Retrotransposon- and microsatellite sequence-associated genomic changes in early generations of a newly synthesized allotetraploid Cucumis × hytivus Chen & Kirkbride

Background. Mechanical stress-induced cardiac remodeling that results in heart failure is characterized by transcriptional reprogramming of gene expression. However, a systematic study of genomic changes involved in this process has not been performed to date. To investigate the genomic changes and underlying mechanism of cardiac remodeling, we collected and analyzed DNA microarray data for murine transverse aortic constriction (TAC) and human aortic stenosis (AS) from the Gene Expression Omnibus database and the European Bioinformatics Institute. Methods and Results. The differential expression genes (DEGs) across the datasets were merged. The Venn diagrams showed that the number of intersections for early and late cardiac remodeling was 74 and 16, respectively. Gene ontology and protein–protein interaction network analysis showed that metabolic changes, cell differentiation and growth, cell cycling, and collagen fibril organization accounted for a great portion of the DEGs in the TAC model, while in AS patients’ immune system signaling and cytokine signaling displayed the most significant changes. The intersections between the TAC model and AS patients were few. Nevertheless, the DEGs of the two species shared some common regulatory transcription factors (TFs), including SP1, CEBPB, PPARG, and NFKB1, when the heart was challenged by applied mechanical stress. Conclusions. This study unravels the complex transcriptome profiles of the heart tissues and highlighting the candidate genes involved in cardiac remodeling induced by mechanical stress may usher in a new era of precision diagnostics and treatment in patients with cardiac remodeling.

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Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Cancers ◽

10.3390/cancers13133272 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3272

Author(s):

Lauren K. Jillson ◽

Gabriel A. Yette ◽

Teemu D. Laajala ◽

Wayne D. Tilley ◽

James C. Costello ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Targeted Therapies ◽

Meta Analysis ◽

Therapy Resistance ◽

Androgen Receptor Signaling ◽

Genomic Changes ◽

Risk Patients ◽

Important Pathway ◽

Therapy Option

While many prostate cancer (PCa) cases remain indolent and treatable, others are aggressive and progress to the metastatic stage where there are limited curative therapies. Androgen receptor (AR) signaling remains an important pathway for proliferative and survival programs in PCa, making disruption of AR signaling a viable therapy option. However, most patients develop resistance to AR-targeted therapies or inherently never respond. The field has turned to PCa genomics to aid in stratifying high risk patients, and to better understand the mechanisms driving aggressive PCa and therapy resistance. While alterations to the AR gene itself occur at later stages, genomic changes at the primary stage can affect the AR axis and impact response to AR-directed therapies. Here, we review common genomic alterations in primary PCa and their influence on AR function and activity. Through a meta-analysis of multiple independent primary PCa databases, we also identified subtypes of significantly co-occurring alterations and examined their combinatorial effects on the AR axis. Further, we discussed the subsequent implications for response to AR-targeted therapies and other treatments. We identified multiple primary PCa genomic subtypes, and given their differing effects on AR activity, patient tumor genetics may be an important stratifying factor for AR therapy resistance.

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Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

Genes ◽

10.3390/genes10110901 ◽

2019 ◽

Vol 10 (11) ◽

pp. 901 ◽

Cited By ~ 10

Author(s):

Asiya Gusa ◽

Sue Jinks-Robertson

Keyword(s):

Fungal Pathogens ◽

Repetitive Sequences ◽

Pathogenic Fungi ◽

Genetic Alterations ◽

Fungal Species ◽

Chronic Infections ◽

Yeast Saccharomyces Cerevisiae ◽

Genomic Changes ◽

Break Site ◽

Repair Mechanisms

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

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Telomeric DNA sequences in beetle taxa vary with species richness

Scientific Reports ◽

10.1038/s41598-021-92705-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniela Prušáková ◽

Vratislav Peska ◽

Stano Pekár ◽

Michal Bubeník ◽

Lukáš Čížek ◽

...

Keyword(s):

Species Richness ◽

Dna Sequences ◽

Genome Instability ◽

Telomeric Sequence ◽

Dna Repeats ◽

Telomeric Dna ◽

Common Pattern ◽

Telomeric Sequences ◽

Genomic Changes ◽

Protective Structures

AbstractTelomeres are protective structures at the ends of eukaryotic chromosomes, and disruption of their nucleoprotein composition usually results in genome instability and cell death. Telomeric DNA sequences have generally been found to be exceptionally conserved in evolution, and the most common pattern of telomeric sequences across eukaryotes is (TxAyGz)n maintained by telomerase. However, telomerase-added DNA repeats in some insect taxa frequently vary, show unusual features, and can even be absent. It has been speculated about factors that might allow frequent changes in telomere composition in Insecta. Coleoptera (beetles) is the largest of all insect orders and based on previously available data, it seemed that the telomeric sequence of beetles varies to a great extent. We performed an extensive mapping of the (TTAGG)n sequence, the ancestral telomeric sequence in Insects, across the main branches of Coleoptera. Our study indicates that the (TTAGG)n sequence has been repeatedly or completely lost in more than half of the tested beetle superfamilies. Although the exact telomeric motif in most of the (TTAGG)n-negative beetles is unknown, we found that the (TTAGG)n sequence has been replaced by two alternative telomeric motifs, the (TCAGG)n and (TTAGGG)n, in at least three superfamilies of Coleoptera. The diversity of the telomeric motifs was positively related to the species richness of taxa, regardless of the age of the taxa. The presence/absence of the (TTAGG)n sequence highly varied within the Curculionoidea, Chrysomeloidea, and Staphylinoidea, which are the three most diverse superfamilies within Metazoa. Our data supports the hypothesis that telomere dysfunctions can initiate rapid genomic changes that lead to reproductive isolation and speciation.

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Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

Cancer Gene Therapy ◽

10.1038/s41417-020-00283-4 ◽

2021 ◽

Author(s):

Wenhui Li ◽

Wanjun Lei ◽

Xiaopei Chao ◽

Xiaochen Song ◽

Yalan Bi ◽

...

Keyword(s):

Copy Number ◽

Somatic Mutations ◽

Hpv Infection ◽

Copy Number Variations ◽

Cervical Adenocarcinoma ◽

Structural Variations ◽

Driver Genes ◽

Genetic Changes ◽

Genomic Changes ◽

Whole Exome

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

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Experimental evolution of gallium resistance in Escherichia coli

Evolution Medicine and Public Health ◽

10.1093/emph/eoz025 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 169-180

Author(s):

Joseph L Graves ◽

Akamu J Ewunkem ◽

Jason Ward ◽

Constance Staley ◽

Misty D Thomas ◽

...

Keyword(s):

Escherichia Coli ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Experimental Evolution ◽

Molecular Mechanisms ◽

Gallium Nitrate ◽

Whole Genome ◽

Mechanisms Of Resistance ◽

Genomic Changes ◽

K 12

Abstract Background and Objectives Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties. Methodology Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance. Results By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC →/→ yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ←; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD ←/→ entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF ←/→ yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance. Conclusions This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to an atom that mimics an essential micronutrient and shows the pleiotropic consequences associated with this adaptation. Lay summary We utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance.

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Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview

Genes and Environment ◽

10.1186/s41021-021-00187-1 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Iman Akhlaghipour ◽

Amir Reza Bina ◽

Mohammad Reza Abbaszadegan ◽

Meysam Moghbeli

Keyword(s):

Risk Factors ◽

Early Detection ◽

Tumor Progression ◽

Cancer Patients ◽

Early Detection Of Cancer ◽

Iranian Population ◽

Molecular Diagnostic ◽

Genomic Changes ◽

Incidence And Mortality ◽

Transcriptional Alterations

AbstractCancer is one of the main health challenges and leading causes of deaths in the world. Various environmental and genetic risk factors are associated with tumorigenesis. Epigenetic deregulations are also important risk factors during tumor progression which are reversible transcriptional alterations without any genomic changes. Various mechanisms are involved in epigenetic regulations such as DNA methylation, chromatin modifications, and noncoding RNAs. Cancer incidence and mortality have a growing trend during last decades among Iranian population which are significantly related to the late diagnosis. Therefore, it is required to prepare efficient molecular diagnostic panels for the early detection of cancer in this population. Promoter hyper methylation is frequently observed as an inhibitory molecular mechanism in various genes associated with DNA repair, cell cycle regulation, and apoptosis during tumor progression. Since aberrant promoter methylations have critical roles in early stages of neoplastic transformations, in present review we have summarized all of the aberrant methylations which have been reported during tumor progression among Iranian cancer patients. Aberrant promoter methylations are targetable and prepare novel therapeutic options for the personalized medicine in cancer patients. This review paves the way to introduce a non-invasive methylation specific panel of diagnostic markers for the early detection of cancer among Iranians.

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Evidence of gene nucleotide composition favoring replication and growth in a fastidious plant pathogen

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab076 ◽

2021 ◽

Author(s):

Andreina I Castillo ◽

Rodrigo P P Almeida

Keyword(s):

Plant Pathogen ◽

Geographic Origin ◽

Gc Content ◽

Nucleotide Composition ◽

Plant Host ◽

Mixed Effect ◽

Genomic Changes ◽

Evolutionary Forces ◽

Multiple Variables ◽

Vector Borne

Abstract Nucleotide composition (GC content) varies across bacteria species, genome regions, and specific genes. In Xylella fastidiosa, a vector-borne fastidious plant pathogen infecting multiple crops, GC content ranges between ∼51-52%; however, these values were gathered using limited genomic data. We evaluated GC content variations across X. fastidiosa subspecies fastidiosa (N = 194), subsp. pauca (N = 107), and subsp. multiplex (N = 39). Genomes were classified based on plant host and geographic origin; individual genes within each genome were classified based on gene function, strand, length, ortholog group, Core vs. Accessory, and Recombinant vs. Non-recombinant. GC content was calculated for each gene within each evaluated genome. The effects of genome and gene level variables were evaluated with a mixed effect ANOVA, and the marginal-GC content was calculated for each gene. Also, the correlation between gene-specific GC content vs. natural selection (dN/dS) and recombination/mutation (r/m) was estimated. Our analyses show that intra-genomic changes in nucleotide composition in X. fastidiosa are small and influenced by multiple variables. Higher AT-richness is observed in genes involved in replication and translation, and genes in the leading strand. In addition, we observed a negative correlation between high-AT and dN/dS in subsp. pauca. The relationship between recombination and GC content varied between core and accessory genes. We hypothesize that distinct evolutionary forces and energetic constraints both drive and limit these small variations in nucleotide composition.

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