lung Adenocarcinoma: A New Perspective from Retrospective Analysis

2021 ◽  
Author(s):  
Biaoxue Rong ◽  
Hongling Yan ◽  
Ge Wu ◽  
Kai Li ◽  
Min Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Disease Progression ◽  
Treatment Effect ◽  
Expression Level ◽  
Annexin A1 ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Cancer Tissues ◽  
The Relationship

Abstract Background: Increased Annexin A1 has been showed to be related to malignant biological characteristics of tumors; the aim of this study was to evaluate the relationship between the expression level of Annexin A1 and the disease progression and treatment effect of lung adenocarcinoma (LAC). Methods: The expression level of Annexin A1 in LAC tissues and cells was detected by the methods of immunohistochemistry, Real time-PCR and western blotting. The relationship between the expression of Annexin A1 and the disease progression and treatment effect of LAC was evaluated by descriptive statistics, T test and Chi-square test. Results: The protein expression of Annexin A1 was higher in lung cancer tissues and cells than that in normal tissues and 16 human bronchial epithelial (16HBE) cells (p<0.05). The level of Annexin A1 mRNA was higher in lung cancer tissues than that in normal tissues (p<0.05). The increase of Annexin A1 protein and mRNA was associated with the lymph node metastasis, advanced clinical stage (p<0.05). However, surgical resection and chemotherapy for LAC down-regulated the serum concentration of Annexin A1 in patients (p<0.05).Conclusions: Increased Annexin A1 protein and mRNA in LAC tissues correlate with the poor differentiation, lymph node metastasis and advanced stage of LAC. Surgical resection and chemotherapy for LAC down-regulate the serum concentration of Annexin A1 in patients. The results indicate that expression level of Annexin A1 contributes to the evaluation of the disease progression and treatment effect of LAC.

scholarly journals Immune Cell Landscape in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yang Yang ◽  
Wei He ◽  
Zi-rui Wang ◽  
Yu-jiao Wang ◽  
Lan-lan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Univariate Analysis ◽  
Molecular Therapy ◽  
Expression Level ◽  
Regulatory Factors ◽  
Normal Tissues ◽  
The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

Wilms Tumor 1 (WT1) mRNA Expression Level at Diagnosis Is a Significant Prognostic Marker in Elderly Patients with Myelodysplastic Syndrome

2016 ◽  
Vol 137 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Joji Nagasaki ◽  
Yasutaka Aoyama ◽  
Masayuki Hino ◽  
Kentaro Ido ◽  
Hiroyoshi Ichihara ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Myelodysplastic Syndrome ◽  
Mrna Expression ◽  
Prognostic Marker ◽  
Wilms Tumor ◽  
High Expression ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Wilms Tumor 1 ◽  
The Relationship

Background/Aims: A high expression of Wilms tumor 1 (WT1) mRNA occurs in most cases of acute leukemia and myelodysplastic syndrome (MDS). Although there are many reports suggesting that acute myeloid leukemia patients with high expression levels of WT1 mRNA have a relatively poor long-term survival, there are few reports addressing the relationship between WT1 levels and prognosis in MDS. Methods: We retrospectively analyzed 42 elderly patients with MDS whose WT1 levels at diagnosis were available, and we assessed the relationships between WT1 levels in peripheral blood and preexisting prognostic factors such as World Health Organization prognostic scores and Revised International Prognostic Scoring System risk categories, bone marrow blast percentages, and chromosomal abnormalities linked to a poor prognosis. We also evaluated the relationship between WT1 levels and prognosis. Results:WT1 levels were significantly different between high- and low-risk MDS patients (p < 0.05). There was a trend towards a significant difference between those with and those without poor prognostic chromosomal rearrangements (p = 0.051). Moreover, the overall survival and progression-free survival were significantly worse in elderly patients with higher levels of WT1 (p = 0.00039 and p = 0.00077, respectively). Conclusions: The WT1 mRNA expression level at diagnosis may be a significant independent prognostic marker for elderly patients with MDS.

scholarly journals Epistatic contributions promote the unification of incompatible models of neutral molecular evolution

2020 ◽  
Vol 117 (11) ◽  
pp. 5873-5882 ◽  
Author(s):  
Jose Alberto de la Paz ◽  
Charisse M. Nartey ◽  
Monisha Yuvaraj ◽  
Faruck Morcos
Keyword(s):  
Structural Information ◽  
Stokes Shift ◽  
Neutral Evolution ◽  
Emergent Properties ◽  
Sequence Evolution ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Analysis Methodology ◽  
The Relationship

We introduce a model of amino acid sequence evolution that accounts for the statistical behavior of real sequences induced by epistatic interactions. We base the model dynamics on parameters derived from multiple sequence alignments analyzed by using direct coupling analysis methodology. Known statistical properties such as overdispersion, heterotachy, and gamma-distributed rate-across-sites are shown to be emergent properties of this model while being consistent with neutral evolution theory, thereby unifying observations from previously disjointed evolutionary models of sequences. The relationship between site restriction and heterotachy is characterized by tracking the effective alphabet dynamics of sites. We also observe an evolutionary Stokes shift in the fitness of sequences that have undergone evolution under our simulation. By analyzing the structural information of some proteins, we corroborate that the strongest Stokes shifts derive from sites that physically interact in networks near biochemically important regions. Perspectives on the implementation of our model in the context of the molecular clock are discussed.

scholarly journals Accelerated Immunodeficiency-associated Vaccine-derived Poliovirus Serotype 3 Sequence Evolution Rate in an 11-week-old Boy With X-linked Agammaglobulinemia and Perinatal Human Immunodeficiency Virus Exposure

2019 ◽  
Vol 70 (1) ◽  
pp. 132-135 ◽  
Author(s):  
Sabelle Jallow ◽  
Jo M Wilmshurst ◽  
Wayne Howard ◽  
Julie Copelyn ◽  
Lerato Seakamela ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
B Cell ◽  
Evolutionary Rate ◽  
Evolution Rate ◽  
Early Age ◽  
Sequence Evolution ◽  
Perinatal Exposure ◽  
Immunodeficiency Virus ◽  
Virus Exposure

Abstract Primary B-cell immunodeficiencies are risk factors for the generation of vaccine-derived polioviruses. We report immunodeficiency-associated vaccine-derived poliovirus serotype 3 in an 11-week-old boy with X-linked agammaglobulinemia. Unique characteristics of this case include early age of presentation, high viral evolutionary rate, and the child’s perinatal exposure to human immunodeficiency virus.

scholarly journals Evolution of the Unique Anuran Pelvic and Hind limb Skeleton in Relation to Microhabitat, Locomotor Mode, and Jump Performance

2020 ◽  
Vol 60 (5) ◽  
pp. 1330-1345 ◽  
Author(s):  
Shannon M Buttimer ◽  
Natasha Stepanova ◽  
Molly C Womack
Keyword(s):  
Hind Limb ◽  
Evolutionary Rate ◽  
Morphological Changes ◽  
Body Plan ◽  
Individual Species ◽  
Museum Collections ◽  
Jump Performance ◽  
Anuran Species ◽  
The Relationship ◽  
3D Landmarks

Abstract Anurans (frogs and toads) have a unique pelvic and hind limb skeleton among tetrapods. Although their distinct body plan is primarily associated with saltation, anuran species vary in their primary locomotor mode (e.g., walkers, hoppers, jumpers, and swimmers) and are found in a wide array of microhabitats (e.g., burrowing, terrestrial, arboreal, and aquatic) with varying functional demands. Given their largely conserved body plan, morphological adaptation to these diverse niches likely results from more fine-scale morphological change. Our study determines how shape differences in Anura’s unique pelvic and hind limb skeletal structures vary with microhabitat, locomotor mode, and jumping ability. Using microCT scans of preserved specimens from museum collections, we added 3D landmarks to the pelvic and hind limb skeleton of 230 anuran species. In addition, we compiled microhabitat and locomotor data from the literature for these species that span 52 of the 55 families of frogs and ∼210 million years of anuran evolution. Using this robust dataset, we examine the relationship between pelvic and hind limb morphology and phylogenetic history, allometry, microhabitat, and locomotor mode. We find pelvic and hind limb changes associated with shifts in microhabitat (“ecomorphs”) and locomotor mode (“locomorphs”) and directly relate those morphological changes to the jumping ability of individual species. We also reveal how individual bones vary in evolutionary rate and their association with phylogeny, body size, microhabitat, and locomotor mode. Our findings uncover previously undocumented morphological variation related to anuran ecological and locomotor diversification and link that variation to differences in jumping ability among species.

scholarly journals ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuqi Xiang ◽  
Liyu Liu ◽  
Ying Wang ◽  
Bo Li ◽  
Jinwu Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Matrix Metalloproteinase ◽  
Gene Family ◽  
Tumor Progression ◽  
Molecular Mechanism ◽  
Cell Invasion ◽  
Expression Level ◽  
Invasion And Metastasis ◽  
Direct Association ◽  
The Relationship

Abstract Background The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. Methods In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. Results Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. Conclusion Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

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