scholarly journals A chimeric nuclease substitutes CRISPR-Cas: A phage weaponizes laterally acquired specificity to destroy subviral parasites

2021 ◽  
Author(s):  
Zachary K. Barth ◽  
Maria H.T. Nguyen ◽  
Kimberley D. Seed
Keyword(s):  
Replication Origin ◽  
Selective Pressure ◽  
Mobile Element ◽  
Dna Binding Domain ◽  
Evolutionary Forces ◽  
Defense Systems ◽  
Genome Defense ◽  
Temporal Succession ◽  
Cas A ◽  
Replication Module

AbstractMobile genetic elements, elements that can move horizontally between genomes, have profound effects on their hosts fitness. The PLE is a mobile element that integrates into the chromosome of Vibrio cholerae and parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA binding domain that is highly similar to some PLE replication origin binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.

scholarly journals A chimeric nuclease substitutes a phage CRISPR-Cas system to provide sequence-specific immunity against subviral parasites

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Zachary K Barth ◽  
Maria HT Nguyen ◽  
Kimberley D Seed
Keyword(s):  
Replication Origin ◽  
Selective Pressure ◽  
Mobile Element ◽  
Dna Binding Domain ◽  
Evolutionary Forces ◽  
Defense Systems ◽  
Origins Of Replication ◽  
Genome Defense ◽  
Temporal Succession ◽  
Replication Module

Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their host's fitness. The phage-inducible chromosomal island-like element (PLE) is a mobile element that integrates into the chromosome of Vibrio cholerae and parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here, we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA-binding domain that is highly similar to some PLE replication origin-binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.

scholarly journals The Specificity of TRIM5α-Mediated Restriction Is Influenced by Its Coiled-Coil Domain

2010 ◽  
Vol 84 (11) ◽  
pp. 5790-5801 ◽  
Author(s):  
Pierre V. Maillard ◽  
Gabriela Ecco ◽  
Millán Ortiz ◽  
Didier Trono
Keyword(s):  
New World ◽  
Selective Pressure ◽  
Coiled Coil ◽  
Genome Integrity ◽  
New World Monkeys ◽  
Restriction Factors ◽  
Evolutionary Forces ◽  
Coiled Coil Domain ◽  
Functional Analyses ◽  
Antiretroviral Activity

ABSTRACT Retroviruses are both powerful evolutionary forces and dangerous threats to genome integrity. As such, they have imposed strong selective pressure on their hosts, notably triggering the emergence of restriction factors, such as TRIM5α, that act as potent barriers to their cross-species transmission. TRIM5α orthologues from different primates have distinct retroviral restriction patterns, largely dictated by the sequence of their C-terminal PRYSPRY domain, which binds the capsid protein of incoming virions. Here, by combining genetic and functional analyses of human and squirrel monkey TRIM5α, we demonstrate that the coiled-coil domain of this protein, thus far essentially known for mediating oligomerization, also conditions the spectrum of antiretroviral activity. Furthermore, we identify three coiled-coil residues responsible for this effect, one of which has been under positive selection during primate evolution, notably in New World monkeys. These results indicate that the PRYSPRY and coiled-coil domains cooperate to determine the specificity of TRIM5α-mediated capture of retroviral capsids, shedding new light on this complex event.

scholarly journals The Use of GC-, Codon-, and Amino Acid-frequencies to Understand the Evolutionary Forces at a Genomic Scale

2019 ◽  
Author(s):  
Arne Elofsson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Selective Pressure ◽  
Amino Acid Level ◽  
Gc Content ◽  
Frequency Variation ◽  
Evolutionary Forces ◽  
Charged Amino Acids ◽  
Plausible Model ◽  
Selective Forces

1AbstractIt is well known that the GC content varies enormously between organisms; this is believed to be caused by a combination of mutational preferences and selective pressure. Within coding regions, the variation of GC is more substantial in position three and smaller in position one and two. Less well known is that this variation also has an enormous impact on the frequency of amino acids as their codons vary in GC content. For instance, the fraction of alanines in different proteomes varies from 1.1% to 16.5%. In general, the frequency of different amino acids correlates strongly with the number of codons, the GC content of these codons and the genomic GC contents. However, there are clear and systematic deviations from the expected frequencies. Some amino acids are more frequent than expected by chance, while others are less frequent. A plausible model to explain this is that there exist two different selective forces acting on the genes; First, there exists a force acting to maintain the overall GC level and secondly there exists a selective force acting on the amino acid level. Here, we use the divergence in amino acid frequency from what is expected by the GC content to analyze the selective pressure acting on codon frequencies in the three kingdoms of life. We find four major selective forces; First, the frequency of serine is lower than expected in all genomes, but most in prokaryotes. Secondly, there exist a selective pressure acting to balance positively and negatively charged amino acids, which results in a reduction of arginine and negatively charged amino acids. This results in a reduction of arginine and all the negatively charged amino acids. Thirdly, the frequency of the hydrophobic residues encoded by a T in the second codon position does not change with GC. Their frequency is lower in eukaryotes than in prokaryotes. Finally, some amino acids with unique properties, such as proline glycine and proline, are limited in their frequency variation.

scholarly journals A quantitative model for characterizing the evolutionary history of mammalian gene expression

2017 ◽  
Author(s):  
Jenny Chen ◽  
Ross Swofford ◽  
Jeremy Johnson ◽  
Beryl B. Cummings ◽  
Noga Rogel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Evolutionary History ◽  
Selective Pressure ◽  
Mammalian Species ◽  
Quantitative Model ◽  
Process Models ◽  
Stabilizing Selection ◽  
Expression Data ◽  
Evolutionary Forces ◽  
History Of

AbstractCharacterizing the evolutionary history of a gene’s expression profile is a critical component for understanding the relationship between genotype, expression, and phenotype. However, it is not well-established how best to distinguish the different evolutionary forces acting on gene expression. Here, we use RNA-seq across 7 tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein-Uhlenbeck (OU) process. This stochastic process models expression trajectories across time as Gaussian distributions whose variance is parameterized by the rate of genetic drift and strength of stabilizing selection. We use these mathematical properties to identify expression pathways under neutral, stabilizing, and directional selection, and quantify the extent of selective pressure on a gene’s expression. We further detect deleterious expression levels outside expected evolutionary distributions in expression data from individual patients. Our work provides a statistical framework for interpreting expression data across species and in disease.One Sentence SummaryWe demonstrate the power of a stochastic model for quantifying selective pressure on expression and estimating evolutionary distributions of optimal gene expression.

NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

1999 ◽  
Vol 96 (9/10) ◽  
pp. 1580-1584 ◽  
Author(s):  
I. Ségalas ◽  
S. Desjardins ◽  
H. Oulyadi ◽  
Y. Prigent ◽  
S. Tribouillard ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Peptide Fragments ◽  
Nmr Studies ◽  
Related Peptide

Study of Alnus incana L. Moench fruit extract biologically active substances influence on resistance development in mls-resistant staphylococci skin isolates

2018 ◽  
Vol 22 (2) ◽  
pp. 263-266
Author(s):  
R.V. Kutsyk ◽  
O.I. Yurchyshyn
Keyword(s):  
Selective Pressure ◽  
Biological Response ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Alnus Incana ◽  
Fruit Extract ◽  
Antimicrobial Drugs ◽  
Resistance Development ◽  
Subinhibitory Concentrations ◽  
Active Substances

The emergence of microorganisms resistant strains is a natural biological response to the use of antimicrobial drugs that creates selective pressure, contributing to pathogens selection, survival and reproduction. The purpose of the investigation was to study the resistance development of staphylococci skin isolates to erythromycin and influence on it Alnus incana L. fruit extract subinhibitory concentrations. Development of resistance to erythromycin and influence on it Alnus incana L. fruit extract (extraction by 90% ethanol) subinhibitory concentrations were conducted with S epidermidis strains: sensitive and resistant to 14 and 15-membered macrolides. The study was carried out within 30 days by multiple consecutive passages of staphylococci test strains (concentration 1×107 CFU/ml) into test tubes containing broth and erythromycin ranging from 3 doubling dilutions above to doubling dilutions below the minimum inhibitory concentration. Statistical analysis of the results was carried out by one-and two-factor analysis of variance (ANOVA) and Microsoft Office Excel 2011. Rapid increase of resistance from 32 to 1024 μg/ml (F=34.2804; F> Fstand. max = 5.9874; p=0.0011) for S.epidermidis with a low level of resistance to 14 and 15-membered macrolides resistance to the erythromycine was observed. In the presence of Alnus incana L. fruit extract subinhibitory concentrations (¼ MIC), the initial MIC of erythromycin was decreased by 32 times to 1 μg/ml (F = 9.7497; F> Fstand. max = 5.9874; p = 0.0205). The sensitive strain after 30 passages did not develop resistance to erythromycin. Under the influence of erythromycin selective pressure, S.epidermidis strain with low initial level of MLS-resistance rapidly reaches a high-level resistance. Biologically active substances of the Alnus incana L. fruit extract significantly inhibit the resistance development in S. epidermidis to macrolides and eliminate it phenotypic features.

Les ostéomes ostéoïdes du pied et de la cheville : à propos d’une série de 17 cas à 93 mois de recul moyen

2020 ◽  
Vol 36 (3) ◽  
pp. 65-74
Author(s):  
K. Soudy ◽  
T. Amouyel ◽  
C. Szymanski ◽  
C. Maynou
Keyword(s):  
Sf 36 ◽  
Cas A ◽  
Photocoagulation Laser ◽  
Tumeurs Osseuses ◽  
Étude Rétrospective

L’ostéome ostéoïde (OO) représente 10 à 12 % des tumeurs osseuses bénignes. Le pied et la cheville sont concernés dans 2 à 15 % des cas. La résection chirurgicale à ciel ouvert est maintenant supplantée par les techniques percutanées guidées par le scanner qu’il s’agisse de la thermocoagulation par radiofréquence, de la photocoagulation laser ou de la cryoablation. Cette étude a pour but d’évaluer l’efficacité thérapeutique de la thermocoagulation scanoguidée (TPS). Il s’agit d’une étude rétrospective monocentrique incluant tous les OO traités par TPS au CHRU de Lille entre 2003 et 2015, ayant un recul minimum d’un an. Dix-sept patients ont été inclus, dix hommes et sept femmes, d’âge moyen 24 ans. Quinze patients ont fait l’objet d’une évaluation par questionnaire téléphonique au recul moyen de 93 mois. Les douleurs ont disparu dans un délai moyen de 4,5 jours. La reprise du travail se faisait en 11 jours en moyenne. Le degré de satisfaction moyen est de 92 %, le score SF-36 de 93, le score FAAM de 177. Une seule récidive est à signaler, mais aucune complication cutanée ou vasculonerveuse. Le traitement des OO localisés au pied et à la cheville par TPS permet d’excellents résultats sans morbidité.

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