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| '''Deoxyribonucleic acid''' ('''DNA''') is a ] which is capable of carrying ] ]s for the ] of all cellular forms of ] and many ]es. DNA is sometimes referred to as the ] of ] as it is ] and used to propagate ]s. During ], it is ] and transmitted to offspring. | |||
| In ] and other ] ] organisms, DNA is not separated from the ] by a ]. In the ] cells that make up ]s, ]s and in other multi-celled ]s, by contrast, most of the DNA is located in the ]. The ]-generating ]s known as ]s and ] also carry DNA, as do many ]es. | |||
| == DNA in brief == | |||
| <!-- | |||
| PLEASE, PLEASE try to refrain from transforming this section into another highly-accurate-but-impossible-to-read one! It has been assumed from the beginning that this is not necessarily a very accurate description, and that it's only meant as a generic overview. | PLEASE, PLEASE try to refrain from transforming this section into another highly-accurate-but-impossible-to-read one! It has been assumed from the beginning that this is not necessarily a very accurate description, and that it's only meant as a generic overview. | ||
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| ==DNA in crime== | ==DNA in crime== | ||
| ] can use DNA located in blood, semen, or hair left at the scene of a crime to identify a possible suspect, a process called ] or genetic fingerprinting. In DNA profiling the relative lengths of sections of repetitive DNA, such as ] and ] are compared. DNA profiling was developed in ] English geneticist ], and was first used in ] in the ] case in ], England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in ] cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects. | ] can use DNA located in blood, semen, or hair left at the scene of a crime to identify a possible suspect, a process called ] or genetic fingerprinting. In DNA profiling the relative lengths of sections of repetitive DNA, such as ] and ] are compared. DNA profiling was developed in ] English geneticist ], and was first used in ] in the ] case in ], England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in ] cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects. | ||
| == Overview of molecular structure == | |||
| ] structure]] | |||
| Although sometimes called "the molecule of heredity", pieces of DNA as people typically think of them are not single molecules. Rather, they are pairs of molecules, which entwine like vines to form a '''double ]''' (see the illustration at the right). | |||
| Each vine-like molecule is a strand of DNA: a chemically linked chain of ]s, each of which consists of a ], a ] and one of four kinds of ]s ("bases"). Because DNA strands are composed of these nucleotide subunits, they are ]s. | |||
| The diversity of the bases means that there are four kinds of nucleotides, which are commonly referred to by the identity of their bases. These are ] (A), ] (T), ] (C), and ] (G). | |||
| In a DNA double helix, two polynucleotide strands can associate through the ]. Specificity of which strands stay associated is determined by ]. Each base forms ]s readily to only one other -- A to T and C to G -- so that the identity of the base on one strand dictates the strength of the association; the more complementary bases exist, the stronger and longer-lasting the association. | |||
| The cell's machinery is capable of ''melting'' or disassociating a DNA double helix, and using each DNA strand as a template for synthesizing a new strand which is nearly identical to the previous strand. Errors that occur in the synthesis are known as ]. The process known as ] mimics this process '''in vitro''' in a nonliving system. | |||
| Because pairing causes the nucleotide bases to face the helical axis, the sugar and phosphate groups of the nucleotides run along the outside; the two chains they form are sometimes called the "'''backbones'''" of the helix. In fact, it is chemical bonds between the phosphates and the sugars that link one nucleotide to the next in the DNA strand. | |||
| ==The role of the sequence== | |||
| Within a gene, the sequence of nucleotides along a DNA strand defines a ], which an ] is liable to manufacture or "]" at one or several points in its life using the information of the sequence. The relationship between the nucleotide sequence and the ] sequence of the protein is determined by simple cellular rules of ], known collectively as the ]. The genetic code is made up of three-letter 'words' (termed a ]) formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). These codons can then be translated with messenger RNA and then transfer RNA, with a codon corresponding to a particular amino acid. Since there are 64 possible codons, most amino acids have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region. | |||
| In many ] of organism, only a small fraction of the total sequence of the ] appears to encode protein. The function of the rest is a matter of speculation. It is known that certain nucleotide sequences specify affinity for ]s, which play a wide variety of vital roles, in particular through control of replication and transcription. These sequences are frequently called ]s, and researchers assume that so far they have identified only a tiny fraction of the total that exist. "]" represents sequences that do not yet appear to contain genes or to have a function. | |||
| Sequence also determines a DNA segment's susceptibility to cleavage by ]s, the quintessential tools of ]. The position of cleavage sites throughout an individual's genome determines one kind of an individual's "]". | |||
| ==DNA replication== | |||
| ''Main article:'' ] | |||
| <!-- summary has been added, below, also include any extra context relevant for this article as well | |||
| ..]...chromosome...plasmid...DNA polymerase...]... | |||
| --> | |||
| DNA replication or DNA synthesis is the process of copying the double-stranded DNA prior to ]. The two resulting double strands are generally almost perfectly identical, but occasionally errors in replication can result in a less than perfect copy (see ]), and each of them consists of one original and one newly synthesized strand. This is called '']''. The process of replication consists of three steps: ''initiation'', ''replication'' and ''termination''. | |||
| ==Mechanical properties relevant to biology== | |||
| ] | |||
| The hydrogen bonds between the strands of the double helix are weak enough that they can be easily separated by ]s. Enzymes known as ]s unwind the strands to facilitate the advance of sequence-reading enzymes such as ]. The unwinding requires that helicases chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. The strands can also be separated by gentle heating, as used in ], provided they have fewer than about 10,000 '''base pairs''' (10 kilobase pairs, or 10 kbp). The intertwining of the DNA strands makes long segments difficult to separate. | |||
| When the ends of a piece of double-helical DNA are joined so that it forms a circle, as in ] DNA, the strands are ] knotted. This means they cannot be separated by gentle heating or by any process that does not involve breaking a strand. The task of unknotting topologically linked strands of DNA falls to enzymes known as ]s. Some of these enzymes unknot circular DNA by cleaving two strands so that another double-stranded segment can pass through. Unknotting is required for the replication of circular DNA as well as for various types of ] in linear DNA. | |||
| The DNA helix can assume one of three slightly different geometries, of which the "B" form described by ] and ] is believed to predominate in cells. It is 2 ]s wide and extends 3.4 nanometres per 10 ] of sequence. This is also the approximate length of sequence in which the double helix makes one complete turn about its axis. This frequency of twist (known as the helical ''pitch'') depends largely on stacking forces that each base exerts on its neighbors in the chain. | |||
| The narrow breadth of the double helix makes it impossible to detect by conventional ], except by heavy staining. At the same time, the DNA found in many cells can be macroscopic in length -- approximately 5 ]s long for strands in a human chromosome. Consequently, cells must compact or "package" DNA to carry it within them. This is one of the functions of the chromosomes, which contain spool-like ]s known as ]s, around which DNA winds. | |||
| The B form of the DNA helix twists 360° per 10.6 bp in the absence of strain. But many molecular biological processes can induce strain. A DNA segment with excess or insufficient helical twisting is referred to, respectively, as positively or negatively "]". DNA ''in vivo'' is typically negatively supercoiled, which facilitates the unwinding of the double-helix required for ]. | |||
| The two other known double-helical forms of DNA, called A and ], differ modestly in their geometry and dimensions. The A form appears likely to occur only in dehydrated samples of DNA, such as those used in ] experiments, and possibly in hybrid pairings of DNA and ] strands. Segments of DNA that cells have ] for regulatory purposes may adopt the Z geometry, in which the strands turn about the helical axis like a mirror image of the B form. | |||
| Other, including non-helical, forms of DNA have been described, for example a side-by-side (SBS) configuration. Indeed, it is far from certain that the B-form double helix is the dominant form in living cells. | |||
| ===Comparison geometries of some DNA forms=== | |||
| {| border="0" align="center" style="border: 1px solid #999; background-color:#FFFFFF" | |||
| |-align="center" bgcolor="#CCCCCC" | |||
| !Geometry attribute | |||
| !A-form | |||
| !B-form | |||
| !Z-form | |||
| |- | |||
| |Helix sense ||align="center"| right-handed ||align="center"| right-handed ||align="center"| left-handed | |||
| |--bgcolor="#EFEFEF" | |||
| |Repeating unit ||align="right"| 1 bp ||align="right"| 1 bp ||align="right"| 2 bp | |||
| |----- | |||
| |Rotation/bp ||align="right"| 33.6° ||align="right"| 35.9° ||align="right"| 60°/2 | |||
| |--bgcolor="#EFEFEF" | |||
| |Mean bp/turn ||align="right"| 10.7 ||align="right"| 10.0 ||align="right"| 12 | |||
| |----- | |||
| |Inclination of bp to axis ||align="right"| +19° ||align="right"| -1.2° ||align="right"| -9° | |||
| |--bgcolor="#EFEFEF" | |||
| |Rise/bp along axis ||align="right"| 2.3Å ||align="right"| 3.32Å ||align="right"| 3.8Å | |||
| |----- | |||
| |Pitch/turn of helix ||align="right"| 24.6Å ||align="right"| 33.2Å ||align="right"| 45.6Å | |||
| |--bgcolor="#EFEFEF" | |||
| |Mean propeller twist ||align="right"| +18° ||align="right"| +16° ||align="right"| 0° | |||
| |----- | |||
| |Glycosyl angle ||align="center"| anti ||align="center"| anti ||align="center"| C: anti,<br> G: syn | |||
| |--bgcolor="#EFEFEF" | |||
| |Sugar pucker ||align="center"| C3'-endo ||align="center"| C2'-endo ||align="center"| C: C2'-endo,<br>G: C2'-exo | |||
| |----- | |||
| |Diameter ||align="right"| 26Å ||align="right"| 20Å ||align="right"| 18Å | |||
| |--bgcolor="#EFEFEF" | |||
| |} | |||
| ==DNA sequence reading== | |||
| The asymmetric shape and linkage of nucleotides means that a DNA strand always has a discernible orientation or directionality. Because of this directionality, close inspection of a double helix reveals that nucleotides are heading one way along one strand (the "''ascending strand''"), and the other way along the other strand (the "''descending strand''"). This arrangement of the strands is called '''antiparallel'''. | |||
| For reasons of chemical nomenclature, people who work with DNA refer to the asymmetric termini of each strand as the '''5'''' and '''3'''' ends (pronounced "five prime" and "three prime"). DNA workers and enzymes alike always read nucleotide sequences in the "'''5' to 3' direction'''". In a vertically oriented double helix, the 3' strand is said to be ascending while the 5' strand is said to be descending. | |||
| As a result of their antiparallel arrangement and the sequence-reading preferences of enzymes, even if both strands carried identical instead of complementary sequences, cells could properly translate only one of them. The other strand a cell can only read backwards. ] call a sequence "'''sense'''" if it is translated or translatable, and they call its complement "'''antisense'''". It follows then, somewhat paradoxically, that the template for transcription is the ''antisense'' strand. The resulting transcript is an RNA replica of the ''sense'' strand and is itself ''sense.'' | |||
| Some viruses blur the distinction between sense and antisense, because certain sequences of their ] do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction along the other strand. As a result, the genomes of these viruses are unusually compact for the number of genes they contain, which biologists view as an ]. | |||
| Topologists like to note that the juxtaposition of the 3' end of one DNA strand beside the 5' end of the other at both termini of a double-helical segment makes the arrangement a "]". | |||
| ==Single-stranded DNA (ssDNA) and repair of mutations== | |||
| In some ]es DNA appears in a non-helical, single-stranded form. Because many of the ] mechanisms of cells work only on paired bases, viruses that carry single-stranded DNA ]s ] more frequently than they would otherwise. As a result, such species may adapt more rapidly to avoid extinction. The result would not be so favorable in more complicated and more slowly replicating organisms, however, which may explain why only viruses carry single-stranded DNA. These viruses presumably also benefit from the lower cost of replicating one strand versus two. | |||
| ==The discovery of DNA and the double helix== | |||
| ] in the ] at the ]]] | |||
| Working in the ], biochemists initially isolated DNA and RNA (mixed together) from cell nuclei. They were relatively quick to appreciate the polymeric nature of their "nucleic acid" isolates, but realized only later that nucleotides were of two types--one containing ] and the other ]. It was this subsequent discovery that led to the identification and naming of DNA as a substance distinct from RNA. | |||
| ] (]-]) discovered a substance he called "nuclein" in ]. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in ] his pupil, ], named it "nucleic acid". This substance was found to exist only in the chromosomes. | |||
| ], ], and ] published results in ] suggesting that chromosomes are very large molecules the structure of which can be changed by treatment with ]s, and that by so changing their structure it was possible to change the heritable characteristics governed by those chromosomes. (Delbrück and ] were awarded the ] in ] for their work on the genetic structure of viruses.) In ], ] discovered that traits proper to the "smooth" form of the ''Pneumococcus'' could be transferred to the "rough" form of the same bacteria merely by making the killed "smooth" (S) form available to the live "rough" (R) form. Quite unexpectedly, the living R ''Pneumococcus'' bacteria were transformed into a new strain of the S form, and the transferred S characteristics turned out to be heritable. | |||
| ]'s first sketch of the ] double-helix pattern]] | |||
| In ], the renowned physicist, ], published a brief book entitled ''What is Life?'', where he maintained that chromosomes contained what he called the "hereditary code-script" of life. He added: "But the term code-script is, of course, too narrow. The chromosome structures are at the same time instrumental in bringing about the development they foreshadow. They are law-code and executive power -- or, to use another simile, they are architect's plan and builder's craft -- in one." He conceived of these dual functional elements as being woven into the molecular structure of chromosomes. By understanding the exact molecular structure of the chromosomes one could hope to understand both the "architect's plan" and also how that plan was carried out through the "builder's craft." ], ], ], ], ], et al., took up the physicist's challenge to work out the structure of the chromosomes and the question of how the segments of the chromosomes that were conceived to relate to specific traits could possibly do their jobs. | |||
| Just how the presence of specific features in the molecular structure of chromosomes could produce traits and behaviors in living organisms was unimaginable at the time. Because chemical dissection of DNA samples always yielded the same four nucleotides, the chemical composition of DNA appeared simple, perhaps even uniform. Organisms, on the other hand, are fantastically complex individually and widely diverse collectively. Geneticists did not speak of genes as conveyors of "information" in such words, but if they had, they would not have hesitated to quantify the amount of information that genes need to convey as vast. The idea that information might reside in a chemical in the same way that it exists in text--as a finite alphabet of letters arranged in a sequence of unlimited length--had not yet been conceived. It would emerge upon the discovery of DNA's structure, but few researchers imagined that DNA's structure had much to say about genetics. | |||
| ] in London.]] | |||
| In the ], only a few groups made it their goal to determine the structure of DNA. These included an American group led by ], and two groups in Britain. At the ], Crick and Watson were building physical models using metal rods and balls, in which they incorporated the known chemical structures of the nucleotides, as well as the known position of the linkages joining one nucleotide to the next along the polymer. At ], ] and ] were examining ] patterns of DNA fibers. | |||
| A key inspiration in the work of all of these teams was the discovery in ] by Pauling that many proteins included helical (see ]) shapes. Pauling had deduced this structure from X-ray patterns. Even in the initial crude diffraction data from DNA, it was evident that the structure involved helices. But this insight was only a beginning. There remained the questions of how many strands came together, whether this number was the same for every helix, whether the bases pointed toward the helical axis or away, and ultimately what were the explicit angles and coordinates of all the bonds and atoms. Such questions motivated the modeling efforts of Watson and Crick. | |||
| In their modeling, Watson and Crick restricted themselves to what they saw as chemically and biologically reasonable. Still, the breadth of possibilities was very wide. A breakthrough occurred in ], when ] visited Cambridge and inspired Crick with a description of experiments Chargaff had published in ]. Chargaff had observed that the proportions of the four nucleotides vary between one DNA sample and the next, but that for particular pairs of nucleotides -- adenine and thymine, guanine and cytosine -- the two nucleotides are always present in equal proportions. | |||
| Watson and Crick had begun to contemplate double helical arrangements, and they saw that by reversing the directionality of one strand with respect to the other, they could provide an explanation for Chargaff's puzzling finding. This explanation was the complementary pairing of the bases, which also had the effect of ensuring that the distance between the phosphate chains did not vary along a sequence. Watson and Crick were able to discern that this distance was constant and to measure its exact value of 2 nanometres from an X-ray pattern obtained by Franklin. The same pattern also gave them the 3.4 nanometre-per-10 bp "]" of the helix. The pair quickly converged upon a model, which they announced before Franklin herself published any of her work. | |||
| ] | |||
| The great assistance Watson and Crick derived from Franklin's data has become a subject of controversy, and it has angered people who believe Franklin has not received the credit due to her. The most controversial aspect is that Franklin's critical X-ray pattern was shown to Watson and Crick without Franklin's knowledge or permission. Wilkins showed it to them at his lab while Franklin was away. | |||
| Watson and Crick's model attracted great interest immediately upon its presentation. Arriving at their conclusion on ] ], Watson and Crick made their first announcement on ]. Their paper was published on ]. In an influential presentation in ], Crick laid out the "]", which foretold the relationship between DNA, RNA, and proteins, and articulated the "sequence hypothesis." A critical confirmation of the replication mechanism that was implied by the double-helical structure followed in ] in the form of the ]. Work by Crick and coworkers deciphered the ] not long afterward. These findings represent the birth of ]. | |||
| ], ], and ] were awarded the ] ] for discovering the molecular structure of DNA, by which time ] had died. Nobel prizes are not awarded posthumously. | |||
| ==Bibliography== | |||
| * ''DNA: The Secret of Life'', by James D. Watson. ISBN 0-375-41546-7 | |||
| ==External links== | |||
| * | |||
| *]: | |||
| * | |||
| *Watson, James, and Francis Crick, "'', A structure for Deoxyribose Nucleic Acid''". April 2, 1953. (paper on the structure of DNA) | |||
| * (requires ]) | |||
| * | |||
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Revision as of 22:56, 12 April 2005
PLEASE, PLEASE try to refrain from transforming this section into another highly-accurate-but-impossible-to-read one! It has been assumed from the beginning that this is not necessarily a very accurate description, and that it's only meant as a generic overview.
- Misplaced Pages needs to be accurate, but it can be simple and accurate. Dumbing down something too much (which I'm not saying is happening here) is also to be avoided. --Lexor|Talk
This is what most people need, and that's why it has been inserted at the top of the article. If you find that curious, or even absurd, think how you would feel if some article which pertains to scientific dissection in a field you don't master only contained scientific data -- that would be frustrating, wouldn't it?
Thank you for understanding!
--Gutza 11:47, 5 Oct 2004 (UTC)
//-->
This section presents a brief and simple overview of DNA.
- Genes can be loosely viewed as the organism's "cookbook";
- A strand of DNA contains genes, areas that regulate genes, and areas that either have no function, or a function we do not (yet) know;
- DNA is organized as two complementary strands, head-to-toe, with bonds between them that can be "unzipped" like a zipper, separating the strands;
- DNA is encoded with four interchangeable "building blocks", called "bases", which can be abbreviated A, T, C, and G (adenine, thymine, cytosine, and guanine, respectively); each base "pairs up" with only one other base: A+T, T+A, C+G and G+C; that is, an "A" on one strand of double-stranded DNA will "mate" properly only with a "T" on the other, complementary strand;
- The order does matter: A+T is not the same as T+A, just as C+G is not the same as G+C;
- However, since there are just four possible combinations, naming only one base on the conventionally chosen side of the strand is enough to describe the sequence;
- The order of the bases along the length of the DNA is what it's all about, the sequence itself is the description for genes;
- Replication is performed by splitting (unzipping) the double strand down the middle via relatively trivial chemical reactions, and recreating the "other half" of each new single strand by drowning each half in a "soup" made of the four bases. Since each of the "bases" can only combine with one other base, the base on the old strand dictates which base will be on the new strand. This way, each split half of the strand plus the bases it collects from the soup will ideally end up as a complete replica of the original, unless a mutation occurs;
- Mutations are simply chemical imperfections in this process: a base is accidentally skipped, inserted, or incorrectly copied, or the chain is trimmed, or added to; all other basic mutations can be described as combinations of these accidental "operations".
DNA in crime
Forensic scientists can use DNA located in blood, semen, or hair left at the scene of a crime to identify a possible suspect, a process called DNA profiling or genetic fingerprinting. In DNA profiling the relative lengths of sections of repetitive DNA, such as short tandom repeats and minisatellites are compared. DNA profiling was developed in 1984 English geneticist Alec Jeffries, and was first used in 1986 in the Enderby murders case in Leicestershire, England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in rape cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects.