Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living things. All known cellular life and some viruses contain DNA. The main role of DNA in the cell is the long-term storage of information. It is often compared to a blueprint, since it contains the instructions to construct other components of the cell, such as proteins and RNA molecules. The DNA segments that carry genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the expression of genetic information.
In eukaryotes such as animals and plants, DNA is stored inside the cell nucleus, while in prokaryotes such as bacteria and archaea, the DNA is in the cell's cytoplasm. Unlike enzymes, DNA does not act directly on other molecules; rather, various enzymes act on DNA and copy its information into either more DNA, in DNA replication, or transcribe it into protein. Other proteins such as histones are involved in the packaging of DNA or repairing the damage to DNA that causes mutations.
The structure of part of a DNA double helix.DNA is a long polymer of simple units called nucleotides, which are held together by a backbone made of sugars and phosphate groups. This backbone carries four types of molecules called bases and it is the sequence of these four bases that encodes information. The major function of DNA is to encode the sequence of amino acid residues in proteins, using the genetic code. To read the genetic code, cells make a copy of a stretch of DNA in the nucleic acid RNA. These RNA copies can then used to direct protein synthesis, but they can also be used directly as parts of ribosomes or spliceosomes.
[edit] Physical and chemical properties
The two strands of DNA are held together by hydrogen bonds between bases. The sugars in the backbone are shown in light blue.DNA is a long polymer made from repeating units called nucleotides. The DNA chain is 22 to 24 angstroms wide and one nucleotide unit is 3.3 angstroms long.[1] Although these repeating units are very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human chromosome is 220 million base pairs long.[2]
In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules. These two long strands entwine like vines, in the shape of a double helix (see the illustration above). The nucleotide repeats contain both the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. In general, a base linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. If multiple nucleotides are linked together, as in DNA, this polymer is referred to as a polynucleotide.
The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is the pentose (five carbon) sugar 2-deoxyribose. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms in the sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand. This arrangement of DNA strands is called antiparallel. The asymmetric ends of a strand of DNA bases are referred to as the 5' (five prime) and 3' (three prime) ends. One of the major differences between DNA and RNA is the sugar, with 2-deoxyribose being replaced by the alternative pentose sugar ribose in RNA.
The DNA double helix is held together by hydrogen bonds between the bases attached to the two strands.[3] The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T).[3] These four bases are shown below and are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.
Adenine Guanine Thymine Cytosine Adenosine monophosphate
Structures of the four bases found in DNA and the nucleotide adenosine monophosphate.These bases are classified into two types, adenine and guanine are fused five and six-membered heterocyclic compounds called purines, while cytosine and thymine are six-membered rings called pyrimidines. A fifth pyrimidine base called uracil (U), replaces thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is normally only found in DNA as a breakdown product of cytosine, but a very rare exception to this rule is a bacterial virus called PBS1 that contains uracil in its DNA.[4]
Structure of a section of DNA. The bases lie horizontally between the two spiralling strands.The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove is 22 angstroms wide and the other 12 angstroms wide.[5] The larger groove is called the major groove, while the smaller, narrower groove is called the minor groove. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually read the sequence by making contacts to the sides of the bases exposed in the major groove.[6]
A GC base pair with three hydrogen bonds (shown as dashed lines).
An AT base pair with two hydrogen bonds (shown as dashed lines).
[edit] Base pairing
Further information: Base pair
Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides joined together across the double helix is called a base pair. In a double helix, the two strands are also held together by forces generated by the hydrophobic effect and pi stacking, but these forces are not affected by the sequence of the DNA.[7] As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.
The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). The GC base-pair is therefore stronger than the AT base pair. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have strongly interacting strands, while short helices with high AT content have weakly interacting strands. Parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in bacterial promoters, tend to have sequences with a high AT content, making the strands easier to pull apart.[8] In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single shape, but some conformations are more stable than others.[9]
[edit] Sense and antisense
Further information: Sense (molecular biology)
DNA is copied into RNA by RNA polymerase enzymes that only work in the 5' to 3' direction.[10] A DNA sequence is called "sense" if its sequence is copied by these enzymes and then translated into protein. The sequence on the opposite strand is complementary to the sense sequence and is therefore called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA. In both prokaryotes and eukaryotes, antisense sequences are transcribed, but the functions of these RNAs are not entirely clear.[11] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.[12]
A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction made above between sense and antisense strands by having overlapping genes.[13] In these cases, some DNA sequences do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction (still 5' to 3') along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription.[14] While in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.[15] Another way of reducing genome size is seen in some viruses that contain linear or circular single-stranded DNA as their genetic material.[16][17]
[edit] Supercoiling
Further information: DNA supercoil
DNA can be twisted like a rope in a process called DNA supercoiling. Normally, with DNA in its "relaxed" state a strand circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.[18] If the DNA is twisted in the direction of the helix this is positive supercoiling and the bases are held more tightly together. If they are twisted in the opposite direction this is negative supercoiling and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.[19] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[20]
From left to right, the structures of A, B and Z DNA.
[edit] Alternative double-helical structures
Further information: Mechanical properties of DNA
The DNA helix can assume one of three slightly different geometries, called the A, B and Z forms. Which conformation DNA adopts depends on the sequence of the DNA, the amount and direction of supercoiling,[21] chemical modifications of the bases and also solution conditions, such as the concentration of metal ions and polyamines.[22] Of these three conformations, the "B" form described above is most common under the conditions found in cells. The two alternative double-helical forms of DNA differ in their geometry and dimensions.
The A form is a wider right-handed spiral, with a shallow and wide minor groove and a narrower and deeper major groove. The A form occurs in dehydrated samples of DNA, such as those used in x-ray crystallography experiments, and possibly in hybrid pairings of DNA and RNA strands.[23] Segments of DNA where the bases have been methylated may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, a mirror image of the more common B form.[24]
Structure of a DNA quadruplex formed by telomere repeats. Image created from NDB UD0017.
[edit] Quadruplex structures
At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as normal DNA polymerases working on the lagging strand cannot copy the extreme 3' ends of their DNA templates.[25] If a chromosome lacked telomeres it would become shorter each time it was replicated. These specialized chromosome caps also help protect the DNA ends from exonucleases and stop the DNA repair systems in the cell from treating them as damage to be corrected.[26] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.[27]
These guanine-rich sequences may stabilise chromosome ends by forming very unusual quadruplex structures. Here, four guanine bases form a flat plate, through hydrogen bonding, and these flat four-base units then stack on top of each other, to form a stable quadruplex.[28] These structures are often stabilized by chelation of a metal ion in the center of each four-base unit. The structure shown to the left is of a quadruplex formed by a DNA sequence containing four consecutive human telomere repeats. The single DNA strand forms a loop, with the sets of four bases stacking in a central quadruplex three plates deep. In the space at the center of the stacked bases are three chelated potassium ions.[29] Other structures can also be formed and the central set of four bases can come from either one folded strand, or several different parallel strands.
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a circle stabilized by telomere-binding proteins.[30] The very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.[28]
[edit] Chemical modifications
[edit] Regulatory base modifications
Further information: DNA methylation
The expression of genes is influenced by modifications of the bases in DNA. In humans, the most common base modification is cytosine methylation to produce 5-methylcytosine. This modification reduces the expression of genes and is particularly important in X-chromosome inactivation.[31] The level of methylation varies between organism, with Caenorhabditis elegans appearing to lack cytosine methylation entirely, while vertebrates show much higher levels, with up to 1% of their DNA being 5-methylcytosine.[32] Unfortunately, the spontaneous deamidation of 5-methylcytosine produces thymine and methylated cytosines are therefore mutation hotspots.[33] Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[34][35]
[edit] DNA damage
Further information: Mutation
Benzopyrene, the major mutagen in tobacco smoke, in an adduct to DNA. Produced from PDB 1JDG.DNA can be damaged many different sorts of mutagens. These include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and x-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light mostly damages DNA by producing pyrimidine dimers, which are cross-links between adjacent pyrimidine bases in a DNA strand.[36] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, as well as double-strand breaks.[37] It has been estimated that about 500 bases suffer oxidative damage, per cell per day.[38][39] Of these oxidative lesions, the most damaging are double-strand breaks, as they can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.[40]
Many mutagens intercalate into the space between two adjacent base pairs. These molecules are mostly polycyclic, aromatic, and planar molecules and include ethidium, proflavin, daunomycin, doxorubicin and thalidomide. DNA intercalators are used in chemotherapeutic treatment of concern to inhibit DNA replication in rapidly growing cancer cells.[41] In order for an intercalator to fit between base pairs, the bases must separate by over 0.3 nanometres, distorting the DNA strand by unwinding of the double helix. These structural modifications often inhibit transcription and replication processes, which makes intercalators potent mutagens. DNA intercalators are often carcinogenic, such as benzopyrene diol epoxide, acridines, aflatoxin and ethidium bromide.[42][43]
[edit] Overview of biological functions
DNA contains the genetic information that allows living things to function, grow and reproduce. This information is held in the sequence of pieces of DNA called genes. Genetic information in genes is transmitted through complementary base pairing. For example, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence in a process called transcription. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles, here we focus on the interactions that happen in these processes between DNA and other molecules.
[edit] Transcription and translation
T7 RNA polymerase producing a mRNA (green) from a DNA template (red and blue). The protein is shown as a purple ribbon. Image derived from PDB 1MSW.Further information: Genetic code, Transcription (genetics), Protein biosynthesis
A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence which then defines a protein sequence. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' (called codons) formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. There are 64 possible codons (4 bases in 3 places 43) that encode 20 amino acids. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region, these are the UAA, UGA and UAG codons.
DNA replication
[edit] Replication
Main article: DNA replication
Cell division is essential for an organism to grow, but when a cell divides it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. All such DNA polymerases extend a DNA strand in a 5 prime to 3 prime direction.[44] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with an perfect copy of its DNA.
[edit] Genes and genomes
[edit] Location and organisation of DNA in cells
Further information: Cell nucleus, Chromatin
DNA is located in the cell nucleus of eukaryotes, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.[45] The DNA is usually in linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. In the human genome, there is approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[46]
[edit] Non-coding DNA in chromosomes
Main article: Non-coding DNA
In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons. The function of the rest is unclear. It is known that certain nucleotide sequences have affinity for DNA binding proteins, which are vital in the control of DNA replication and transcription. These sequences are called regulatory sequences, and researchers believe that so far they have identified only a fraction of the total that exist. "Junk DNA" represents sequences that do not yet appear to have a function. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size ("C-value") among species represent a long-standing puzzle known as the "C-value enigma".
Some DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few (if any) genes, but are important for the function and stability of chromosomes. Some non-coding DNA represents pseudogenes, which have been hypothesized to serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence. Some non-coding DNA provided hot-spots for duplication of short DNA regions.
[edit] Interactions with proteins
All the functions of DNA depend on interactions with proteins. These protein interactions can either be non-specific, or the protein can only bind to a particular DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.
[edit] DNA-binding proteins
Interaction of DNA with histones (shown in white, top). These proteins' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes between DNA and structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[47] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.[48] Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[49] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[50] Other non-specific DNA-binding proteins found in chromatin include the high-mobility group proteins, which bind preferentially to bent or distorted DNA.[51] These proteins are important in bending arrays of nucleosomes and arranging them into more complex chromatin structures.[52]
A distinct group of DNA binding proteins are the single-stranded DNA binding proteins. Unlike molecules such as histones, this class of proteins will only bind to single-stranded DNA. In humans replication protein A is the best-characterised member of this family and is essential for most processes where the double helix is separated, including DNA replication, recombination and DNA repair.[53] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem loops or being degraded by nucleases.
The lambda repressor helix-turn-helix transcription factor bound to its DNA target. Produced from PDB 1LMB.In contrast, other proteins have evolved to specifically bind particular DNA sequences. The most intensively studied of these are the various classes of transcription factors. These proteins control gene transcription. Each one of these proteins bind to one particular set of DNA sequences and thereby activates or inhibits the transcription of genes with these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins, this locates the polymerase at the promoter and allows it to begin transcription.[54] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter, this will change the accessibility of the DNA template to the polymerase.[55]
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[56] Consequently, these proteins are often the targets of the signal transduction processes that mediate responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base interactions are made in the major groove, where the bases are most accessible.[57]
The restriction enzyme EcoRV (green) in a complex with its substrate DNA. Created from PDB 1RVA.
[edit] DNA-modifying enzymes
[edit] Nucleases and ligases
Nucleases are enzymes that can cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while those that cut within strands are called endonucleases. The most frequently-used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5'-GAT|ATC-3' and makes a cut at the vertical line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.
Enzymes also exist that rejoin cut or broken DNA strands, these are called DNA ligases. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template.
[edit] Topioisomerases
An interesting class of enzymes are the DNA topoisomerases, which are enzymes with both nuclease and ligase activity. These proteins act to change the amount of supercoiling in DNA. One way in which these enzyme act is to cut the DNA helix, allow one end to rotate, thereby reducing its torsion strain and supercoiling, and then rejoin the two strands. These enzymes are required for many processes involving DNA, such as DNA replication and transcription.
[edit] Recombination with other DNA molecules
Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).
Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow. Produced from PDB 1M6GA DNA helix does not usually interact with other segments of DNA and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[58] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is when they recombine. Recombination is when two DNA helices break, swap a section and then rejoin. In eukaryotes this process usually occurs during meiosis, when the two sister chromatids are paired together in the center of the cell. Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of selection and can be important in the rapid evolution of new proteins.[59]
The most common form of recombination homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as Cre recombinase. In the first step, the recombinase creates a nick in one strand of a DNA double helix, allowing the nicked strand to pull apart from its complementary strand and anneal to one strand of the double helix on the opposite chromatid. A second nick allows the strand in the second chromatid to pull apart and anneal to the remaining strand in the first helix, forming a structure known as a cross-strand exchange or a Holliday junction. The Holliday junction is a tetrahedral junction structure which can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.
[edit] Use of DNA in technology and industry
[edit] Forensics
Main article: Genetic fingerprinting
Forensic scientists can use DNA located in blood, semen, skin, saliva or hair left at the scene of a crime to identify a possible suspect, a process called genetic fingerprinting or DNA profiling. In DNA profiling the relative lengths of sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys of the University of Leicester, and was first used to convict Colin Pitchfork in 1988 in the Enderby murders case in Leicestershire, United Kingdom. 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.
[edit] Bioinformatics
Main article: Bioinformatics
The unique problems associated with manipulating, searching, and data mining DNA sequence data fall under the purview of bioinformatics. The unique difficulties associated with storing and searching DNA sequences have led to specific advances in computer science, especially string searching algorithms and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was motivated in part by DNA research, where it is used to find specific sequences of nucleotides in a large sequence.[60] In other applications such as text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behavior due to their small number of distinct characters. The related problem of sequence alignment aims to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, can aid in isolating the origins of distinct genetic effects and help in establishing phylogenetic relationships between organisms or lineages.
Publicly available databases have been established for the storage of genetic and genomic data. For example, the database GenBank is searchable using the algorithm BLAST and provides public access to the data generated by thousands of individual sequencing studies, including the known sequences in the human genome.
[edit] DNA and computation
Main article: DNA computing
In 1994, Leonard Adleman of the University of Southern California made headlines when he discovered a way of solving the directed Hamiltonian path problem, an NP-complete problem, using tools from molecular biology, in particular DNA. The new approach, dubbed DNA computing, has practical advantages over traditional computers in power use, space use, and efficiency, due to its ability to highly parallelize the computation (see parallel computing), although there is labor worth mentioning involved in retrieving the answers. A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the Post correspondence problem, have since been analyzed using DNA computing.
Due to its compactness, DNA also has a theoretical role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used.[61]
[edit] History and anthropology
Because DNA collects mutations over time, which are then passed down from parent to offspring, it contains information about processes that have occurred in the past, becoming in time ancient DNA. By comparing different DNA sequences, geneticists can attempt to infer the history of organisms.
If DNA sequences from different species are compared, then the resulting family tree, or phylogeny can be used to study the evolution of these species. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can glean information on the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology (for example, DNA evidence is also being used to try to identify the Ten Lost Tribes of Israel).[62][63]
DNA has also been used to look at fairly recent issues of family relationships, such as establishing some manner of familial relationship between the descendants of Sally Hemings and the family of Thomas Jefferson. This usage is closely related to the use of DNA in criminal investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has fortuitously matched relatives of the guilty individual.[64][65]
[edit] History
James Watson in the Cavendish Laboratory at the University of CambridgeFurther information: History of molecular biology
DNA was first isolated in Germany by Friedrich Miescher (1844-1895), who discovered a substance he called "nuclein" in 1869. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in 1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist only in the chromosomes. This discovery was followed in 1929 Phoebus Levene who identified the base, sugar and phosphate nucleotide unit as the basic component of DNA. He suggested the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns from DNA. He was not able to propose the correct structure but the patterns showed that DNA had a regular structure and therefore it might be possible to deduce what this structure was.
In 1943, Oswald Theodore Avery and a team of scientists discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria merely by mixing killed "smooth" bacteria with live "rough" (R) form. Avery identified DNA as this transforming principle. The role of DNA in hereditary was confirmed in 1953, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed, that DNA is is the genetic material of the T2 phage.
Using X-ray diffraction data from Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick arrived at the first accurate model of DNA's molecular structure in 1953.[66] Watson and Crick proposed the central dogma of molecular biology in 1957, describing the process whereby proteins are produced from nucleic DNA. In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize for their determination of the structure of DNA.
Watson and Crick's model attracted great interest immediately upon its presentation. Arriving at their conclusion on February 21, 1953, Watson and Crick made their first announcement on February 28. In an influential presentation in 1957, Crick laid out the "Central Dogma", 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 1958 in the form of the Meselson-Stahl experiment. Work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, and Har Gobind Khorana and others deciphered the genetic code not long afterward. These findings represent the birth of molecular biology
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answer #9
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answered by wierdos!!! 4
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