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Two-step model of successive inversions to produce an inversion of one DNA segment (B to B′) and a concomitant translocation of an adjoining DNA segment (C). Two alternative pathways, which differ in the order of the larger and smaller inversions, are proposed: the green path begins with a large inversion, and the red path ends with a large inversion. In both pathways, segment C is inverted in the first step, and it is proposed that there was positive selective pressure favoring a subsequent cell population in which segment C is restored to its original orientation after the second step.
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In the present study, the chromosomes of two members of the Thermotogales were compared. A whole-genome alignment of Thermotoga maritima MSB8 and Thermotoga neapolitana NS-E has revealed numerous large-scale DNA rearrangements, most of which are associated with CRISPR DNA repeats and/or tRNA
genes. These DNA rearrangements do not include the putati...
Citations
... The horizontal gene transfer (HGTs) mechanisms seen in prokaryotes further complicate their locus structure. The CRISPR repeat sequences have also been shown to favor homologous recombination (HR) and cause genomic rearrangements (DeBoy et al., 2006). To have a comprehensive classification for such a dynamic and evolving system is tedious. ...
... The CRISPR locus appears to have additional activities in various systems, in addition to its protective roles. The repeats in their natural form boons a prospect for homology-driven genome rearrangements (DeBoy et al., 2006). In vitro, the Cas1 protein from E. coli demonstrated nuclease activity against single-stranded and branched DNAs from Holliday Junctions and replication forks. ...
... Chromosomal rearrangements are not unusual for this group and have also been reported in other Thermotogales species. Chromosomal rearrangements have been suggested to affect species evolution [47,48]. ...
Fervidobacterium pennivorans subsp. keratinolyticus subsp. nov. strain T was isolated from a terrestrial, high-altitude hot spring in Tajikistan. This strain is an obligate anaerobic rod and their cells occur singly, in pairs, or as short chains under the optimal growth conditions of a temperature of 65 °C and pH 6.5, with peptone, glucose, and galactose as the preferred substrates. The minimum generation time of this strain is 150 min. Strain T can efficiently degrade feather keratin at 65–75 °C; this unusual feature is also exhibited by a few other members of the Fervidobacterium genus. The total genome size of this bacterial strain is 2,002,515 base pairs, with a C + G content of 39.0%. The maximum digital DNA–DNA hybridization (dDDH) value of 76.9% was observed on comparing the genome of this strain with that of Fervidobacterium pennivorans type strain DSM9078. This study describes the physiological and genomic properties of strain T, with an emphasis on its keratinolytic power and differences from other members of the genus Fervidobacterium.
... The introduction of the CRISPR/Cas9 method as a genome-editing technique [14,15] represented an important step in the advancement of the genome-editing method thanks to the ease and effectiveness of use as well as the great adaptability to different biomedical areas. CRISPR/Cas9 systems are implemented through adaptive immune mechanisms capable of correcting intrinsic errors in the DNA that are the basis of various diseases. ...
Genomic editing technology has been developed since 2010 through the use of some techniques, such as the clustered regularly interspaced short palindromic repeat (CRISPR) DNA sequences/CRISPR-associated (Cas) type-9 method, or through genetic manipulation tools derived from host response systems from some microbes (e.g., bacteria) against plasmids and viruses. The introduction of the CRISPR/Cas9 method as a genome-editing instrument represented an important step in the advancement of the genome-editing method thanks to the ease and effectiveness of use as well as the great adaptability to different biomedical areas. This paragraph will discuss all conceived technologies and new perspectives that can be applied in treating some associated genetic disorders, such as cardiovascular diseases, metabolic diseases, inflammatory diseases, and tumors by means of reversible and modulating control of gene expression epigenetics using genetic editing techniques.KeywordsCRISPR/Cas9Genome editingCardiovascular diseasesMetabolic diseasesOral diseasesInflammatory diseasesCancerEpigenetic
... CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) was first identified in Escherichia Coli in 1987 as a group of repeated fragments comprised of 29 nucleotides that are separated by fragments of 32 nucleotides of unique varied sequence [1]. This was shown to play a role in multiple cellular processes including thermal adaptation [15], DNA repair [4] and chromosomal rearrangements [16]. In addition, a comparable 24 to 40 nucleotide short palindromic repeat sequence interspaced by a 20 to 58 varied nucleotide sequence was later identified in multiple species of bacteria and archaea, such as in Streptococcus Hormone-receptor and HER2 positive cancer subtypes have proven to be responsive to drugs that either have a direct effect on hormone receptors or HER2 or the pathways involved in hormonal disturbances. ...
... CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) was first identified in Escherichia Coli in 1987 as a group of repeated fragments comprised of 29 nucleotides that are separated by fragments of 32 nucleotides of unique varied sequence [1]. This was shown to play a role in multiple cellular processes including thermal adaptation [15], DNA repair [4] and chromosomal rearrangements [16]. In addition, a comparable 24 to 40 nucleotide short palindromic repeat sequence interspaced by a 20 to 58 varied nucleotide sequence was later identified in multiple species of bacteria and archaea, such as in Streptococcus pyogenes [17,18]. ...
Breast cancer is one of the most prevalent forms of cancer globally and is among the leading causes of death in women. Its heterogenic nature is a result of the involvement of numerous aberrant genes that contribute to the multi-step pathway of tumorigenesis. Despite the fact that several disease-causing mutations have been identified, therapy is often aimed at alleviating symptoms rather than rectifying the mutation in the DNA sequence. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 is a groundbreaking tool that is being utilized for the identification and validation of genomic targets bearing tumorigenic potential. CRISPR/Cas9 supersedes its gene-editing predecessors through its unparalleled simplicity, efficiency and affordability. In this review, we provide an overview of the CRISPR/Cas9 mechanism and discuss genes that were edited using this system for the treatment of breast cancer. In addition, we shed light on the delivery methods—both viral and non-viral—that may be used to deliver the system and the barriers associated with each. Overall, the present review provides new insights into the potential therapeutic applications of CRISPR/Cas9 for the advancement of breast cancer treatment.
... In fact, several studies show that spacers can derive from the host chromosome [88][89][90] , causing autoimmunity and cell death [91][92][93] . On the other hand, selftargeting can also drive genome evolution, which potentially increases fitness [94][95][96] . The acquisition rate of genome-derived spacers is desirably low in order to avoid auto-immunity and bacteria have developed different strategies to bias acquisition towards invading elements. ...
Prokaryoten haben eine Vielzahl verschiedener Mechanismen entwickelt um sich vor Bedrohungen wie Bakteriophagen zu schützen. CRISPR-Cas (clustered regularly interspaced palindromic repeats – CRISPR-associated genes) Systeme stellen die bislang einzigen adaptiven Immunsysteme von Bakterien und Archaeen dar. Die Proteine Cas1 und Cas2 ermöglichen die adaptive Abwehr, indem sie einen Komplex bilden, der kurze Fragmente (Spacer) invasiver DNS in den chromosomalen CRISPR Lokus integriert. Dieser Prozess ist bekannt als CRISPR adaptation. Im Falle einer Infektion durch gleiche oder verwandte Bakteriophagen werden die Spacer Sequenzen zu kurzen RNS Molekülen transkribiert und ermöglichen es Cas Nukleasen komplementäre Sequenzen zu binden und zu zerstören. Zahlreiche Studien zeigen die biochemischen Mechanismen, die im Adaptionsprozess involviert sind. Unser Wissen ist jedoch nur auf wenige Subtypen beschränkt und die stetige Entdeckung neuer CRISPR-Cas Systeme zeigt spezifische Variationen im Adaptionsprozess auf. Diese Studie untersucht die Adaptionsprozesse des Subtyps V-A. Mittels verschiedener biochemischer Analysen beschreiben wir die Funktion der Untereinheit Cas2 und zeigen, dass das aktive Zentrum des Proteins eine wichtige Rolle während der Integration neuer Spacer einnimmt und damit anders als homologe Cas1-Cas2 Komplexe agiert. Wir beschreiben einen Mechanismus, indem das aktive Zentrum von Cas2 divalente Metallionen bindet, welche die Interaktion des Komplexes zum Spacer unterstützt und die Vollendung der Integrationsreaktion ermöglicht. Type V-A Systeme kodieren außerdem für die Proteine Cas4 und Cas12a. Wir zeigen, dass Cas4 die Auswahl der Spacer Sequenzen beeinflusst, die von Cas1-Cas2 in den CRISPR Lokus integriert werden. Die Rolle von Cas12a bedarf weiterer Untersuchungen, aber die hier vorgestellten Ergebnisse demonstrieren, dass die Endonuklease-Aktivität des Proteins entscheidend für die Aufnahme neuer Spacer ist.
... The origin of CRISPR/Cas9 CRISPR was first found in Escherichia coli by Ishino et al. [7]. After that, several studies found CRISPRs could participate in lots of cellular processes, such as replicon partitioning [8], thermal adaptation [9], DNA repair [10] and chromosomal rearrangements [11]. Since then, CRISPRs have been identified as a defense mechanism to cleave invading nucleic acid in bacteria and archaic [12]. ...
The recent developments of clustered regularly interspaced short palindromic repeats(CRISPR)/-associate protein 9 (CRISPR/Cas9) have got scientific interests due to the straightforward, efficient and versatile talents of it. Furthermore, the CRISPR/Cas9 system has democratized access to gene editing in many biological fields, including cancer. Cancer development is a multistep process caused by innate and acquired mutations and leads to the initiation and progression of tumorigenesis. It is obvious that establishing appropriate animal cancer models which can simulate human cancers is crucial for cancer research currently. Since the emergence of CRISPR/Cas9, considerable efforts have been taken by researchers to apply this technology in generating animal cancer models. Although there is still a long way to go we are happy to see the achievements we have made and the promising future we have.
... The variation in spacer elements have been reported for five strains of Thermotoga neapolitana [41,50]. A Type III Csm complex (TthCsm) system active at 65 C has been identified from Thermus thermophiles [80]. ...
... actinobacterium Streptomyces kanamiceticus and E. coli. Several groundbreaking findings were made which includes close similarities between sequences and spacers present within non-CRISPR loci of several viral, bacterial DNAs, sorting of Cas protein families, an adaptive defence system composed of CRISPR arrays that provides specific immunity against invading genetic elements to viral infection byloss of older spacers and acquisition of newer spacers, delineation of the tracrRNA based type II processing mechanism that consolidated the concept of CRISPR/Cas system [16][17][18][19][20][21][22][23]. [51]. ...
The preexisting prokaryotic defense system i.e. CRISPR-Cas9 system and the story behind the most successful biological genome editing tool among the eukaryotic systems is a curious topic of interest for the researchers. How this genome editing tool creates a hallmark in the treatment of various diseases and improves medical science research with the genetic engineering is also a part of our discussion. This review article summarizes the CRISPR-Cas9 system in living systems, the molecular mechanism along with its applications on different systems. We believe an illustrative enigmaof this tool will be helpful for the scientific community to overcome the questionnaires behind the execution of this technique.
... This system is found in approximately 50% of the bacterial genomes that are sequenced and in 87% of the genomes of archaea (9)(10)(11)(12). It is also important in a range of additional functions, including replicon divisions (13), high-temperature adaptation (14), chromosomal rearrangements (15) and DNA repair (16). ...
Genome editing reemerged in 2012 with the development of CRISPR/Cas9 technology, which is a genetic manipulation tool derived from the defense system of certain bacteria against viruses and plasmids. This method is easy to apply and has been used in a wide variety of experimental models, including cell lines, laboratory animals, plants, and even in human clinical trials. The CRISPR/Cas9 system consists of directing the Cas9 nuclease to create a site‑directed double‑strand DNA break using a small RNA molecule as a guide. A process that allows a permanent modification of the genomic target sequence can repair the damage caused to DNA. In the present study, the basic principles of the CRISPR/Cas9 system are reviewed, as well as the strategies and modifications of the enzyme Cas9 to eliminate the off‑target cuts, and the different applications of CRISPR/Cas9 as a system for visualization and gene expression activation or suppression. In addition, the review emphasizes on the potential application of this system in the treatment of different diseases, such as pulmonary, gastrointestinal, hematologic, immune system, viral, autoimmune and inflammatory diseases, and cancer.
... As such, gene inversion events are an optimal means by which the cellular conflict burden could be reduced over evolutionary time. At least two methods for identifying inverted genes/fragments are available: fully assembled genome comparison between strains of the same species, and GC skew analysis [21][22][23][24] . Though whole-genome comparison is highly accurate, it is low throughput and requires the computationally intensive comparison of specific genomes [25][26][27] . ...
Most bacterial genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This bias reduces the frequency of detrimental head-on collisions between the two machineries. The negative outcomes of these collisions should lead to selection against head-on alleles, maximizing genome co-orientation. Our findings challenge this model. Using the GC skew calculation, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. Against expectations, we find that a large number of co-oriented genes have inverted to the head-on orientation, presumably increasing the frequency of head-on replication-transcription conflicts. Furthermore, we find that head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of non-synonymous mutations and are more frequently under positive selection (dN/dS > 1). Based on these results, we propose that spontaneous gene inversions can increase the evolvability and pathogenic capacity of bacteria through head-on replication-transcription collisions.
