A giant virus , sometimes referred to as a girus , is a very large virus , some of which are larger than typical bacteria. All known giant viruses belong to the phylum Nucleocytoviricota .
51-401: Mimivirus is a genus of giant viruses , in the family Mimiviridae . Amoeba serve as their natural hosts. This genus contains a single identified species named Acanthamoeba polyphaga mimivirus (APMV). It also refers to a group of phylogenetically related large viruses. In colloquial speech, APMV is more commonly referred to as just "mimivirus". Mimivirus, short for "mimicking microbe",
102-483: A ribosome can transfer the amino acid from the tRNA onto a growing peptide , according to the genetic code. Aminoacyl tRNA therefore plays an important role in RNA translation , the expression of genes to create proteins. The synthetase first binds ATP and the corresponding amino acid (or its precursor ) to form an aminoacyl-adenylate, releasing inorganic pyrophosphate (PPi). The adenylate-aaRS complex then binds
153-674: A bacterium on Gram staining . The same team that discovered the mimivirus later discovered a slightly larger virus, dubbed the mamavirus , and the Sputnik virophage that infects it. Mimivirus has been placed into a viral family by the International Committee on Taxonomy of Viruses as a member of the Mimiviridae , and has been placed into Group I of the Baltimore classification system. Although not strictly
204-564: A capsid protein and a TFII-like transcription factor were found. However, three distinct aminoacyl tRNA synthetase enzyme transcripts and four unknown mRNA molecules specific to mimivirus were also found. These pre-packaged transcripts can be translated without viral gene expression and are likely to be necessary to Mimivirus for replication. Other DNA viruses , such as the Human cytomegalovirus and Herpes simplex virus type-1 , also feature pre-packaged mRNA transcripts. The mimivirus genome
255-548: A domain with the sole purpose of editing, they make up for it by having specific binding and activation of their affiliated amino acids. Another contribution to the accuracy of these synthetases is the ratio of concentrations of aminoacyl-tRNA synthetase and its cognate tRNA. Since tRNA synthetase improperly acylates the tRNA when the synthetase is overproduced, a limit must exist on the levels of aaRSs and tRNAs in vivo. There are two classes of aminoacyl tRNA synthetase, each composed of ten enzymes: The amino acids are attached to
306-610: A given specificity are evolutionarily closer to one another than to aaRSs of another specificity. However, AsnRS and GlnRS group within AspRS and GluRS, respectively. Most of the aaRSs of a given specificity also belong to a single class. However, there are two distinct versions of the LysRS - one belonging to the class I family and the other belonging to the class II family. The molecular phylogenies of aaRSs are often not consistent with accepted organismal phylogenies . That is, they violate
357-424: A kind of collagen ). In addition, mimivirus has genes coding for nucleotide and amino acid synthesis, which even some small obligate intracellular bacteria lack. They do, however, lack any genes for ribosomal proteins, making mimivirus dependent on a host cell for protein translation and energy metabolism. Because its lineage is very old and could have emerged prior to cellular organisms, Mimivirus has added to
408-419: A method of classification, mimivirus joins a group of large viruses known as nucleocytoplasmic large DNA viruses (NCLDV). They are all large viruses which share both molecular characteristics and large genomes. The mimivirus genome also possesses 21 genes encoding homologs to proteins which are seen to be highly conserved in the majority of NCLDVs, and further work suggests that mimivirus is an early divergent of
459-512: A mimivirus has been isolated from a Tunisian woman suffering from pneumonia. There is evidence that mimivirus can infect macrophages . Mimivirus shows many characteristics which place it at the boundary between living and non-living. It is as large as several bacterial species, such as Rickettsia conorii and Tropheryma whipplei , possesses a genomic size comparable to that of several bacteria, including those above, and codes for products previously not thought to be encoded by viruses (including
510-468: A pair of arginine residues to establish salt bridges to its ATP ligand. This oppositional implementation is manifested in two structural motifs, the Backbone Brackets and Arginine Tweezers, which are observable in all class I and class II structures, respectively. The high structural conservation of these motifs suggest that they must have been present since ancient times. Most of the aaRSs of
561-535: A previously unrecognized layer of biology: these proteins control gene expression within the cell of origin, and when released exert homeostatic and developmental control in specific human cell types, tissues and organs during adult or fetal development or both, including pathways associated with angiogenesis , inflammation , the immune response , the mechanistic target of rapamycin (mTOR) signalling, apoptosis , tumorigenesis , and interferon gamma (IFN- γ ) and p53 signalling. In 2022, it
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#1732775286918612-666: A typical scenario, an aaRS consists of a catalytic domain (where both the above reactions take place) and an anticodon binding domain (which interacts mostly with the anticodon region of the tRNA). Transfer-RNAs for different amino acids differ not only in their anticodon but also at other points, giving them slightly different overall configurations. The aminoacyl-tRNA synthetases recognize the correct tRNAs primarily through their overall configuration, not just through their anticodon. In addition, some aaRSs have additional RNA binding domains and editing domains that cleave incorrectly paired aminoacyl-tRNA molecules. The catalytic domains of all
663-507: Is a disturbance of dimer shape/formation which has a direct relationship with its function. These correlations between aaRSs and certain diseases have opened up a new door to synthesizing therapeutics. The novel domain additions to aaRS genes are accretive and progressive up the Tree of Life . The strong evolutionary pressure for these small non-catalytic protein domains suggested their importance. Findings beginning in 1999 and later revealed
714-491: Is a linear, double-stranded molecule of DNA with 1,181,404 base pairs in length. This makes it one of the largest viral genomes known, outstripping the next-largest virus genome of the Cafeteria roenbergensis virus by about 450,000 base pairs. In addition, it is larger than at least 30 cellular clades . In addition to the large size of the genome, mimivirus possesses an estimated 979 protein-coding genes , far exceeding
765-648: Is also a topic of debate: by one proposal, it might represent a fourth domain of life, but this has been largely discounted. The whole list is in the Giant Virus Toplist created by the Giant Virus Finder software. As of June 11, 2018, there were 183 listed. Mutator S (MutS) and its homologs are a family of DNA mismatch repair proteins involved in the mismatch repair system that acts to correct point mutations or small insertion/deletion loops produced during DNA replication, increasing
816-425: Is caused by a heritable mutation in glycol-tRNA and tyrosyl-tRNA. Diabetes, a metabolic disease, induces oxidative stress, which triggers a build up of mitochondrial tRNA mutations. It has also been discovered that tRNA synthetases may be partially involved in the etiology of cancer. A high level of expression or modification of aaRSs has been observed within a range of cancers. A common outcome from mutations of aaRSs
867-405: Is conserved from that point on. As genetic efficiency evolved in higher organisms, 13 new domains with no obvious association with the catalytic activity of aaRSs genes have been added. In some of the aminoacyl tRNA synthetases, the cavity that holds the amino acid can be mutated and modified to carry unnatural amino acids synthesized in the lab, and to attach them to specific tRNAs. This expands
918-431: Is introducing amino acids bearing reactive functional groups for chemically modifying the target protein. Certain diseases’ causation (such as neuronal pathologies, cancer, disturbed metabolic conditions, and autoimmune disorders) have been correlated to specific mutations of aminoacyl-tRNA synthetases. Charcot-Marie-Tooth (CMT) is the most frequent heritable disorder of the peripheral nervous system (a neuronal disease) and
969-546: Is known as the DALR domain after characteristic conserved amino acids . Aminoacyl-tRNA synthetases have been kinetically studied, showing that Mg ions play an active catalytic role and therefore aaRs have a degree of magnesium dependence. Increasing the Mg concentration leads to an increase in the equilibrium constants for the aminoacyl-tRNA synthetases’ reactions. Although this trend was seen in both class I and class II synthetases,
1020-422: Is providing additional regulation of biological processes. There exists a theory that the increasing number of aaRSs that add domains is due to the continuous evolution of higher organisms with more complex and efficient building blocks and biological mechanisms. One key piece of evidence to this theory is that after a new domain is added to an aaRS, the domain becomes fully integrated. This new domain's functionality
1071-485: Is so called to reflect its large size and apparent Gram-staining properties. Mimivirus has a large and complex genome compared with most other viruses. Until 2013, when a larger virus Pandoravirus was described, it had the largest capsid diameter of all known viruses. APMV was discovered accidentally in 1992 within the amoeba Acanthamoeba polyphaga , after which it is named, during research into legionellosis by researchers from Marseille and Leeds. The virus
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#17327752869181122-492: Is that there were three distinct types of DNA viruses that were involved in generating the three known domains of life— eukarya , archaea and bacteria . It has been suggested that Mimivirus and similar kinds are remnants of a "fourth domain" of life, and that other giant virus may represent other ancient domains. Nevertheless, mimivirus does not exhibit the following characteristics, all of which are part of many conventional definitions of life : Giant virus While
1173-896: Is then used during translation. The presence of four aminoacyl tRNA synthetase encoding genes in mimivirus and mamavirus genomes, both species within the Mimiviridae family, as well as the discovery of seven aminoacyl tRNA synthetase genes in the megavirus genome (including those in Mimiviridae ) provide evidence that these large DNA viruses may have evolved from a shared cellular genome ancestor by means of genome reduction . The discovery and subsequent characterization of giant viruses has triggered debate on their evolutionary origins. The two main hypotheses are that they evolved from small viruses by picking up DNA from host organisms; or that they evolved from very complicated organisms via genome reduction , losing various functions including self-reproduction. The possible complicated ancestral organism
1224-566: The TCA cycle , fermentation, and the cytoskeleton . The first giant viruses to be described were chloroviruses of the family Phycodnaviridae . These were discovered in 1981 by Russel H. Meints, James L. Van Etten, Daniel Kuczmarski, Kit Lee, and Barbara Ang. The first chlorovirus was initially called HVCV (Hydra viridis Chlorella virus) since it was first found to infect Chlorella-like algae. Other giant viruses that infected marine flagellates were described later. The first mimivirus (BV-PW1)
1275-465: The hydroxyl (-OH) group of the adenosine via the carboxyl (-COOH) group. Regardless of where the aminoacyl is initially attached to the nucleotide, the 2'- O -aminoacyl-tRNA will ultimately migrate to the 3' position via transesterification . Bacterial aminoacyl-tRNA synthetases can be grouped as follows: Amino acids which use class II aaRS seem to be evolutionarily older. Both classes of aminoacyl-tRNA synthetases are multidomain proteins. In
1326-402: The transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA . In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code . This is sometimes called "charging" or "loading" the tRNA with an amino acid. Once the tRNA is charged,
1377-482: The "size" of the virion being casually listed as anywhere between 400 nm and 800 nm, depending on whether total length or capsid diameter is actually quoted. Its capsid appears hexagonal under an electron microscope , therefore the capsid symmetry is icosahedral. It does not appear to possess an outer viral envelope, suggesting that the virus does not exit the host cell by exocytosis . Mimivirus shares several morphological characteristics with all members of
1428-497: The NCLDV group of viruses. The condensed central core of the virion appears as a dark region under the electron microscope. The large genome of the virus resides within this area. An internal lipid layer surrounding the central core is present in all other NCLDV viruses, so this features may also be present in mimivirus. Several mRNA transcripts can be recovered from purified virions. Like other NCLDVs, transcripts for DNA polymerase ,
1479-526: The aaRSs of a given class are found to be homologous to one another, whereas class I and class II aaRSs are unrelated to one another. The class I aaRSs feature a cytidylyltransferase-like Rossmann fold seen in proteins like glycerol-3-phosphate cytidylyltransferase, nicotinamide nucleotide adenylyltransferase and archaeal FAD synthase, whereas the class II aaRSs have a unique fold related to biotin and lipoate ligases. The alpha helical anticodon binding domain of arginyl-, glycyl- and cysteinyl-tRNA synthetases
1530-419: The appropriate tRNA molecule's D arm , and the amino acid is transferred from the aa-AMP to either the 2'- or the 3'-OH of the last tRNA nucleotide (A76) at the 3'-end . The mechanism can be summarized in the following reaction series: Summing the reactions, the highly exergonic overall reaction is as follows: Some synthetases also mediate an editing reaction to ensure high fidelity of tRNA charging. If
1581-536: The cell. 8 hours after infection many mimivirus virions are clearly visible within the cell. The cell cytoplasm continues to fill with newly synthesised virions, and about 24 hours after initial infection the cell likely bursts open to release the new mimivirus virions. Little is known about the details of this replication cycle, most obviously attachment to the cell surface and entry, viral core release, DNA replication, transcription, translation, assembly and release of progeny virions. However, scientists have established
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1632-437: The debate over the origins of life . Some genes that code for characteristics unique to Mimivirus , including those coding for the capsid , have been conserved in a variety of viruses which infect organisms from all domains. This has been used to suggest that Mimivirus is related to a type of DNA virus that emerged before cellular organisms and played a key role in the development of all life on Earth. An alternative hypothesis
1683-409: The evolutionary history of aaRSs. A widespread belief in the evolutionary stability of this superfamily, meaning that every organism has all the aaRSs for their corresponding amino acids, is misconceived. A large-scale genomic analysis on ~2500 prokaryotic genomes showed that many of them miss one or more aaRS genes whereas many genomes have 1 or more paralogs. AlaRS, GlyRS, LeuRS, IleRS and ValRS are
1734-420: The exact criteria as defined in the scientific literature vary, giant viruses are generally described as viruses having large, pseudo- icosahedral capsids (200 to 400 nanometers in diameter) that may be surrounded by a thick (approximately 100 nm) layer of filamentous protein fibers. The viruses have large, double-stranded DNA genomes (300 to >1000 kilobasepairs) that encode a large contingent of genes (of
1785-435: The fidelity of replication. A stargate is a five-pronged star structure present on the viral capsid forming the portal through which the internal core of the particle is delivered to the host's cytoplasm. Aminoacyl tRNA synthetase An aminoacyl-tRNA synthetase ( aaRS or ARS ), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA . It does so by catalyzing
1836-466: The general NCLDV group. The mimivirus is the fourth-largest virus, after the Megavirus chilensis , Pandoravirus and Pithovirus . Mimivirus has a capsid diameter of 400 nm . Protein filaments measuring 100 nm project from the surface of the capsid, bringing the total length of the virus up to 600 nm. Variation in scientific literature renders these figures as highly approximate, with
1887-430: The general overview given above using electron micrographs of infected cells. These micrographs show mimivirus capsid assembly in the nucleus, acquisition of an inner lipid membrane via budding from the nucleus, and particles similar to those found in many other viruses, including all NCLDV members. These particles are known in other viruses as viral factories and allow efficient viral assembly by modifying large areas of
1938-496: The genetic code, beyond the twenty canonical amino acids found in nature, to include an unnatural amino acid as well. The unnatural amino acid is coded by a nonsense (TAG, TGA, TAA) triplet, a quadruplet codon, or in some cases a redundant rare codon. The organism that expresses the mutant synthetase can then be genetically programmed to incorporate the unnatural amino acid into any desired position in any protein of interest, allowing biochemists or structural biologists to probe or change
1989-444: The genome was of coding capacity, with the other 10% being " junk DNA ". The stages of mimivirus replication are not well known, but as a minimum it is known that mimivirus attaches to a chemical receptor on the surface of an amoeba cell and is taken into the cell. Once inside, an eclipse phase begins, in which the virus disappears and all appears normal within the cell. After about 4 hours small accumulations can be seen in areas of
2040-461: The host cell. Mimivirus may be a causative agent of some forms of pneumonia ; this is based mainly on indirect evidence in the form of antibodies to the virus discovered in pneumonia patients. However, the classification of mimivirus as a pathogen is tenuous at present as there have been only a couple of papers published potentially linking mimivirus to actual cases of pneumonia. A significant fraction of pneumonia cases are of unknown cause, though
2091-479: The incorrect tRNA is added (aka. the tRNA is found to be improperly charged), the aminoacyl-tRNA bond is hydrolyzed . This can happen when two amino acids have different properties even if they have similar shapes—as is the case with valine and threonine . The accuracy of aminoacyl-tRNA synthetase is so high that it is often paired with the word "superspecificity” when it is compared to other enzymes that are involved in metabolism. Although not all synthetases have
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2142-448: The largest known for viruses, and contain genes that encode for important elements of translation machinery, a characteristic that had previously been believed to be indicative of cellular organisms. These genes include multiple genes encoding a number of aminoacyl tRNA synthetases , enzymes that catalyze the esterification of specific amino acids or their precursors to their corresponding cognate tRNAs to form an aminoacyl tRNA that
2193-406: The magnesium dependence for the two classes are very distinct. Class II synthetases have two or (more frequently) three Mg ions, while class I only requires one Mg ion. Beside their lack of overall sequence and structure similarity, class I and class II synthetases feature different ATP recognition mechanisms. While class I binds via interactions mediated by backbone hydrogen bonds, class II uses
2244-468: The minimum 4 genes required for viruses to exist ( c.f. MS2 and Qβ viruses). Analysis of its genome revealed the presence of genes not seen in any other viruses, including aminoacyl tRNA synthetases , and other genes previously thought only to be encoded by cellular organisms. Like other large DNA viruses, mimivirus contains several genes for sugar, lipid and amino acid metabolism, as well as some metabolic genes not found in any other virus. Roughly 90% of
2295-437: The most evolutionarily stable members of the family. GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes. With the exception of AlaRS, it has been discovered that 19 out of the 20 human aaRSs have added at least one new domain or motif. These new domains and motifs vary in function and are observed in various forms of life. A common novel function within human aaRSs
2346-643: The order of 1000 genes). The best characterized giant viruses are the phylogenetically related mimivirus and megavirus , which belong to the family Mimiviridae (aka Megaviridae ), and are distinguished by their large capsid diameters. Giant viruses from the deep ocean, terrestrial sources, and human patients contain genes encoding cytochrome P450 (CYP; P450) enzymes . The origin of these P450 genes in giant viruses remains unknown but may have been acquired from an ancient host. The genomes of many giant viruses encode many unusual genes that are not found in other viruses, including genes involved in glycolysis and
2397-673: The protein's function. For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural amino acid with a reactive side-chain into the binding site, create a new protein that cuts the DNA at the target-sequence, rather than binding it. By mutating aminoacyl tRNA synthetases, chemists have expanded the genetic codes of various organisms to include lab-synthesized amino acids with all kinds of useful properties: photoreactive, metal-chelating, xenon-chelating, crosslinking, spin-resonant, fluorescent, biotinylated, and redox-active amino acids. Another use
2448-445: The so-called canonical phylogenetic pattern shown by most other enzymes for the three domains of life - Archaea , Bacteria , and Eukarya . Furthermore, the phylogenies inferred for aaRSs of different amino acids often do not agree with one another. In addition, aaRS paralogs within the same species show a high degree of divergence between them. These are clear indications that horizontal transfer has occurred several times during
2499-476: Was described in 1995, but was not recognized as such until its sequenced genome was released as Cafeteria roenbergensis virus (CroV) in 2010. Subsequently, the Giant Virus Acanthamoeba polyphaga Mimivirus was characterized (which had been mistaken as a bacterium in 1993), and then sequenced. The term "girus" was coined to refer to the group in 2006. The genomes of giant viruses are
2550-453: Was discovered that aminoacyl-trna synthetases may incorporate alternative amino acids during shortages of their precursors. In particular, tryptophanyl -tRNA synthetase ( WARS1 ) will incorporate phenylalanine during tryptophan depletion, essentially inducing a W>F codon reassignment . Depletion of the other substrate of aminoacyl-tRNA synthetases, the cognate tRNA, may be relevant to certain diseases, e.g. Charcot–Marie–Tooth disease . It
2601-601: Was observed in a Gram stain and mistakenly thought to be a Gram-positive bacterium . As a consequence it was named Bradfordcoccus , after Bradford , England, where the amoeba had originated. In 2003, researchers at the Université de la Méditerranée in Marseille , France, published a paper in Science identifying the micro-organism as a virus. It was given the name "mimivirus" (for "mimicking microbe") as it resembles
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