Study About DNA: 2010

DNA (DEOXYRIBOSE NUCLEIC ACID)

DNA strand is made from alternating phospate and sugar residues. Thesre two strands run in opposite directions to each other and therfore antiparallel Attached to each sugar is one of four types of molecules called bases. The sugar in DNA is 2 - deoxyribose which is apentose sugar searches of DNA into the related nuclear acid RNA in aproesss sugsrs are joinrd to phospate groups that from phosphodiester bonds btwn the third and4th carbon atoms adjacent sugar rings.

DNA is a long polymer made from repeating units called nucleotides. The DNA is chain is 20 - 26 angstroms wide. DNA polymers can be very large moleculars containing millions of nucleotides chemically with backbones made of sugars and phospates groups joined by ester bonds these onformation is using the genetic code. Phospate groups are joined by ester bonds. In living organisms.

DNA does not usually exist as a single molecule but it exists as a pair of molecules that are held tightly together. These two long strands and entwine like vines in the shape a double helix. which holds chain together and a base which interacts with the other DNA strand in the helix. A base linked to a sugar is nucleiotide. If muultiple nucleiotide are linked to together as in DNA this polymer is known as a polynucleiotide

History of DNA Reseach

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1928, Frederick Griffith discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carried genetic information—the Avery-MacLeod-McCarty experiment—when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed that DNA is the genetic material of the T2 phage.

In 1953 James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases were paired—also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.

Experimental evidence supporting the Watson and Crick model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick mode; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Unfortunately, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the "Central Dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. 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 make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form

DEOXYRIBOSE NUCLEIC ACID

DNA strand is made from alternating phospate and sugar residues. Thesre two strands run in opposite directions to each other and therfore antiparallel Attached to each sugar is one of four types of molecules called bases. The sugar in DNA is 2-deoxyribose which is apentose sugar searches of DNA into the related nuclear acid RNA in aproesss sugsrs are joinrd to phospate groups that from phosphodiester bonds btwn the third and4th carbon atoms adjacent sugar rings.

DNA is a long polymer made from repeating units called nucleotides. The DNA is chain is 20-26 angstroms wide. DNA polymers can be very large moleculars containing millions of nucleotides chemically with backbones made of sugars and phospates groups joined by ester bonds these onformation is using the genetic code. Phospate groups are joined by ester bonds. In living organisms,

DNA does not usually exist as a single molecule but it exists as a pair of molecules that are held tightly together. These two long strands and entwine like vines, in the shape a double helix. which holds chain together and a base which interacts with the other DNA strand in the helix. A base linked to a sugar is nucleiotide. If muultiple nucleiotide are linked to together, as in DNA this polymer is known as a polynucleiotide.

GENETIC DISORDER

Genetic disorder is a condition caused by abnormalities in genes or chromosomes. While some diseases such as cancer. Cancer are due to genetic abnormalities acquired in a few cells during life. The term "genetic disease" most commonly refers to diseases present in all cells of the body and present since conception. Some genetic disorders are caused by chromosomal abnormalities due to errors in meiosis, the process which produces reproductive cells such as sperm and eggs. Examples include Down syndrome, Turner Syndrome and Klinefelter's syndrome. Other genetic changes may occur during the production of germ cells by the parent. One example is the triplet expansion repeat mutations which can cause fragile X syndrome or Huntington's disease. Defective genes may also be inherited intact from the parents. In this case, the genetic disorder is known as a hereditary disease. This can often happen unexpectedly when two healthy carriers of a defective recessive gene reproduce, but can also happen when the defective gene is dominant.

About 4,000 genetic disorders are known with more being discovered. Most disorders are quite rare and affect one person in every several thousands or millions. Cystic fibrosis is one of the most common genetic disorders around 5% of the population of the United States carry at least one copy of the defective gene. Some types of recessive gene disorder confer an advantage in the heterozygous state in certain environments.Genetic diseases are typically diagnosed and treated by geneticists. Genetic counselors assist the physicians and directly counsel patients. The study of genetic diseases is a scientific discipline whose theoretical underpinning is based on population genetics.

MONOCLONAL ANTIBODIES

Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cells.

Given almost any substance. It is possible to create monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the non-proprietary drug name ends in -mab.

Phylogetics DNA

Every living cells contains DNA, RNA and protiens. closely related organisms generally have degree of agreement in the molecular structure of these substances,Heterogenous nuclear ribonucleoprotiens are spliceosomal macromolecular assemblages and thus actively participate in pre-mRNA metabloism.

conserved sequnces. such as mitochondrial DNA are expected to accumalate mutations over time and assuming a constant rate of mutation provide molecular interaction features.

Molecular characterization of human hnRNP A3 showed that while the recombinant hnRNP A3 with its 296 amino acids migrates as excpted as 32 kDA protien on SDS-PAGE analysis, it is recoginzed by the patient's sera as a 50 kda highly related ye unknownv crossreactive protien.

The sequence comparision. however may be insufficient for deduction of its functional role patients diagnozed with the suspected disease. therefore we followed the suggestion of ponting CS and Russel RRSurprisingly, neither the 50 kda nor the 32kda protien was dected in the suspected disease.

RECOMBINANT DNA

Recombinant DNA is a form of artificial DNA that is engineered through the combination of insertion of one or more DNA strands. Therefor combining DNA sequences that would not normally occur together. In terms of genetic modification, recombinant DNA is produced through the addition of relevant DNA into an existing organismal genome, such as the plasmid of bacteria, to code for or alter different traits for a specific purpose, such as immunity. It differs from genetic recombination, in that it does not occur through processes within the cell or ribosome, but is exclusively engineered.The Recombinant DNA technique was engineered by Stanley Norman Cohen and Herbert Boyer in 1973. They published their findings in a 1974 paper entitled "Construction of Biologically Functional Bacterial Plasmids in vitro". Which described a technique to isolate and amplify genes or DNA segments and insert them into another cell with precision, creating a transgenic bacterium.

DNA (Deoxyribonucleic Acid)

Deoxyribonucleic Acid (DNA) is genetic material found in the cells of all living organisms. DNA is the fundamental building blocks for life. Nearly every cell (with a nucleus) in a person's body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but DNA can also found in the mitochondria (where it is called mitochondrial DNA or mtDNA).The information in DNA is made up four bases which combine to form chains. These bases include two purines (Adenine and Guanine) and two pyrimidines (Cytosine and Thymine). These are commonly referred to as A, G, C and T respectively. Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. It is the order, or sequence, of these bases which determines genetic characteristics.

The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder's rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. Each base is attached to a Sugar (S) molecule and Phosphate (P) molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The number of purine bases in DNA is equal to the number of pyrimidines. This is due to the law of complimentary base pairing. which is Thymine (T) can only pair with Adenine (A), and Guanine (G) can only pair with Cytosine (C). Knowing this rule, we could predict the base sequence of one DNA strand if we knew the sequence of bases in the complimentary strand.

DNA is Double Helix

DNA is shown in the double-stranded helical model for the graphic on the left. The easiest way to visualize DNA is an immensely long rope ladder, twisted into a cork-screw shape. The sides of the ladder are alternating sequences of deoxyribose and phosphate (backbone) while the rungs of the ladder (bases) are made in two parts with each part firmly attached to the side of the ladder. The parts in the rung are heterocyclic amines held in position by hydrogen bonding. Although most DNA exists as open ended double helices, some bacterial DNA has been found a cyclic helix. Occasionally, DNA has been found as a single strand.

Forensic DNA Testing

There are two main types of forensic DNA testing. Called, RFLP and PCR based testing, although these terms are not very descriptive. Generally, RFLP testing requires larger amounts of DNA and DNA must be underrated. Crime-scene evidence that is old or that is present in small amounts is often unsuitable for RFLP test. Warm moist conditions may accelerate DNA degradation rendering it unsuitable for RFLP in relatively short period of time.

PCR-based testing often requires less DNA than RFLP testing and the DNA may be partially degraded, more so than is the case with RFLP. However, PCR still has sample size and degradation limitations that sometimes may under-appreciated. PCR-based tests are extremely sensitive to contaminating DNA at the crime scene and within the test laboratory. During PCR, contaminants amplified up to a billion times their original concentration. Contamination can influence PCR results, particularly in the absence of proper handling techniques and proper controls for contamination.PCR are less direct and more prone to error than RFLP. However, PCR has tended to replace RFLP in forensic testing primarily because PCR based tests is faster and more sensitive.

DNA Analysis and Gene Cloning

Known world wide as the standard introductory test to this important and exciting area, the fifth edition of Gene Cloning and DNA Analysis addresses new and growing area of research which retaining the philosophy of the previous edition. Assuming the reader has little prior knowledge of subject is important. The principles of the techniques used and their applications are all carefully laid out. With over 250 clearly presented two color illustrations.

In addition to number of informative changes to the test throughout the book, The final four chapters have been significantly updated and extended to reflect the striking advances made in resent years in the application of gene cloning and DNA analysis in biotechnology.

Extended chapter on agriculture including new material on glyphosate resistant plants, New section of the uses of gene cloning and PCR in archaeology. Coverage of ethical concerns relating to farming, Gene therapy and GM crops, Gen Cloning and DNA Analysis remains and essential industry test to wide range of biological science Students including genetics and genomic, molecular biology, biochemistry, immunology and applied biology. It is perfect industry test for any processional needing to learn to basic of the subjects. All libraries in universalities where medical, life and biological sciences are taught should have copies available their shelves.

MICROARRAYS Applications

DNA Microarray technology helps in the identification of new genes, know about their functioning and expression levels under different conditions. Disease diagnosis:- DNA Microarray technology helps researchers learn more about different diseases such as heart diseases, mental illness, infectious disease and especially the study of cancer. Until recently, different types of cancer have been classified on the basis of the organs in which the tumors develop. Now, with the evolution of microarray technology, it will be possible for the researchers to further classify the types of cancer on the basis of the patterns of gene activity in tumor cells. This will tremendously help the pharmaceutical community to develop more effective drugs as the treatment strategies will be targeted directly to the specific type of cancer.

Drug discovery:- Microarray technology has extensive application in Pharmacogenomics. Pharmacogenomics is the study of correlations between therapeutic responses to drugs and the genetic profiles of the patients. Comparative analysis of the genes from a diseased and normal cell will help the identification of the biochemical constitution of the proteins synthesized by the diseased genes. The researchers can use this information to synthesize drugs which combat with these proteins and reduce their effect.

Toxicological research:- Microarray technology provides a robust platform for the research of the impact of toxins on the cells and their passing on to the progeny. Toxicogenomics establishes correlation between responses to toxicants and changes in the genetic profiles of the cells exposed to such toxicants.

RNA Data Sequences in DNA

Proteins are not the only substances that are synthesized directly from data within the DNA. Some forms of RNA are specialized, and also have their formula encoded directly in digital DNA formulae. Not all types of RNA are temporary intermediate forms with their form depending on whatever DNA they are copying. There are certain forms of RNA that have a particular form that is the same across all individuals. Some of these special-purpose RNA forms are,
1. tRNA - transfer RNA
2. rRNA - ribosome RNA

There are exactly 20 forms of tRNA, one each transfer a particular amino acid. tRNA molecules contain about 75-80 bases. tRNA recognizes one of the 64 triplets, and matches it one of the 20 amino acids. Since there are 20 tRNA types, and not 64, each tRNA molecule has to recognize more than one triplet ordering as a match. The DNA code contains multiple repetitions of codes for tRNA and rRNA. About 280 copies are spread over 5 chromosomes. Presumably, this allows each cell to make multiple copies of tRNA and rRNA molecules at once from its single copy of the DNA.

History of DNA research

Rosalind F

ranklin

Raymond

Gosling

In 1953 James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases were paired—also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.

Experimental evidence supporting the Watson and Crick model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick mode; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Unfortunately, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.
In an influential presentation in 1957, Crick laid out the "Central Dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology

DNA nanotechnology

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling bra

nched DNA complexes with useful properties.[124] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based as well as using the "DNA origami" method) as well as three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.

Bioinformatics

Bioinformatics involves the manipulation, searching, and data mining of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory.[120] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. 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 behaviour 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, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without annotations, which label the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products in an organism even before they have been isolated experimentally.

Forensics

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is called genetic fingerprinting, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents. On the other hand, many convicted people have been released from prison on the basis of DNA techniques, which were not available when a crime had originally been committed.

Genetic engineering

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction and manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, or be grown in agriculture.

DNA-binding proteins

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with 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. 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. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. 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. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosom

es.

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. 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

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have 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. 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.

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. Consequently, these proteins are often the targets of the signal transduction processes that control 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.

Transcription and translation

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 one or more protein sequences. 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. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.

Genes and genomes

Genomic 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. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame.

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, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma." However, DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.
T7 RNA polymerase (blue) producing a mRNA (green) from a DNA template (orange).

Some non-coding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of non-coding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

Biological functions

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[64] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation which depends on the same interaction between RNA nucleotides. 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 between DNA and other molecules that mediate the function of the genome.

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 the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

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 long circle stabilized by telomere-binding proteins. At 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

Alternate DNA structures

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns— and also B-DNA used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then propos

ed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, Watson and Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.

Although the `B-DNA form' is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation 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, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription

Sense and antisense

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

Base pairing

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 binding together across the double helix is called a base pair. 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 rep

lication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.
GC DNA base pair.svg
AT DNA base pair.svg
Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

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, left). DNA with high GC-content is more stable than DNA with low GC-content, but contrary to popular belief, this is not due to the extra hydrogen bond of a GC base pair but rather the contribution of stac

king interactions (hydrogen bonding merely provides specificity of the pairing, not stability). 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 stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart. 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 common shape, but some conformations are more stable than others