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World Journal of Microbiology &... Jul 2020The fermentation of industrial bacteria encounters a serious problem in continuous culture, i.e. the production traits lose. However, current research on the mechanism... (Review)
Review
The fermentation of industrial bacteria encounters a serious problem in continuous culture, i.e. the production traits lose. However, current research on the mechanism of strain degeneration is not clear enough, and there are few methods to effectively control the degeneration. Under growth restriction, the mutation rate of fermentation strains increases. Many cellular processes and poor fermentation conditions can trigger the transposition of transposable elements, SOS response, and RpoS-controlled adaptive mutations, causing genetic instability. Genetic instability which resulted from point mutations and genomic rearrangements can be responsible for strain degeneration. This mini-review summarizes the degeneration phenomena and mechanisms in common industrial bacteria and highlights three mechanisms of strain degeneration, including the transposition of transposable elements, SOS response, and adaptive mutations. According to different mutation mechanisms, many promising strategies have been proposed to increase the stability and the yield of industrial strains, for example, developing platform strains free of insertion sequence to enhance the stability of recombinant plasmid, using SOS inhibitors to block the SOS response, and improving environmental tolerance capacity and fermentation conditions to reduce adaptive mutations.
Topics: DNA Transposable Elements; Fermentation; Genomic Instability; Industrial Microbiology; Mutation; Phenotype; Point Mutation; Recombination, Genetic
PubMed: 32681370
DOI: 10.1007/s11274-020-02901-7 -
Pest Management Science Nov 2023Fusarium pseudograminearum is one of the dominant pathogens of Fusarium crown rot (FCR) worldwide. Unfortunately, no fungicides have yet been registered for the control...
BACKGROUND
Fusarium pseudograminearum is one of the dominant pathogens of Fusarium crown rot (FCR) worldwide. Unfortunately, no fungicides have yet been registered for the control of FCR in wheat in China. Pydiflumetofen, a new-generation succinate dehydrogenase inhibitor, exhibits excellent inhibitory activity to Fusarium spp. A resistance risk assessment of F. pseudograminearum to pydiflumetofen and the resistance mechanism involved have not yet been investigated.
RESULTS
The median effective concentration (EC ) value of 103 F. pseudograminearum isolates to pydiflumetofen was 0.0162 μg mL , and the sensitivity exhibited a unimodal distribution. Four resistant mutants were generated by fungicide adaption, which possessed similar or impaired fitness compared to corresponding parental isolates based on the results of mycelial growth, conidiation, conidium germination rate, and virulence determination. Pydiflumetofen showed strong positive cross-resistance with cyclobutrifluram and fluopyram but no cross-resistance with carbendazim, phenamacril, tebuconazole, fludioxonil, or pyraclostrobin. Sequence alignment revealed that pydiflumetofen-resistant F. pseudograminearum mutants had two single-point mutations of A83V or R86K in FpSdhC . Molecular docking further confirmed that point mutation of A83V or R86K in FpSdhC could confer resistance of F. pseudograminearum to pydiflumetofen.
CONCLUSION
Fusarium pseudograminearum shows an overall moderate risk of developing resistance to pydiflumetofen, and point mutation FpSdhC or FpSdhC could confer pydiflumetofen resistance in F. pseudograminearum. This study provided vital data for monitoring the emergence of resistance and developing resistance management strategies for pydiflumetofen. © 2023 Society of Chemical Industry.
Topics: Point Mutation; Fusarium; Molecular Docking Simulation; Plant Diseases; Fungicides, Industrial
PubMed: 37326415
DOI: 10.1002/ps.7616 -
Nature Methods Mar 2019
Topics: Adenosine Deaminase; Point Mutation; RNA; RNA Editing
PubMed: 30814692
DOI: 10.1038/s41592-019-0332-z -
Analytical and Bioanalytical Chemistry Mar 2023Cancer is a genetic disease induced by mutations in DNA, in particular point mutations in important driver genes that lead to protein malfunctioning and ultimately to... (Review)
Review
Cancer is a genetic disease induced by mutations in DNA, in particular point mutations in important driver genes that lead to protein malfunctioning and ultimately to tumorigenesis. Screening for the most common DNA point mutations, especially in such genes as TP53, BRCA1 and BRCA2, EGFR, KRAS, or BRAF, is crucial to determine predisposition risk for cancer or to predict response to therapy. In this review, we briefly depict how these genes are involved in cancer, followed by a description of the most common techniques routinely applied for their analysis, including high-throughput next-generation sequencing technology and less expensive low-throughput options, such as real-time PCR, restriction fragment length polymorphism, or high resolution melting analysis. We then introduce benefits of electrochemical biosensors as interesting alternatives to the standard methods in terms of cost, speed, and simplicity. We describe most common strategies involved in electrochemical biosensing of point mutations, relying mostly on PCR or isothermal amplification techniques, and critically discuss major challenges and obstacles that, until now, prevented their more widespread application in clinical settings.
Topics: Humans; Point Mutation; Mutation; Neoplasms; DNA; Biosensing Techniques; High-Throughput Nucleotide Sequencing; Genetic Predisposition to Disease
PubMed: 36289102
DOI: 10.1007/s00216-022-04388-7 -
Cell Mar 2020Sickle cell disease (SCD) is caused by a point mutation in the β-globin gene that creates hemoglobin S (HbS). Upon deoxygenation, HbS forms long polymers that distort...
Sickle cell disease (SCD) is caused by a point mutation in the β-globin gene that creates hemoglobin S (HbS). Upon deoxygenation, HbS forms long polymers that distort the shape of red blood cells, causing hemolysis and vaso-occlusion. Voxelotor inhibits HbS polymerization, the root cause of SCD complications. To view this Bench to Bedside, open or download the PDF.
Topics: Anemia, Sickle Cell; Benzaldehydes; Hemoglobin, Sickle; Humans; Point Mutation; Polymerization; Pyrazines; Pyrazoles; beta-Globins
PubMed: 32142671
DOI: 10.1016/j.cell.2020.01.019 -
BMC Evolutionary Biology Jul 2020Tumors are widely recognized to progress through clonal evolution by sequentially acquiring selectively advantageous genetic alterations that significantly contribute to...
BACKGROUND
Tumors are widely recognized to progress through clonal evolution by sequentially acquiring selectively advantageous genetic alterations that significantly contribute to tumorigenesis and thus are termned drivers. Some cancer drivers, such as TP53 point mutation or EGFR copy number gain, provide exceptional fitness gains, which, in time, can be sufficient to trigger the onset of cancer with little or no contribution from additional genetic alterations. These key alterations are called superdrivers.
RESULTS
In this study, we employ a Wright-Fisher model to study the interplay between drivers and superdrivers in tumor progression. We demonstrate that the resulting evolutionary dynamics follow global clonal expansions of superdrivers with periodic clonal expansions of drivers. We find that the waiting time to the accumulation of a set of superdrivers and drivers in the tumor cell population can be approximated by the sum of the individual waiting times.
CONCLUSIONS
Our results suggest that superdriver dynamics dominate over driver dynamics in tumorigenesis. Furthermore, our model allows studying the interplay between superdriver and driver mutations both empirically and theoretically.
Topics: Biological Evolution; Clonal Evolution; Disease Progression; Humans; Mutation; Neoplasms; Point Mutation; Time Factors
PubMed: 32689942
DOI: 10.1186/s12862-020-01647-y -
BMC Bioinformatics Oct 2022RNA deleterious point mutation prediction was previously addressed with programs such as RNAmute and MultiRNAmute. The purpose of these programs is to predict a global...
BACKGROUND
RNA deleterious point mutation prediction was previously addressed with programs such as RNAmute and MultiRNAmute. The purpose of these programs is to predict a global conformational rearrangement of the secondary structure of a functional RNA molecule, thereby disrupting its function. RNAmute was designed to deal with only single point mutations in a brute force manner, while in MultiRNAmute an efficient approach to deal with multiple point mutations was developed. The approach used in MultiRNAmute is based on the stabilization of the suboptimal RNA folding prediction solutions and/or destabilization of the optimal folding prediction solution of the wild type RNA molecule. The MultiRNAmute algorithm is significantly more efficient than the brute force approach in RNAmute, but in the case of long sequences and large m-point mutation sets the MultiRNAmute becomes exponential in examining all possible stabilizing and destabilizing mutations.
RESULTS
An inherent limitation in the RNAmute and MultiRNAmute programs is their ability to predict only substitution mutations, as these programs were not designed to work with deletion or insertion mutations. To address this limitation we herein develop a very fast algorithm, based on suboptimal folding solutions, to predict a predefined number of multiple point deleterious mutations as specified by the user. Depending on the user's choice, each such set of mutations may contain combinations of deletions, insertions and substitution mutations. Additionally, we prove the hardness of predicting the most deleterious set of point mutations in structural RNAs.
CONCLUSIONS
We developed a method that extends our previous MultiRNAmute method to predict insertion and deletion mutations in addition to substitutions. The additional advantage of the new method is its efficiency to find a predefined number of deleterious mutations. Our new method may be exploited by biologists and virologists prior to site-directed mutagenesis experiments, which involve indel mutations along with substitutions. For example, our method may help to investigate the change of function in an RNA virus via mutations that disrupt important motifs in its secondary structure.
Topics: INDEL Mutation; Mutation; Point Mutation; RNA; Sequence Analysis, RNA
PubMed: 36241988
DOI: 10.1186/s12859-022-04943-0 -
Frontiers in Immunology 2022Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell...
Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa. A significantly reduced population of CD4 T cells was observed in mice obtained from the long-term homozygous breeding of (Map1, ) knockout mice; this phenotype was not attributed to the original knocked-out gene. MHC II expression was generally reduced, together with a marked deficiency of H2-Aa in the immune cells of these mice. Using cDNA and DNA sequencing, a spontaneous H2-Aa point mutation that led to false pre-mRNA splicing, deletion of eight bases in the mRNA, and protein frameshift was identified in these mice. These findings led to the discovery of a new type of spontaneous MHC II deficiency and provided a new paradigm to explain type II BLS in mice.
Topics: Animals; CD4-Positive T-Lymphocytes; Histocompatibility Antigens Class II; Mice; Mice, Knockout; Point Mutation; Severe Combined Immunodeficiency; T-Lymphocytes
PubMed: 35309308
DOI: 10.3389/fimmu.2022.810824 -
Activity and Point Mutation G699V in PcoORP1 Confer Resistance to Oxathiapiprolin in Field Isolates.Journal of Agricultural and Food... Nov 2022The oxysterol-binding protein inhibitor oxathiapiprolin is a new fungicide for controlling oomycetes diseases. Besides, laboratory mutagenesis oxathiapiprolin-resistance...
The oxysterol-binding protein inhibitor oxathiapiprolin is a new fungicide for controlling oomycetes diseases. Besides, laboratory mutagenesis oxathiapiprolin-resistance among phytopathogenic oomycetes in the field remains unknown. Here, the sensitivity of 97 isolates to oxathiapiprolin was examined that were collected between 2011 and 2016. We obtained a baseline sensitivity with a mean EC value of 5.2639 × 10 μg mL. We showed that 6/32 isolates collected in Fujian Province from 2019 to 2020 were resistant to oxathiapiprolin without a significant fitness penalty on sporulation, vegetative growth, and virulence of the field isolates. The oxathiapiprolin resistance field isolates contained the point mutation glycine to valine at 699 in . The point mutation G699V was verified to confer resistance of to oxathiapiprolin using the CRISPR/Cas9 system. The mutation G699V decreased the binding affinity between oxathiapiprolin and . These results will improve our understanding of the mechanism of resistance to oxathiapiprolin under field conditions.
Topics: Phytophthora; Point Mutation; Plant Diseases; Hydrocarbons, Fluorinated; Fungicides, Industrial
PubMed: 36315898
DOI: 10.1021/acs.jafc.2c06707 -
Methods in Cell Biology 2020The maternally inherited mitochondrial DNA (mtDNA) is a circular 16,569bp double stranded DNA that encodes 37 genes, 24 of which (2 rRNAs and 22 tRNAs) are necessary for...
The maternally inherited mitochondrial DNA (mtDNA) is a circular 16,569bp double stranded DNA that encodes 37 genes, 24 of which (2 rRNAs and 22 tRNAs) are necessary for transcription and translation of 13 polypeptides that are all subunits of respiratory chain. Pathogenic mutations in mtDNA cause respiratory chain dysfunction, and are the underlying defect in an ever-increasing number of mtDNA-related encephalomyopathies with distinct phenotypes. In this chapter, we present an overview of mtDNA mutations and describe the molecular techniques currently employed in our laboratory to detect two types of mtDNA mutations: single-large-scale rearrangements and point mutations.
Topics: DNA Mutational Analysis; DNA, Mitochondrial; Gene Rearrangement; Genome, Mitochondrial; High-Throughput Nucleotide Sequencing; Humans; Mutation; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length
PubMed: 32183969
DOI: 10.1016/bs.mcb.2019.11.009