114-566: Variants: CRISPR ( / ˈ k r ɪ s p ər / ) (an acronym for c lustered r egularly i nterspaced s hort p alindromic r epeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea . Each sequence within an individual prokaryotic cell is derived from a DNA fragment of a bacteriophage that had previously infected the prokaryote or one of its ancestors. These sequences are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play
228-428: A numeronym . For example, "i18n" abbreviates " internationalization ", a computer-science term for adapting software for worldwide use; the "18" represents the 18 letters that come between the first and the last in "internationalization". Similarly, "localization" can be abbreviated "l10n"; " multilingualization " "m17n"; and " accessibility " "a11y". In addition to the use of a specific number replacing that many letters,
342-645: A single word ("television" or "transvestite", for instance), and is in general spelled without punctuation (except in the plural). Although "PS" stands for the single English word " postscript " or the Latin postscriptum , it is often spelled with periods ("P.S.") as if parsed as Latin post scriptum instead. The slash ('/', or solidus ) is sometimes used to separate the letters in an acronym, as in "N/A" ("not applicable, not available") and "c/o" ("care of"). Inconveniently long words used frequently in related contexts can be represented according to their letter count as
456-600: A 'staggered' cut in double stranded DNA as opposed to the 'blunt' cut produced by Cas9, relying on a 'T rich' PAM (providing alternative targeting sites to Cas9), and requiring only a CRISPR RNA (crRNA) for successful targeting. By contrast, Cas9 requires both crRNA and a trans-activating crRNA (tracrRNA). These differences may give Cas12a some advantages over Cas9. For example, Cas12a's small crRNAs are ideal for multiplexed genome editing, as more of them can be packaged in one vector than can Cas9's sgRNAs. The sticky 5′ overhangs left by Cas12a can also be used for DNA assembly that
570-507: A 1940 translation of a novel by the German writer Lion Feuchtwanger . It is an unsettled question in English lexicography and style guides whether it is legitimate to use the word acronym to describe forms that use initials but are not pronounced as a word. While there is plenty of evidence that acronym is used widely in this way, some sources do not acknowledge this usage, reserving
684-417: A 2015 paper by Chinese scientists P. Liang and Y. Xu. The system made a successful cleavage of mutant Beta-Hemoglobin ( HBB ) in 28 out of 54 embryos. Four out of the 28 embryos were successfully recombined using a donor template. The scientists showed that during DNA recombination of the cleaved strand, the homologous endogenous sequence HBD competes with the exogenous donor template. DNA repair in human embryos
798-524: A PAM sequence, with the other end of the spacer cut using a ruler mechanism, thus maintaining the regularity of the spacer size in the CRISPR array. The conservation of the PAM sequence differs between CRISPR-Cas systems and appears to be evolutionarily linked to Cas1 and the leader sequence . New spacers are added to a CRISPR array in a directional manner, occurring preferentially, but not exclusively, adjacent to
912-586: A cluster of interrupted direct repeats (DR) in that bacterium. They recognized the diversity of the sequences that intervened in the direct repeats among different strains of M. tuberculosis and used this property to design a typing method called spoligotyping , still in use today. Francisco Mojica at the University of Alicante in Spain studied the function of repeats in the archaeal species Haloferax and Haloarcula . Mojica's supervisor surmised that
1026-530: A complex of Cas proteins called Cascade, that in E. coli cut the CRISPR RNA precursor within the repeats into mature spacer-containing RNA molecules called CRISPR RNA (crRNA), which remained bound to the protein complex. Moreover, it was found that Cascade, crRNA and a helicase/nuclease ( Cas3 ) were required to provide a bacterial host with immunity against infection by a DNA virus . By designing an anti-virus CRISPR, they demonstrated that two orientations of
1140-417: A different Cas protein in the complex, Cas10. The DNA cleavage was shown to be transcription dependent. The mechanism for distinguishing self from foreign DNA during interference is built into the crRNAs and is therefore likely common to all three systems. Throughout the distinctive maturation process of each major type, all crRNAs contain a spacer sequence and some portion of the repeat at one or both ends. It
1254-625: A different meaning. Medical literature has been struggling to control the proliferation of acronyms, including efforts by the American Academy of Dermatology. Acronyms are often taught as mnemonic devices: for example the colors of the rainbow are ROY G. BIV (red, orange, yellow, green, blue, indigo, violet). They are also used as mental checklists: in aviation GUMPS stands for gas-undercarriage-mixture-propeller-seat belts. Other mnemonic acronyms include CAN SLIM in finance, PAVPANIC in English grammar, and PEMDAS in mathematics. It
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#17327730741981368-410: A key role in the antiviral (i.e. anti- phage ) defense system of prokaryotes and provide a form of heritable, acquired immunity . CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea. Cas9 (or "CRISPR-associated protein 9") is an enzyme that uses CRISPR sequences as a guide to recognize and open up specific strands of DNA that are complementary to
1482-781: A medial decimal point . Particularly in British and Commonwealth English , all such punctuation marking acronyms and other capitalized abbreviations is now uncommon and considered either unnecessary or incorrect. The presence of all-capital letters is now thought sufficient to indicate the nature of the UK , the EU , and the UN . Forms such as the U.S.A. for "the United States of America " are now considered to indicate American or North American English . Even within those dialects, such punctuation
1596-407: A period when the letters are pronounced individually, as in " K.G.B. ", but not when pronounced as a word, as in " NATO ". The logic of this style is that the pronunciation is reflected graphically by the punctuation scheme. When a multiple-letter abbreviation is formed from a single word, periods are in general not used, although they may be common in informal usage. "TV", for example, may stand for
1710-514: A phage infection, the sequence of the CRISPR spacer must correspond perfectly to the sequence of the target phage gene. Phages can continue to infect their hosts' given point mutations in the spacer. Similar stringency is required in PAM or the bacterial strain remains phage sensitive. A study of 124 S. thermophilus strains showed that 26% of all spacers were unique and that different CRISPR loci showed different rates of spacer acquisition. Some CRISPR loci evolve more rapidly than others, which allowed
1824-549: A role for the RNA transcript of spacers on target recognition in a mechanism that could be analogous to the RNA interference system used by eukaryotic cells. Koonin and colleagues extended this RNA interference hypothesis by proposing mechanisms of action for the different CRISPR-Cas subtypes according to the predicted function of their proteins. Experimental work by several groups revealed the basic mechanisms of CRISPR-Cas immunity. In 2007,
1938-420: A role in the dynamic structure of the CRISPR loci. In this publication, the acronym CRISPR was used as the universal name of this pattern, but its function remained enigmatic. In 2005, three independent research groups showed that some CRISPR spacers are derived from phage DNA and extrachromosomal DNA such as plasmids . In effect, the spacers are fragments of DNA gathered from viruses that previously attacked
2052-476: A sequence-independent manner. Representative Cas2 proteins have been characterised and possess either (single strand) ssRNA- or (double strand) dsDNA- specific endoribonuclease activity. In the I-E system of E. coli Cas1 and Cas2 form a complex where a Cas2 dimer bridges two Cas1 dimers. In this complex Cas2 performs a non-enzymatic scaffolding role, binding double-stranded fragments of invading DNA, while Cas1 binds
2166-408: A single long transcript encompassing much of the CRISPR array. This transcript is then cleaved by Cas proteins to form crRNAs. The mechanism to produce crRNAs differs among CRISPR-Cas systems. In type I-E and type I-F systems, the proteins Cas6e and Cas6f respectively, recognise stem-loops created by the pairing of identical repeats that flank the crRNA. These Cas proteins cleave the longer transcript at
2280-561: A single phage. During the same interval, the phage developed single-nucleotide polymorphisms that became fixed in the population, suggesting that targeting had prevented phage replication absent these mutations. Another S. thermophilus experiment showed that phages can infect and replicate in hosts that have only one targeting spacer. Yet another showed that sensitive hosts can exist in environments with high-phage titres. The chemostat and observational studies suggest many nuances to CRISPR and phage (co)evolution. Acronym An acronym
2394-436: A single word, such as NATO (as distinct from B-B-C )" but adds later "In everyday use, acronym is often applied to abbreviations that are technically initialisms, since they are pronounced as separate letters." The Chicago Manual of Style acknowledges the complexity ("Furthermore, an acronym and initialism are occasionally combined (JPEG), and the line between initialism and acronym is not always clear") but still defines
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#17327730741982508-515: A twentieth-century phenomenon. Linguist David Wilton in Word Myths: Debunking Linguistic Urban Legends claims that "forming words from acronyms is a distinctly twentieth- (and now twenty-first-) century phenomenon. There is only one known pre-twentieth-century [English] word with an acronymic origin and it was in vogue for only a short time in 1886. The word is colinderies or colinda , an acronym for
2622-709: A wide range of organisms, including baker's yeast ( Saccharomyces cerevisiae ), the opportunistic pathogen Candida albicans , zebrafish ( Danio rerio ), fruit flies ( Drosophila melanogaster ), ants ( Harpegnathos saltator and Ooceraea biroi ), mosquitoes ( Aedes aegypti ), nematodes ( Caenorhabditis elegans ), plants, mice ( Mus musculus domesticus ) , monkeys and human embryos. CRISPR has been modified to make programmable transcription factors that allows activation or silencing of targeted genes. The CRISPR-Cas9 system has been shown to make effective gene edits in Human tripronuclear zygotes , as first described in
2736-502: A word rather than as a sequence of letters. In this sense, NASA / ˈ n æ s ə / is an acronym but USA / j uː ɛ s ˈ eɪ / is not. The broader sense of acronym , ignoring pronunciation, is its original meaning and in common use. Dictionary and style-guide editors dispute whether the term acronym can be legitimately applied to abbreviations which are not pronounced as words, and they do not agree on acronym spacing , casing , and punctuation . The phrase that
2850-471: A word, an abbreviation is not an acronym." In contrast, some style guides do support it, whether explicitly or implicitly. The 1994 edition of Merriam-Webster's Dictionary of English Usage defends the usage on the basis of a claim that dictionaries do not make a distinction. The BuzzFeed style guide describes CBS and PBS as "acronyms ending in S". Acronymy, like retronymy , is a linguistic process that has existed throughout history but for which there
2964-677: A word. American English dictionaries such as Merriam-Webster , Dictionary.com's Random House Webster's Unabridged Dictionary and the American Heritage Dictionary as well as the British Oxford English Dictionary and the Australian Macquarie Dictionary all include a sense in their entries for acronym equating it with initialism , although The American Heritage Dictionary criticizes it with
3078-488: Is a question about how to pluralize acronyms. Often a writer will add an 's' following an apostrophe, as in "PC's". However, Kate L. Turabian 's A Manual for Writers of Research Papers, Theses, and Dissertations , writing about style in academic writings, allows for an apostrophe to form plural acronyms "only when an abbreviation contains internal periods or both capital and lowercase letters". Turabian would therefore prefer "DVDs" and "URLs" but "Ph.D.'s". The style guides of
3192-425: Is a type of abbreviation consisting of a phrase whose only pronounced elements are the initial letters or initial sounds of words inside that phrase. Acronyms are often spelled with the initial letter of each word in all caps with no punctuation . For some, an initialism or alphabetism , connotes this general meaning, and an acronym is a subset with a narrower definition: an initialism pronounced as
3306-721: Is becoming increasingly uncommon. Some style guides , such as that of the BBC , no longer require punctuation to show ellipsis ; some even proscribe it. Larry Trask , American author of The Penguin Guide to Punctuation , states categorically that, in British English , "this tiresome and unnecessary practice is now obsolete." Nevertheless, some influential style guides , many of them American , still require periods in certain instances. For example, The New York Times Manual of Style and Usage recommends following each segment with
3420-411: Is common for grammatical contractions (e.g. don't , y'all , and ain't ) and for contractions marking unusual pronunciations (e.g. a'ight , cap'n , and fo'c'sle for "all right", "captain", and "forecastle"). By the early twentieth century, it was standard to use a full stop/period/point , especially in the cases of initialisms and acronyms. Previously, especially for Latin abbreviations , this
3534-544: Is complementary to the repeat sequence, known as a trans-activating crRNA (tracrRNA). Transcription of the tracrRNA and the primary CRISPR transcript results in base pairing and the formation of dsRNA at the repeat sequence, which is subsequently targeted by RNaseIII to produce crRNAs. Unlike the other two systems, the crRNA does not contain the full spacer, which is instead truncated at one end. CrRNAs associate with Cas proteins to form ribonucleotide complexes that recognize foreign nucleic acids. CrRNAs show no preference between
CRISPR - Misplaced Pages Continue
3648-590: Is divided into types II, V, and VI. The 6 system types are divided into 33 subtypes. Each type and most subtypes are characterized by a "signature gene" found almost exclusively in the category. Classification is also based on the complement of cas genes that are present. Most CRISPR-Cas systems have a Cas1 protein. The phylogeny of Cas1 proteins generally agrees with the classification system, but exceptions exist due to module shuffling. Many organisms contain multiple CRISPR-Cas systems suggesting that they are compatible and may share components. The sporadic distribution of
3762-631: Is especially important for paper media, where no search utility is available to find the first use.) It also gives students a convenient review list to memorize the important acronyms introduced in a textbook chapter. Expansion at first use and abbreviation keys originated in the print era, but they are equally useful for electronic text . While acronyms provide convenience and succinctness for specialists, they often degenerate into confusing jargon . This may be intentional, to exclude readers without domain-specific knowledge. New acronyms may also confuse when they coincide with an already existing acronym having
3876-464: Is generally said as two letters, but IPsec for Internet Protocol Security is usually pronounced as / ˌ aɪ ˈ p iː s ɛ k / or / ˈ ɪ p s ɛ k / , along with variant capitalization like "IPSEC" and "Ipsec". Pronunciation may even vary within a single speaker's vocabulary, depending on narrow contexts. As an example, the database programming language SQL is usually said as three letters, but in reference to Microsoft's implementation
3990-445: Is hard to trace. The non-random evolution of these spacer regions has been found to be highly dependent on the environment and the particular foreign mobile genetic elements it contains. CRISPR-Cas can immunize bacteria against certain phages and thus halt transmission. For this reason, Koonin described CRISPR-Cas as a Lamarckian inheritance mechanism. However, this was disputed by a critic who noted, "We should remember [Lamarck] for
4104-451: Is made up of an AT-rich leader sequence followed by short repeats that are separated by unique spacers. CRISPR repeats typically range in size from 28 to 37 base pairs (bps), though there can be as few as 23 bp and as many as 55 bp. Some show dyad symmetry , implying the formation of a secondary structure such as a stem-loop ('hairpin') in the RNA, while others are designed to be unstructured. The size of spacers in different CRISPR arrays
4218-577: Is much more complicated and particular than in derived stem cells. In 2015, the nuclease Cas12a (formerly called Cpf1 ) was characterized in the CRISPR-Cpf1 system of the bacterium Francisella novicida . Its original name, from a TIGRFAMs protein family definition built in 2012, reflects the prevalence of its CRISPR-Cas subtype in the Prevotella and Francisella lineages. Cas12a showed several key differences from Cas9 including: causing
4332-462: Is much more target-specific than traditional restriction enzyme cloning. Finally, Cas12a cleaves DNA 18–23 base pairs downstream from the PAM site. This means there is no disruption to the recognition sequence after repair, and so Cas12a enables multiple rounds of DNA cleavage. By contrast, since Cas9 cuts only 3 base pairs upstream of the PAM site, the NHEJ pathway results in indel mutations that destroy
4446-459: Is not uncommon for acronyms to be cited in a kind of false etymology , called a folk etymology , for a word. Such etymologies persist in popular culture but have no factual basis in historical linguistics , and are examples of language-related urban legends . For example, " cop " is commonly cited as being derived, it is presumed, from "constable on patrol", and " posh " from " port outward, starboard home ". With some of these specious expansions,
4560-511: Is the partial repeat sequence that prevents the CRISPR-Cas system from targeting the chromosome as base pairing beyond the spacer sequence signals self and prevents DNA cleavage. RNA-guided CRISPR enzymes are classified as type V restriction enzymes . The cas genes in the adaptor and effector modules of the CRISPR-Cas system are believed to have evolved from two different ancestral modules. A transposon -like element called casposon encoding
4674-415: Is traditionally pronounced like the word sequel . In writing for a broad audience, the words of an acronym are typically written out in full at its first occurrence within a given text. Expansion At First Use (EAFU) benefits readers unfamiliar with the acronym. Another text aid is an abbreviation key which lists and expands all acronyms used, a reference for readers who skipped past the first use. (This
CRISPR - Misplaced Pages Continue
4788-422: Is typically 32 to 38 bp (range 21 to 72 bp). New spacers can appear rapidly as part of the immune response to phage infection. There are usually fewer than 50 units of the repeat-spacer sequence in a CRISPR array. Small clusters of cas genes are often located next to CRISPR repeat-spacer arrays. Collectively the 93 cas genes are grouped into 35 families based on sequence similarity of the encoded proteins. 11 of
4902-516: The Colonial and Indian Exposition held in London in that year." However, although acronymic words seem not to have been employed in general vocabulary before the twentieth century (as Wilton points out), the concept of their formation is treated as effortlessly understood (and evidently not novel) in an Edgar Allan Poe story of the 1830s, " How to Write a Blackwood Article ", which includes
5016-623: The Modern Language Association and American Psychological Association prohibit apostrophes from being used to pluralize acronyms regardless of periods (so "compact discs" would be "CDs" or "C.D.s"), whereas The New York Times Manual of Style and Usage requires an apostrophe when pluralizing all abbreviations regardless of periods (preferring "PC's, TV's and VCR's"). Possessive plurals that also include apostrophes for mere pluralization and periods appear especially complex: for example, "the C.D.'s' labels" (the labels of
5130-517: The Nobel Prize in Chemistry in 2020 awarded to Emmanuelle Charpentier and Jennifer Doudna . The discovery of clustered DNA repeats took place independently in three parts of the world. The first description of what would later be called CRISPR is from Osaka University researcher Yoshizumi Ishino and his colleagues in 1987. They accidentally cloned part of a CRISPR sequence together with
5244-539: The Restoration witticism arranging the names of some members of Charles II 's Committee for Foreign Affairs to produce the "CABAL" ministry . OK , a term of disputed origin, dates back at least to the early nineteenth century and is now used around the world. Acronyms are used most often to abbreviate names of organizations and long or frequently referenced terms. The armed forces and government agencies frequently employ acronyms; some well-known examples from
5358-410: The S. thermophilus CRISPR system can also be reprogrammed to target a site of their choosing by changing the sequence of its crRNA. These advances fueled efforts to edit genomes with the modified CRISPR-Cas9 system. Groups led by Feng Zhang and George Church simultaneously published descriptions of genome editing in human cell cultures using CRISPR-Cas9 for the first time. It has since been used in
5472-498: The " iap" gene (isozyme conversion of alkaline phosphatase) from their target genome, that of Escherichia coli . The organization of the repeats was unusual. Repeated sequences are typically arranged consecutively, without interspersing different sequences. They did not know the function of the interrupted clustered repeats. In 1993, researchers of Mycobacterium tuberculosis in the Netherlands published two articles about
5586-480: The "belief" that the etymology is acronymic has clearly been tongue-in-cheek among many citers, as with "gentlemen only, ladies forbidden" for " golf ", although many other (more credulous ) people have uncritically taken it for fact. Taboo words in particular commonly have such false etymologies: " shit " from "ship/store high in transit" or "special high-intensity training" and " fuck " from "for unlawful carnal knowledge", or "fornication under consent/command of
5700-463: The 160-character SMS limit, and to save time, acronyms such as "GF" ("girlfriend"), "LOL" ("laughing out loud"), and "DL" ("download" or "down low") have become popular. Some prescriptivists disdain texting acronyms and abbreviations as decreasing clarity, or as failure to use "pure" or "proper" English. Others point out that languages have always continually changed , and argue that acronyms should be embraced as inevitable, or as innovation that adapts
5814-461: The 18 letters between the initial "i" and the final "n"). Authors of expository writing will sometimes capitalize or otherwise distinctively format the initials of the expansion for pedagogical emphasis (for example, writing: "the onset of Congestive Heart Failure (CHF)" or "the onset of c ongestive h eart f ailure (CHF)"). Capitalization like this, however, conflicts with the convention of English orthography, which generally reserves capitals in
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#17327730741985928-426: The 35 families form the cas core, which includes the protein families Cas1 through Cas9. A complete CRISPR-Cas locus has at least one gene belonging to the cas core. CRISPR-Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2
6042-466: The British press may render it "Nato"), but uses lower case in " Unicef " (from "United Nations International Children's Emergency Fund") because it is more than four letters, and to style it in caps might look ungainly (flirting with the appearance of "shouting capitals"). While abbreviations typically exclude the initials of short function words (such as "and", "or", "of", or "to"), this is not always
6156-476: The CRISPR sequence. Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR-Cas9 that can be used to edit genes within living organisms. This editing process has a wide variety of applications including basic biological research, development of biotechnological products, and treatment of diseases. The development of the CRISPR-Cas9 genome editing technique was recognized by
6270-413: The CRISPR-Cas subtypes suggests that the CRISPR-Cas system is subject to horizontal gene transfer during microbial evolution . CRISPR-Cas immunity is a natural process of bacteria and archaea. CRISPR-Cas prevents bacteriophage infection, conjugation and natural transformation by degrading foreign nucleic acids that enter the cell. When a microbe is invaded by a bacteriophage , the first stage of
6384-506: The Cas1-like integrase and potentially other components of the adaptation module was inserted next to the ancestral effector module, which likely functioned as an independent innate immune system. The highly conserved cas1 and cas2 genes of the adaptor module evolved from the ancestral module while a variety of class 1 effector cas genes evolved from the ancestral effector module. The evolution of these various class 1 effector module cas genes
6498-452: The DNA target specified by the guide RNA. This contribution was so significant that it was recognized by the Nobel Prize in Chemistry in 2020. By manipulating the nucleotide sequence of the guide RNA, the artificial Cas9 system could be programmed to target any DNA sequence for separation. Another collaboration comprising Virginijus Šikšnys , Gasiūnas, Barrangou, and Horvath showed that Cas9 from
6612-572: The Danish food company Danisco, then developed phage-resistant S. thermophilus strains for yogurt production. Danisco was later bought by DuPont , which owns about 50 percent of the global dairy culture market, and the technology spread widely. A major advance in understanding CRISPR came with Jansen's observation that the prokaryote repeat cluster was accompanied by four homologous genes that make up CRISPR-associated systems, cas 1–4. The Cas proteins showed helicase and nuclease motifs , suggesting
6726-467: The PAM is recognized on the same strand as the crRNA (the opposite strand to type I systems). Type III systems, like type I require six or seven Cas proteins binding to crRNAs. The type III systems analysed from S. solfataricus and P. furiosus both target the mRNA of phages rather than phage DNA genome, which may make these systems uniquely capable of targeting RNA-based phage genomes. Type III systems were also found to target DNA in addition to RNA using
6840-564: The U.S. Navy, is "COMCRUDESPAC", which stands for "commander, cruisers destroyers Pacific"; it is also seen as "ComCruDesPac". Inventors are encouraged to anticipate the formation of acronyms by making new terms "YABA-compatible" ("yet another bloody acronym"), meaning the term's acronym can be pronounced and is not an offensive word: "When choosing a new name, be sure it is 'YABA-compatible'." Acronym use has been further popularized by text messaging on mobile phones with short message service (SMS), and instant messenger (IM). To fit messages into
6954-560: The United States are among the " alphabet agencies " (jokingly referred to as " alphabet soup ") created under the New Deal by Franklin D. Roosevelt (himself known as "FDR"). Business and industry also coin acronyms prolifically. The rapid advance of science and technology also drives the usage, as new inventions and concepts with multiword names create a demand for shorter, more pronounceable names. One representative example, from
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#17327730741987068-411: The acronym may use normal case rules, e.g. it would appear generally in lower case, but with an initial capital when starting a sentence or when in a title. Once knowledge of the words underlying such an acronym has faded from common recall, the acronym may be termed an anacronym . Examples of anacronyms are the words " scuba ", " radar ", and " laser ". The word "an acro nym" should not be confused with
7182-545: The acronym stands for is called its expansion . The meaning of an acronym includes both its expansion and the meaning of its expansion. The word acronym is formed from the Greek roots akro- , meaning 'height, summit, or tip', and -nym , 'name'. This neoclassical compound appears to have originated in German , with attestations for the German form Akronym appearing as early as 1921. Citations in English date to
7296-590: The adoption of acronyms was modern warfare, with its many highly technical terms. While there is no recorded use of military acronyms dating from the American Civil War (acronyms such as "ANV" for " Army of Northern Virginia " post-date the war itself), they became somewhat common in World War I , and by World War II they were widespread even in the slang of soldiers, who referred to themselves as G.I.s . The widespread, frequent use of acronyms across
7410-506: The apostrophe should be reserved for the possessive ("the TV's antenna"). In some languages, the convention of doubling the letters in the acronym is used to indicate plural words: for example, the Spanish EE.UU. , for Estados Unidos ('United States'). This old convention is still sometimes followed for a limited number of English abbreviations, such as SS. for Saints , pp. for
7524-1163: The case. Sometimes function words are included to make a pronounceable acronym, such as CORE ( Congress of Racial Equality ). Sometimes the letters representing these words are written in lower case, such as in the cases of "TfL" (" Transport for London ") and LotR ( The Lord of the Rings ); this usually occurs when the acronym represents a multi-word proper noun. Numbers (both cardinal and ordinal ) in names are often represented by digits rather than initial letters, as in "4GL" (" fourth generation language ") or "G77" (" Group of 77 "). Large numbers may use metric prefixes , as with " Y2K " for "Year 2000". Exceptions using initials for numbers include " TLA " ("three-letter acronym/abbreviation") and "GoF" (" Gang of Four "). Abbreviations using numbers for other purposes include repetitions, such as " A2DP " ("Advanced Audio Distribution Profile"), " W3C " ("World Wide Web Consortium"), and T3 ( Trends, Tips & Tools for Everyday Living ); pronunciation, such as " B2B " ("business to business"); and numeronyms , such as "i18n" ("internationalization"; "18" represents
7638-462: The cell. The source of the spacers was a sign that the CRISPR- cas system could have a role in adaptive immunity in bacteria . All three studies proposing this idea were initially rejected by high-profile journals, but eventually appeared in other journals. The first publication proposing a role of CRISPR-Cas in microbial immunity, by Mojica and collaborators at the University of Alicante , predicted
7752-559: The clustered repeats had a role in correctly segregating replicated DNA into daughter cells during cell division, because plasmids and chromosomes with identical repeat arrays could not coexist in Haloferax volcanii . Transcription of the interrupted repeats was also noted for the first time; this was the first full characterization of CRISPR. By 2000, Mojica and his students, after an automated search of published genomes, identified interrupted repeats in 20 species of microbes as belonging to
7866-407: The coding and non-coding strands, which is indicative of an RNA-guided DNA-targeting system. The type I-E complex (commonly referred to as Cascade) requires five Cas proteins bound to a single crRNA. During the interference stage in type I systems, the PAM sequence is recognized on the crRNA-complementary strand and is required along with crRNA annealing. In type I systems correct base pairing between
7980-413: The compact discs). In some instances, however, an apostrophe may increase clarity: for example, if the final letter of an abbreviation is "S", as in "SOS's" (although abbreviations ending with S can also take "-es", e.g. "SOSes"), or when pluralizing an abbreviation that has periods. A particularly rich source of options arises when the plural of an acronym would normally be indicated in a word other than
8094-564: The contrived acronym "P.R.E.T.T.Y.B.L.U.E.B.A.T.C.H." The use of Latin and Neo-Latin terms in vernaculars has been pan-European and pre-dates modern English. Some examples of acronyms in this class are: The earliest example of a word derived from an acronym listed by the OED is "abjud" (now " abjad "), formed from the original first four letters of the Arabic alphabet in the late eighteenth century. Some acrostics pre-date this, however, such as
8208-668: The crRNA (sense/antisense) provided immunity, indicating that the crRNA guides were targeting dsDNA . That year Marraffini and Sontheimer confirmed that a CRISPR sequence of S. epidermidis targeted DNA and not RNA to prevent conjugation . This finding was at odds with the proposed RNA-interference-like mechanism of CRISPR-Cas immunity, although a CRISPR-Cas system that targets foreign RNA was later found in Pyrococcus furiosus . A 2010 study showed that CRISPR-Cas cuts strands of both phage and plasmid DNA in S. thermophilus . A simpler CRISPR system from Streptococcus pyogenes relies on
8322-489: The crRNA and the protospacer signals a conformational change in Cascade that recruits Cas3 for DNA degradation. Type II systems rely on a single multifunctional protein, Cas9 , for the interference step. Cas9 requires both the crRNA and the tracrRNA to function and cleave DNA using its dual HNH and RuvC/RNaseH-like endonuclease domains. Basepairing between the PAM and the phage genome is required in type II systems. However,
8436-468: The development of various diagnostic technologies. In 2016, the nuclease Cas13a (formerly known as C2c2 ) from the bacterium Leptotrichia shahii was characterized. Cas13 is an RNA-guided RNA endonuclease, which means that it does not cleave DNA, but only single-stranded RNA. Cas13 is guided by its crRNA to a ssRNA target and binds and cleaves the target. Similar to Cas12a, the Cas13 remains bound to
8550-438: The dictionary entries and style guide recommendations regarding the term acronym through the twentieth century did not explicitly acknowledge or support the expansive sense. The Merriam–Webster's Dictionary of English Usage from 1994 is one of the earliest publications to advocate for the expansive sense, and all the major dictionary editions that include a sense of acronym equating it with initialism were first published in
8664-512: The edge of the paired region, leaving a single crRNA along with a small remnant of the paired repeat region. Type III systems also use Cas6, however, their repeats do not produce stem-loops. Cleavage instead occurs by the longer transcript wrapping around the Cas6 to allow cleavage just upstream of the repeat sequence. Type II systems lack the Cas6 gene and instead utilize RNaseIII for cleavage. Functional type II systems encode an extra small RNA that
8778-664: The exclusive sense for acronym and its earliest citation was from 1943. In early December 2010, Duke University researcher Stephen Goranson published a citation for acronym to the American Dialect Society e-mail discussion list which refers to PGN being pronounced "pee-gee-enn", antedating English language usage of the word to 1940. Linguist Ben Zimmer then mentioned this citation in his December 16, 2010 " On Language " column about acronyms in The New York Times Magazine . By 2011,
8892-405: The final position. It is likely that in those systems, a blunt end is generated at the very end of the direct repeat and the protospacer during acquisition. Analysis of Sulfolobus solfataricus CRISPRs revealed further complexities to the canonical model of spacer insertion, as one of its six CRISPR loci inserted new spacers randomly throughout its CRISPR array, as opposed to inserting closest to
9006-763: The final word if spelled out in full. A classic example is "Member of Parliament", which in plural is "Members of Parliament". It is possible then to abbreviate this as "M's P", which was fairly common in mid-twentieth-century Australian news writing (or similar ), and used by former Australian Prime Minister Ben Chifley . This usage is less common than forms with "s" at the end, such as "MPs", and may appear dated or pedantic. In common usage, therefore, "weapons of mass destruction" becomes "WMDs", "prisoners of war" becomes "POWs", and "runs batted in" becomes "RBIs". Abbreviations that come from single, rather than multiple, words – such as "TV" ("television") – are usually pluralized without apostrophes ("two TVs"); most writers feel that
9120-487: The first experimental evidence that CRISPR was an adaptive immune system was published. A CRISPR region in Streptococcus thermophilus acquired spacers from the DNA of an infecting bacteriophage . The researchers manipulated the resistance of S. thermophilus to different types of phages by adding and deleting spacers whose sequence matched those found in the tested phages. In 2008, Brouns and Van der Oost identified
9234-464: The first letter of acronyms, reserving all-caps styling for initialisms, writing the pronounced acronyms "Nato" and "Aids" in mixed case, but the initialisms "USA" and "FBI" in all caps. For example, this is the style used in The Guardian , and BBC News typically edits to this style (though its official style guide, dating from 2003, still recommends all-caps ). The logic of this style is that
9348-411: The first nt of the protospacer. This nt becomes the final base in the first direct repeat. This suggests that the spacer acquisition machinery generates single-stranded overhangs in the second-to-last position of the direct repeat and in the PAM during spacer insertion. However, not all CRISPR-Cas systems appear to share this mechanism as PAMs in other organisms do not show the same level of conservation in
9462-460: The genome of Archaeoglobus fulgidus were transcribed into long RNA molecules subsequently processed into unit-length small RNAs, plus some longer forms of 2, 3, or more spacer-repeat units. In 2005, yogurt researcher Rodolphe Barrangou discovered that Streptococcus thermophilus , after iterative phage infection challenges, develops increased phage resistance due to the incorporation of additional CRISPR spacer sequences. Barrangou's employer,
9576-466: The good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works". But as more recent studies have been conducted, it has become apparent that the acquired spacer regions of CRISPR-Cas systems are indeed a form of Lamarckian evolution because they are genetic mutations that are acquired and then passed on. On
9690-658: The immune response is to capture phage DNA and insert it into a CRISPR locus in the form of a spacer. Cas1 and Cas2 are found in both types of CRISPR-Cas immune systems, which indicates that they are involved in spacer acquisition. Mutation studies confirmed this hypothesis, showing that removal of Cas1 or Cas2 stopped spacer acquisition, without affecting CRISPR immune response. Multiple Cas1 proteins have been characterised and their structures resolved. Cas1 proteins have diverse amino acid sequences. However, their crystal structures are similar and all purified Cas1 proteins are metal-dependent nucleases/ integrases that bind to DNA in
9804-435: The king". In English, abbreviations have previously been marked by a wide variety of punctuation . Obsolete forms include using an overbar or colon to show the ellipsis of letters following the initial part. The forward slash is still common in many dialects for some fixed expressions—such as in w/ for "with" or A/C for " air conditioning "—while only infrequently being used to abbreviate new terms. The apostrophe
9918-500: The label "usage problem". However, many English language dictionaries, such as the Collins COBUILD Advanced Dictionary , Cambridge Advanced Learner's Dictionary , Macmillan Dictionary , Longman Dictionary of Contemporary English , New Oxford American Dictionary , Webster's New World Dictionary , and Lexico from Oxford University Press do not acknowledge such a sense. Most of
10032-836: The language to changing circumstances. In this view, the modern practice is just the "proper" English of the current generation of speakers, much like the earlier abbreviation of corporation names on ticker tape or newspapers. Exact pronunciation of "word acronyms" (those pronounced as words rather than sounded out as individual letters) often vary by speaker population. These may be regional, occupational, or generational differences, or simply personal preference. For instance, there have been decades of online debate about how to pronounce GIF ( / ɡ ɪ f / or / dʒ ɪ f / ) and BIOS ( / ˈ b aɪ oʊ s / , / ˈ b aɪ oʊ z / , or / ˈ b aɪ ɒ s / ). Similarly, some letter-by-letter initialisms may become word acronyms over time, especially in combining forms: IP for Internet Protocol
10146-515: The leader sequence. Multiple CRISPRs contain many spacers to the same phage. The mechanism that causes this phenomenon was discovered in the type I-E system of E. coli . A significant enhancement in spacer acquisition was detected where spacers already target the phage, even mismatches to the protospacer. This 'priming' requires the Cas proteins involved in both acquisition and interference to interact with each other. Newly acquired spacers that result from
10260-403: The leader sequence. Analysis of the type I-E system from E. coli demonstrated that the first direct repeat adjacent to the leader sequence is copied, with the newly acquired spacer inserted between the first and second direct repeats. The PAM sequence appears to be important during spacer insertion in type I-E systems. That sequence contains a strongly conserved final nucleotide (nt) adjacent to
10374-649: The metagenomes produced for the Human Microbiome Project . Although most were body-site specific, some within a body site are widely shared among individuals. One of these loci originated from streptococcal species and contained ≈15,000 spacers, 50% of which were unique. Similar to the targeted studies of the oral cavity, some showed little evolution over time. CRISPR evolution was studied in chemostats using S. thermophilus to directly examine spacer acquisition rates. In one week, S. thermophilus strains acquired up to three spacers when challenged with
10488-466: The more general "x" can be used to replace an unspecified number of letters. Examples include "Crxn" for "crystallization" and the series familiar to physicians for history , diagnosis , and treatment ("hx", "dx", "tx"). Terms relating to a command structure may also sometimes use this formatting, for example gold, silver, and bronze levels of command in UK policing being referred to as Gx, Sx, and Bx. There
10602-635: The other biofilm, suggesting a higher phage activity/prevalence in one community than the other. In the oral cavity, a temporal study determined that 7–22% of spacers were shared over 17 months within an individual while less than 2% were shared across individuals. From the same environment, a single strain was tracked using PCR primers specific to its CRISPR system. Broad-level results of spacer presence/absence showed significant diversity. However, this CRISPR added three spacers over 17 months, suggesting that even in an environment with significant CRISPR diversity some loci evolve slowly. CRISPRs were analysed from
10716-425: The other hand, the evolution of the Cas gene machinery that facilitates the system evolves through classic Darwinian evolution. Analysis of CRISPR sequences revealed coevolution of host and viral genomes. The basic model of CRISPR evolution is newly incorporated spacers driving phages to mutate their genomes to avoid the bacterial immune response, creating diversity in both the phage and host populations. To resist
10830-729: The plural of 'pages', or mss. for manuscripts . The most common capitalization scheme seen with acronyms is all-uppercase ( all caps ). Small caps are sometimes used to make the run of capital letters seem less jarring to the reader. For example, the style of some American publications, including the Atlantic Monthly and USA Today , is to use small caps for acronyms longer than three letters; thus "U.S." and " FDR " in normal caps, but " nato " in small caps. The acronyms " AD " and " BC " are often smallcapped as well, as in: "From 4004 bc to ad 525 ". Where an acronym has linguistically taken on an identity as regular word,
10944-412: The priming mechanism are always found on the same strand as the priming spacer. This observation led to the hypothesis that the acquisition machinery slides along the foreign DNA after priming to find a new protospacer. CRISPR-RNA (crRNA), which later guides the Cas nuclease to the target during the interference step, must be generated from the CRISPR sequence. The crRNA is initially transcribed as part of
11058-483: The pronunciation is reflected graphically by the capitalization scheme. However, it conflicts with conventional English usage of first-letter upper-casing as a marker of proper names in many cases; e.g. AIDS stands for acquired immuno-deficiency syndrome which is not a proper name, while Aids is in the style of one. Some style manuals also base the letters' case on their number. The New York Times , for example, keeps "NATO" in all capitals (while several guides in
11172-502: The protein Cas9 . The Cas9 endonuclease is a four-component system that includes two small molecules: crRNA and trans-activating CRISPR RNA (tracrRNA). In 2012, Jennifer Doudna and Emmanuelle Charpentier re-engineered the Cas9 endonuclease into a more manageable two-component system by fusing the two RNA molecules into a " single-guide RNA " that, when combined with Cas9, could find and cut
11286-685: The publication of the 3rd edition of the Oxford English Dictionary added the expansive sense to its entry for acronym and included the 1940 citation. As the Oxford English Dictionary structures the senses in order of chronological development, it now gives the "initialism" sense first. English language usage and style guides which have entries for acronym generally criticize the usage that refers to forms that are not pronounceable words. Fowler's Dictionary of Modern English Usage says that acronym "denotes abbreviations formed from initial letters of other words and pronounced as
11400-478: The recognition sequence, thereby preventing further rounds of cutting. In theory, repeated rounds of DNA cleavage should cause an increased opportunity for the desired genomic editing to occur. A distinctive feature of Cas12a, as compared to Cas9, is that after cutting its target, Cas12a remains bound to the target and then cleaves other ssDNA molecules non-discriminately. This property is called "collateral cleavage" or "trans-cleavage" activity and has been exploited for
11514-455: The same family. Because those sequences were interspaced, Mojica initially called these sequences "short regularly spaced repeats" (SRSR). In 2001, Mojica and Ruud Jansen , who were searching for an additional interrupted repeats, proposed the acronym CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to unify the numerous acronyms used to describe these sequences. In 2002, Tang, et al. showed evidence that CRISPR repeat regions from
11628-470: The sides of railroad cars (e.g., "Richmond, Fredericksburg and Potomac Railroad" → "RF&P"); on the sides of barrels and crates; and on ticker tape and newspaper stock listings (e.g. American Telephone and Telegraph Company → AT&T). Some well-known commercial examples dating from the 1890s through 1920s include " Nabisco " ("National Biscuit Company"), " Esso " (from "S.O.", from " Standard Oil "), and " Sunoco " ("Sun Oil Company"). Another field for
11742-442: The single-stranded flanks of the DNA and catalyses their integration into CRISPR arrays. New spacers are usually added at the beginning of the CRISPR next to the leader sequence creating a chronological record of viral infections. In E. coli a histone like protein called integration host factor ( IHF ), which binds to the leader sequence, is responsible for the accuracy of this integration. IHF also enhances integration efficiency in
11856-437: The strains' phylogenetic relationships to be determined. A comparative genomic analysis showed that E. coli and S. enterica evolve much more slowly than S. thermophilus . The latter's strains that diverged 250,000 years ago still contained the same spacer complement. Metagenomic analysis of two acid-mine-drainage biofilms showed that one of the analyzed CRISPRs contained extensive deletions and spacer additions versus
11970-604: The target and then cleaves other ssRNA molecules non-discriminately. This collateral cleavage property has been exploited for the development of various diagnostic technologies. In 2021, Dr. Hui Yang characterized novel miniature Cas13 protein (mCas13) variants, Cas13X and Cas13Y. Using a small portion of N gene sequence from SARS-CoV-2 as a target in characterization of mCas13, revealed the sensitivity and specificity of mCas13 coupled with RT-LAMP for detection of SARS-CoV-2 in both synthetic and clinical samples over other available standard tests like RT-qPCR (1 copy/μL). The CRISPR array
12084-476: The term acronym only for forms pronounced as a word, and using initialism or abbreviation for those that are not. Some sources acknowledge the usage, but vary in whether they criticize or forbid it, allow it without comment, or explicitly advocate it. Some mainstream English dictionaries from across the English-speaking world affirm a sense of acronym which does not require being pronounced as
12198-502: The terms as mutually exclusive. Other guides outright deny any legitimacy to the usage: Bryson's Dictionary of Troublesome Words says "Abbreviations that are not pronounced as words (IBM, ABC, NFL) are not acronyms; they are just abbreviations." Garner's Modern American Usage says "An acronym is made from the first letters or parts of a compound term. It's read or spoken as a single word, not letter by letter." The New York Times Manual of Style and Usage says "Unless pronounced as
12312-570: The twenty-first century. The trend among dictionary editors appears to be towards including a sense defining acronym as initialism : the Merriam-Webster's Collegiate Dictionary added such a sense in its 11th edition in 2003, and both the Oxford English Dictionary and The American Heritage Dictionary added such senses in their 2011 editions. The 1989 edition of the Oxford English Dictionary only included
12426-583: The type I-F system of Pectobacterium atrosepticum . but in other systems, different host factors may be required Bioinformatic analysis of regions of phage genomes that were excised as spacers (termed protospacers) revealed that they were not randomly selected but instead were found adjacent to short (3–5 bp) DNA sequences termed protospacer adjacent motifs (PAM). Analysis of CRISPR-Cas systems showed PAMs to be important for type I and type II, but not type III systems during acquisition. In type I and type II systems, protospacers are excised at positions adjacent to
12540-536: The whole range of linguistic registers is relatively new in most languages, becoming increasingly evident since the mid-twentieth century. As literacy spread and technology produced a constant stream of new and complex terms, abbreviations became increasingly convenient. The Oxford English Dictionary ( OED ) records the first printed use of the word initialism as occurring in 1899, but it did not come into general use until 1965, well after acronym had become common. In English, acronyms pronounced as words may be
12654-425: The word " an achro nym ", which is a type of misnomer. Words derived from an acronym by affixing are typically expressed in mixed case, so the root acronym is clear. For example, "pre-WWII politics", "post-NATO world", " DNase ". In some cases a derived acronym may also be expressed in mixed case. For example, " messenger RNA " and " transfer RNA " become "mRNA" and "tRNA". Some publications choose to capitalize only
12768-511: Was done with a full space between every full word (e.g. A. D. , i. e. , and e. g. for " Anno Domini ", " id est ", and " exempli gratia "). This even included punctuation after both Roman and Arabic numerals to indicate their use in place of the full names of each number (e.g. LII. or 52. in place of "fifty-two" and "1/4." or "1./4." to indicate "one-fourth"). Both conventions have fallen out of common use in all dialects of English, except in places where an Arabic decimal includes
12882-534: Was guided by various mechanisms, such as duplication events. On the other hand, each type of class 2 effector module arose from subsequent independent insertions of mobile genetic elements. These mobile genetic elements took the place of the multiple gene effector modules to create single gene effector modules that produce large proteins which perform all the necessary tasks of the effector module. The spacer regions of CRISPR-Cas systems are taken directly from foreign mobile genetic elements and thus their long-term evolution
12996-449: Was little to no naming , conscious attention, or systematic analysis until relatively recent times. Like retronymy, it became much more common in the twentieth century than it had formerly been. Ancient examples of acronymy (before the term "acronym" was invented) include the following: During the mid- to late nineteenth century, acronyms became a trend among American and European businessmen: abbreviating corporation names, such as on
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