Genomic evidence of adaptive evolution in the reptilian SOCS gene family

The suppressor of the cytokine signaling (SOCS) family of proteins play an essential role in inhibiting cytokine receptor signaling by regulating immune signal pathways. Although SOCS gene functions have been examined extensively, no comprehensive study has been performed on this gene family’s molecular evolution in reptiles. In this study, we identified eight canonical SOCS genes using recently-published reptilian genomes. We used phylogenetic analysis to determine that the SOCS genes had highly conserved evolutionary dynamics that we classified into two types. We identified positive SOCS4 selection signals in whole reptile lineages and SOCS2 selection signals in the crocodilian lineage. Selective pressure analyses using the branch model and Z-test revealed that these genes were under different negative selection pressures compared to reptile lineages. We also concluded that the nature of selection pressure varies across different reptile lineages on SOCS3, and the crocodilian lineage has experienced rapid evolution. Our results may provide a theoretical foundation for further analyses of reptilian SOCS genes’ functional and molecular mechanisms, as well as their roles in reptile growth and development.

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Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes

Nature Communications ◽

10.1038/s41467-021-24982-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Joel M. J. Tan ◽

Monica E. Garner ◽

James M. Regeimbal ◽

Catherine J. Greene ◽

Jorge D. Rojas Márquez ◽

...

Keyword(s):

Antibacterial Activity ◽

Molecular Mechanisms ◽

Immune Cell ◽

Transmembrane Protein ◽

Foodborne Pathogen ◽

Systemic Infection ◽

Cytokine Signaling ◽

Type I ◽

Type I Ifn ◽

Antiviral Protein

AbstractThe type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.

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Cancer cachexia: molecular mechanism and pharmacological management

Biochemical Journal ◽

10.1042/bcj20201009 ◽

2021 ◽

Vol 478 (9) ◽

pp. 1663-1688

Author(s):

Yonghua Li ◽

Huan Jin ◽

Yibing Chen ◽

Ting Huang ◽

Yanjun Mi ◽

...

Keyword(s):

Adipose Tissue ◽

Cancer Cachexia ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Life Quality ◽

Signal Pathways ◽

Pharmacological Management ◽

Early Phase Trials ◽

Molecular Substrates ◽

Underlying Mechanisms

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

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NNK-Induced Lung Tumors: A Review of Animal Model

Journal of Oncology ◽

10.1155/2011/635379 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Hua-Chuan Zheng ◽

Yasuo Takano

Keyword(s):

Lung Cancer ◽

Animal Model ◽

Animal Models ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Genetic Mutation ◽

Lung Tumors ◽

Chemotherapeutic Agents ◽

Signal Pathways ◽

Lung Carcinogenesis

The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models.

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Reverse transcriptase sequences from mulberry LTR retrotransposons: characterization analysis

Open Life Sciences ◽

10.1515/biol-2017-0031 ◽

2017 ◽

Vol 12 (1) ◽

pp. 266-276

Author(s):

Bi Ma ◽

Lulu Kuang ◽

Youchao Xin ◽

Fei Hou ◽

Ningjia He

Keyword(s):

Reverse Transcriptase ◽

Evolutionary Dynamics ◽

Selective Pressure ◽

Sequence Divergence ◽

Degenerate Primers ◽

Random Mutation ◽

Functional Studies ◽

Study Support ◽

Element Transfer

AbstractCopia and Gypsy play important roles in structural, functional and evolutionary dynamics of plant genomes. In this study, a total of 106 and 101, Copia and Gypsy reverse transcriptase (rt) were amplified respectively in the Morus notabilis genome using degenerate primers. All sequences exhibited high levels of heterogeneity, were rich in AT and possessed higher sequence divergence of Copia rt in comparison to Gypsy rt. Two reasons are likely to account for this phenomenon: a) these elements often experience deletions or fragmentation by illegitimate or unequal homologous recombination in the transposition process; b) strong purifying selective pressure drives the evolution of these elements through “selective silencing” with random mutation and eventual deletion from the host genome. Interestingly, mulberry rt clustered with other rt from distantly related taxa according to the phylogenetic analysis. This phenomenon did not result from horizontal transposable element transfer. Results obtained from fluorescence in situ hybridization revealed that most of the hybridization signals were preferentially concentrated in pericentromeric and distal regions of chromosomes, and these elements may play important roles in the regions in which they are found. Results of this study support the continued pursuit of further functional studies of Copia and Gypsy in the mulberry genome.

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Seed Banks Alter the Rate and Direction of Molecular Evolution in Bacillus subtilis

10.1101/2021.10.05.463161 ◽

2021 ◽

Author(s):

William R. Shoemaker ◽

Evgeniya Polezhaeva ◽

Kenzie B. Givens ◽

Jay T. Lennon

Keyword(s):

Bacillus Subtilis ◽

Molecular Evolution ◽

Seed Bank ◽

Negative Selection ◽

Evolutionary Dynamics ◽

Genetic Manipulation ◽

Seed Banks ◽

Rate Of Molecular Evolution ◽

Over Time ◽

Growth And Reproduction

Fluctuations in the availability of resources constrains the growth and reproduction of individuals, which in turn effects the evolution of their respective populations. Many organisms are able to respond to fluctuations by entering a reversible state of reduced metabolic activity, a phenomenon known as dormancy. This pool of dormant individuals (i.e., a seed bank) does not reproduce and is expected to act as an evolutionary buffer, though it is difficult to observe this effect directly over an extended evolutionary timescale. Through genetic manipulation, we analyze the molecular evolutionary dynamics of Bacillus subtilis populations in the presence and absence of a seed bank over 700 days. We find that the ability to enter a dormant state increases the accumulation of genetic diversity over time and alters the trajectory of mutations, findings that are recapitulated using simulations based on a simple mathematical model. While the ability to form a seed bank does not alter the degree of negative selection, we find that it consistently alters the direction of molecular evolution across genes. Together, these results show that the ability to form a seed bank affects the direction and rate of molecular evolution over an extended evolutionary timescale.

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Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network

10.1101/2020.03.17.995621 ◽

2020 ◽

Author(s):

Miriam Pagin ◽

Simone Giubbolini ◽

Cristiana Barone ◽

Gaia Sambruni ◽

Yanfen Zhu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cytokine Signaling ◽

Normal Brain ◽

Suppressor Of Cytokine Signaling ◽

Self Renewal ◽

Upstream Regulator ◽

Socs3 Expression ◽

Pharmacological Manipulations

AbstractThe Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSC). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, individually or in combination, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2). Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Further, Fos requirement for efficient long-term proliferation was demonstrated by the strong reduction of NSC clones capable of long-term expansion following CRISPR/Cas9-mediated Fos inactivation. Previous work showed that the Suppressor of cytokine signaling 3 (Socs3) gene is strongly downregulated following Sox2 deletion, and its reexpression by lentiviral transduction rescues long-term NSC proliferation. Fos appears to be an upstream regulator of Socs3, possibly together with Jun and Egr2; indeed, Sox2 reexpression in Sox2-deleted NSC progressively activates both Fos and Socs3 expression; in turn, Fos transduction activates Socs3 expression. Based on available SOX2 ChIPseq and ChIA-PET data, as well as results from the literature, we propose a model whereby Sox2 is a direct activator of both Socs3 and Fos, as well as possibly Jun and Egr2; in turn, Fos, Jun and Egr2 may activate Socs3. These results provide the basis for developing a model of a network of interactions, regulating critical effectors of NSC proliferation and long-term maintenance.Significance statementProliferation and maintenance of NSC are essential during normal brain development, and, postnatally, for the maintenance of hippocampal function and memory until advanced age. Little is known about the molecular mechanisms that maintain the critical aspects of NSC biology (quiescence and proliferation) in postnatal age. Our work provides a methodology, transduction of genes deregulated following Sox2 deletion, that allows to test many candidate genes for their ability to sustain NSC proliferation. In principle, this may have interesting implications for identifying targets for pharmacological manipulations.

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The Role of Tumor-related LncRNA PART1 in cancer

Current Pharmaceutical Design ◽

10.2174/1381612827666210705161955 ◽

2021 ◽

Vol 27 ◽

Author(s):

Jinlan Chen ◽

Enqing Meng ◽

Yexiang Lin ◽

Yujie Shen ◽

Chengyu Hu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Malignant Tumors ◽

Migration And Invasion ◽

Signal Pathways ◽

Toll Like Receptor ◽

Non Coding Rna ◽

Regulated Expression ◽

The One ◽

Long Non Coding Rna

Background: As we all know, long non-coding RNA (lncRNA) affects tumor progression, which has caused a great upsurge in recent years. It can also affect the growth, migration, and invasion of tumors. When we refer to the abnormal expression of lncRNA, we will find it associated with malignant tumors. In addition, lncRNA has been proved to be a key targeted gene for the treatment of some diseases. PART1, a member of lncRNA, has been reported as a regulator in the process of tumor occurrence and development. This study aims to reveal the biological functions, specific mechanisms, and clinical significance of PART1 in various tumor cells. Methods: Through the careful search of PUBMED, the mechanisms of the effect of PART1 on tumorigenesis and development are summarized. Results: On the one hand, the up-regulated expression of PART1 plays a tumor-promoting role in tumors, including lung cancer, prostate cancer, bladder cancer and so on. On the other hand, PART1 is down-regulated in gastric cancer, glioma and other tumors to play a tumor inhibitory role. In addition, PART1 regulates tumor growth mainly by targeting microRNA such as miR-635, directly regulating the expression of proteins such as FUS/EZH2, affecting signal pathways such as the Toll-like receptor pathway, or regulating immune cells. Conclusion: PART1 is closely related to tumors by regulating a variety of molecular mechanisms. In addition, PART1 can be used as a clinical marker for the early diagnosis of tumors and plays an important role in tumor-targeted therapy.

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Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways

Antioxidants ◽

10.3390/antiox8090395 ◽

2019 ◽

Vol 8 (9) ◽

pp. 395 ◽

Cited By ~ 5

Author(s):

Zi Wang ◽

Weinan Hao ◽

Junnan Hu ◽

Xiaojie Mi ◽

Ye Han ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

B Cell Lymphoma ◽

Inflammatory Factors ◽

Signal Pathways ◽

Dependent Manner ◽

Beneficial Effects

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway.

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PRDM9 Diversity at Fine Geographical Scale Reveals Contrasting Evolutionary Patterns and Functional Constraints in Natural Populations of House Mice

Molecular Biology and Evolution ◽

10.1093/molbev/msz091 ◽

2019 ◽

Vol 36 (8) ◽

pp. 1686-1700 ◽

Cited By ~ 4

Author(s):

Covadonga Vara ◽

Laia Capilla ◽

Luca Ferretti ◽

Alice Ledda ◽

Rosa A Sánchez-Guillén ◽

...

Keyword(s):

Reproductive Isolation ◽

Evolutionary Biology ◽

Evolutionary Dynamics ◽

Rapid Evolution ◽

Natural Populations ◽

Global Scale ◽

House Mice ◽

Functional Constraints ◽

Evolutionary Patterns ◽

Data Set

Abstract One of the major challenges in evolutionary biology is the identification of the genetic basis of postzygotic reproductive isolation. Given its pivotal role in this process, here we explore the drivers that may account for the evolutionary dynamics of the PRDM9 gene between continental and island systems of chromosomal variation in house mice. Using a data set of nearly 400 wild-caught mice of Robertsonian systems, we identify the extent of PRDM9 diversity in natural house mouse populations, determine the phylogeography of PRDM9 at a local and global scale based on a new measure of pairwise genetic divergence, and analyze selective constraints. We find 57 newly described PRDM9 variants, this diversity being especially high on Madeira Island, a result that is contrary to the expectations of reduced variation for island populations. Our analysis suggest that the PRDM9 allelic variability observed in Madeira mice might be influenced by the presence of distinct chromosomal fusions resulting from a complex pattern of introgression or multiple colonization events onto the island. Importantly, we detect a significant reduction in the proportion of PRDM9 heterozygotes in Robertsonian mice, which showed a high degree of similarity in the amino acids responsible for protein–DNA binding. Our results suggest that despite the rapid evolution of PRDM9 and the variability detected in natural populations, functional constraints could facilitate the accumulation of allelic combinations that maintain recombination hotspot symmetry. We anticipate that our study will provide the basis for examining the role of different PRDM9 genetic backgrounds in reproductive isolation in natural populations.

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Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny

Molecular Biology and Evolution ◽

10.1093/molbev/msy005 ◽

2018 ◽

Vol 35 (4) ◽

pp. 925-941 ◽

Cited By ~ 31

Author(s):

Kevin H -C Wei ◽

Sarah E Lower ◽

Ian V Caldas ◽

Trevor J S Sless ◽

Daniel A Barbash ◽

...

Keyword(s):

Evolutionary Dynamics ◽

Rapid Evolution ◽

Single Mutation ◽

Closely Related Species ◽

Interspecific Differences ◽

Limited Sampling ◽

Drosophila Phylogeny ◽

Males And Females ◽

Species Specific ◽

Turn Over

Abstract Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through nonallelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly. However, limited sampling has prevented detailed understanding of their evolutionary dynamics. Here, we characterize simple satellites from whole-genome sequences generated from males and females of nine Drosophila species, spanning 40 Ma of evolution. We show that PCR-free library preparation and postsequencing GC-correction better capture satellite quantities than conventional methods. We find that over half of the 207 simple satellites identified are species-specific, consistent with previous descriptions of their rapid evolution. Based on a maximum parsimony framework, we determined that most interspecific differences are due to lineage-specific gains. Simple satellites gained within a species are typically a single mutation away from abundant existing satellites, suggesting that they likely emerge from existing satellites, especially in the genomes of satellite-rich species. Interestingly, unlike most of the other lineages which experience various degrees of gains, the lineage leading up to the satellite-poor D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing a counterpoint to the notion that simple satellites are universally rapidly evolving.

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