What is the word for dna

Deoxyribonucleic acid (;^[1] DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides.^[2][3] Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds (known as the phosphodiester linkage) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.

Both strands of double-stranded DNA store the same biological information. This information is replicated when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (or bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U).^[4] Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA.^[5] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Properties

DNA is a long polymer made from repeating units called nucleotides.^[6][7] The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes.^[8] In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of 34 ångströms (3.4 nm). The pair of chains have a radius of 10 Å (1.0 nm).^[9] According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long.^[10]

DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together.^[9][11] These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.^[12]

The backbone of the DNA strand is made from alternating phosphate and sugar groups.^[13] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond.^[11]

Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA.^[11]

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.^[15] The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs.^[16][17]

Nucleobase classification

The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T.^[11] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.^[18]

Non-canonical bases

Modified bases occur in DNA. The first of these recognized was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925.^[19] The reason for the presence of these noncanonical bases in bacterial viruses (bacteriophages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.^[20] Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals.^[21]

A number of noncanonical bases are known to occur in DNA.^[22] Most of these are modifications of the canonical bases plus uracil.

• Modified Adenine
  • N6-carbamoyl-methyladenine
  • N6-methyadenine
• Modified Guanine
  • 7-Deazaguanine
  • 7-Methylguanine
• Modified Cytosine
  • N4-Methylcytosine
  • 5-Carboxylcytosine
  • 5-Formylcytosine
  • 5-Glycosylhydroxymethylcytosine
  • 5-Hydroxycytosine
  • 5-Methylcytosine
• Modified Thymidine
  • α-Glutamythymidine
  • α-Putrescinylthymine
• Uracil and modifications
  • Base J
  • Uracil
  • 5-Dihydroxypentauracil
  • 5-Hydroxymethyldeoxyuracil
• Others
  • Deoxyarchaeosine
  • 2,6-Diaminopurine (2-Aminoadenine)

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found 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 symmetrically located with respect to each other, the grooves are unequally sized. The major groove is 22 ångströms (2.2 nm) wide, while the minor groove is 12 Å (1.2 nm) in width.^[23] Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.^[24] 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 width that would be seen if the DNA was twisted back into the ordinary B form.

Base pairing

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low GC-content. A Hoogsteen base pair (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing.^[25] As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.^[26] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.^[7]

ssDNA vs. dsDNA

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the melting temperature (also called T_m value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have more strongly interacting strands, while short helices with high AT content have more weakly interacting strands.^[27] 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.^[28]

In the laboratory, the strength of this interaction can be measured by finding the melting temperature T_m necessary to break half of the hydrogen bonds. 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.^[29]

Amount

In humans, the total female diploid nuclear genome per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23 cm long and weighs 6.51 picograms (pg).^[30] Male values are 6.27 Gbp, 205.00 cm, 6.41 pg.^[30] Each DNA polymer can contain hundreds of millions of nucleotides, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, and would be 85 mm long if straightened.^[31]

In eukaryotes, in addition to nuclear DNA, there is also mitochondrial DNA (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the human mitochondrial DNA forms closed circular molecules, each of which contains 16,569^[32][33] DNA base pairs,^[34] with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules.^[34] Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.^[34] However, the amount of mitochondria per cell also varies by cell type, and an egg cell can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of the mitochondrial genome (constituting up to 90% of the DNA of the cell).^[35]

Sense and antisense

A DNA sequence is called a «sense» sequence if it is the same as that of a messenger RNA copy that is translated into protein.^[36] 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 can 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.^[37] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.^[38]

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.^[39] 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,^[40] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.^[41]

Supercoiling

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its «relaxed» state, a strand usually 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.^[42] 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.^[43] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.^[44]

Alternative 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.^[13] 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, and the presence of polyamines in solution.^[45]

The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson functions that provided only a limited amount of structural information for oriented fibers of DNA.^[46][47] An alternative analysis was proposed 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.^[48] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.^[9]

Although the B-DNA form is most common under the conditions found in cells,^[49] it is not a well-defined conformation but a family of related DNA conformations^[50] that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.^[51][52]

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 partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.^[53][54] 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.^[55] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.^[56]

Alternative DNA chemistry

For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1 was announced,^[57][58] though the research was disputed,^[58][59] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.^[60]

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.^[62] 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.^[63] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.^[64]

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, known as a guanine tetrad, form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure.^[65] 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.^[66] 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.^[67] 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 or D-loop.^[65]

Branched DNA

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.^[68] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Artificial bases

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth.^[69][70] On the other hand, DNA is tightly related to RNA which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding RNA,^[71] while a higher number is also possible but this would be against the natural principle of least effort.

Acidity

The phosphate groups of DNA give it similar acidic properties to phosphoric acid and it can be considered as a strong acid. It will be fully ionized at a normal cellular pH, releasing protons which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by hydrolysis by repelling nucleophiles which could hydrolyze it.^[72]

Macroscopic appearance

Pure DNA extracted from cells forms white, stringy clumps.^[73]

Chemical modifications and altered DNA packaging

Base modifications and DNA packaging

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.^[74]

For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes.^[75] The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.^[76] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.^[77] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,^[78] and the glycosylation of uracil to produce the «J-base» in kinetoplastids.^[79][80]

Damage

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens 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 can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.^[82] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.^[83] A typical human cell contains about 150,000 bases that have suffered oxidative damage.^[84] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.^[85] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.^[86][87] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.^[88][89][90]

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.^[91] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.^[92] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.^[93] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.^[94]

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.^[95] 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. In an alternative fashion, a cell may copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.^[96] 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, and regulatory sequences such as promoters and enhancers, which control 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.^[97] The reasons for the presence of so much noncoding 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».^[98] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.^[99]

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes.^[63][101] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.^[102] 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.^[103]

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 TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA).

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. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix.^[104] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L.^[105] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;^[106] it may provide nutrients;^[107] and it may act as a buffer to recruit or titrate ions or antibiotics.^[108] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;^[109] it may contribute to biofilm formation;^[110] and it may contribute to the biofilm’s physical strength and resistance to biological stress.^[111]

Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.^[112]

Under the name of environmental DNA eDNA has seen increased use in the natural sciences as a survey tool for ecology, monitoring the movements and presence of species in water, air, or on land, and assessing an area’s biodiversity.^[113][114]

Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA, which allow neutrophils, a type of white blood cell, to kill extracellular pathogens while minimizing damage to the host cells.

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single 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.

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.^[115][116] 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 thus largely independent of the base sequence.^[117] Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation.^[118] 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.^[119] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.^[120] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.^[121]

A distinct group of DNA-binding proteins is 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.^[122] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

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.^[124] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.^[125]

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.^[126] 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.^[24]

DNA-modifying enzymes

Nucleases and ligases

Nucleases are enzymes that 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 endonucleases cut within strands. 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′-GATATC-3′ and makes a cut at the horizontal 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.^[128] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands.^[129] Ligases are particularly important in lagging strand DNA replication, as they join the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.^[129]

Topoisomerases and helicases

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.^[43] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.^[130] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.^[44]

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.^[131] These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction.^[132] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed.^[133] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.^[134]

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.^[62][135] For example, HIV reverse transcriptase is an enzyme for AIDS virus replication.^[135] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.^[63]

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.^[136]

Genetic recombination

A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called «chromosome territories».^[138] 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 in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.^[139] Genetic recombination can also be involved in DNA repair, particularly in the cell’s response to double-strand breaks.^[140]

The most common form of chromosomal crossover is 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 RAD51.^[141] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.^[142] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that 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.^[143] Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

Evolution

DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.^[144][145] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.^[146] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.^[147] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.^[148] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,^[149] but these claims are controversial.^[150][151]

Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space.^{[152][153][154]} Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.^[155]

In February 2021, scientists reported, for the first time, the sequencing of DNA from animal remains, a mammoth in this instance over a million years old, the oldest DNA sequenced to date.^[156][157]

Uses in technology

Genetic engineering

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to 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.^[158] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,^[159] or be grown in agriculture.^[160][161]

DNA profiling

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.^[162] This process is formally termed DNA profiling, also called DNA fingerprinting. 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.^[163] However, identification can be complicated if the scene is contaminated with DNA from several people.^[164] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,^[165] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.^[166]

The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.

DNA profiling is also used successfully to positively identify victims of mass casualty incidents,^[167] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.^[168]

DNA enzymes or catalytic DNA

Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994.^[169] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.^[170] The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),^[169] the CA1-3 DNAzymes (copper-specific),^[171] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).^[172] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

Bioinformatics

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory.^[173] 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.^[174] The DNA sequence may be aligned with other DNA sequences 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.^[175] Data sets representing entire genomes’ worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify 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 and their possible functions in an organism even before they have been isolated experimentally.^[176] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.^[178] 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 and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.^[179] Nanomechanical devices and algorithmic self-assembly have also been demonstrated,^[180] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.^[181] DNA and other nucleic acids are the basis of aptamers, synthetic oligonucleotide ligands for specific target molecules used in a range of biotechnology and biomedical applications.^[182]

History and anthropology

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.^[183] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology.

Information storage

DNA as a storage device for information has enormous potential since it has much higher storage density compared to electronic devices. However, high costs, slow read and write times (memory latency), and insufficient reliability has prevented its practical use.^[184][185]

History

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».^[186][187] In 1878, Albrecht Kossel isolated the non-protein component of «nuclein», nucleic acid, and later isolated its five primary nucleobases.^[188][189]

In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of RNA (then named «yeast nucleic acid»).^{[190][191][192]} In 1929, Levene identified deoxyribose sugar in «thymus nucleic acid» (DNA).^[193] Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups («tetranucleotide hypothesis»). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a «giant hereditary molecule» made up of «two mirror strands that would replicate in a semi-conservative fashion using each strand as a template».^[194][195] In 1928, Frederick Griffith in his experiment discovered that traits of the «smooth» form of Pneumococcus could be transferred to the «rough» form of the same bacteria by mixing killed «smooth» bacteria with the live «rough» form.^[196][197] This system provided the first clear suggestion that DNA carries genetic information.

In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in the cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, «yeast nucleic acid» (RNA) was thought to occur only in plants, while «thymus nucleic acid» (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.^[198][199]

In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.^[200]

In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith’s suggestion (Avery–MacLeod–McCarty experiment).^[201] Erwin Chargaff developed and published observations now known as Chargaff’s rules, stating that in DNA from any species of any organism, the amount of guanine should be equal to cytosine and the amount of adenine should be equal to thymine.^[202][203] Late in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. 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 enterobacteria phage T2.^[204]

In May 1952, Raymond Gosling, a graduate student working under the supervision of Rosalind Franklin, took an X-ray diffraction image, labeled as «Photo 51»,^[205] at high hydration levels of DNA. This photo was given to Watson and Crick by Maurice Wilkins and was critical to their obtaining the correct structure of DNA. Franklin told Crick and Watson that the backbones had to be on the outside. Before then, Linus Pauling, and Watson and Crick, had erroneous models with the chains inside and the bases pointing outwards. Franklin’s identification of the space group for DNA crystals revealed to Crick that the two DNA strands were antiparallel.^[206] In February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside.^[207] Watson and Crick completed their model, which is now accepted as the first correct model of the double helix of DNA. On 28 February 1953 Crick interrupted patrons’ lunchtime at The Eagle pub in Cambridge to announce that he and Watson had «discovered the secret of life».^[208]

The 25 April 1953 issue of the journal Nature published a series of five articles giving the Watson and Crick double-helix structure DNA and evidence supporting it.^[209] The structure was reported in a letter titled «MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid«, in which they said, «It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.»^[9] This letter was followed by a letter from Franklin and Gosling, which was the first publication of their own X-ray diffraction data and of their original analysis method.^[47][210] Then followed a letter by Wilkins and two of his colleagues, which contained an analysis of in vivo B-DNA X-ray patterns, and which supported the presence in vivo of the Watson and Crick structure.^[48]

In 1962, after Franklin’s death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.^[211] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.^[212]

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».^[213] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment.^[214] Further work by Crick and co-workers 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.^[215] These findings represent the birth of molecular biology.^[216]

See also

References

Further reading

External links

• DNA at Curlie
• DNA binding site prediction on protein
• DNA the Double Helix Game From the official Nobel Prize web site
• DNA under electron microscope
• Dolan DNA Learning Center
• Double Helix: 50 years of DNA, Nature
• Proteopedia DNA
• Proteopedia Forms_of_DNA
• ENCODE threads explorer ENCODE home page at Nature
• Double Helix 1953–2003 National Centre for Biotechnology Education
• Genetic Education Modules for Teachers – DNA from the Beginning Study Guide
• PDB Molecule of the Month DNA
• «Clue to chemistry of heredity found». The New York Times, June 1953. First American newspaper coverage of the discovery of the DNA structure
• DNA from the Beginning Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project.
• The Register of Francis Crick Personal Papers 1938 – 2007 at Mandeville Special Collections Library, University of California, San Diego
• Seven-page, handwritten letter that Crick sent to his 12-year-old son Michael in 1953 describing the structure of DNA. See Crick’s medal goes under the hammer, Nature, 5 April 2013.

Last Update: Jan 03, 2023

This is a question our experts keep getting from time to time. Now, we have got the complete detailed explanation and answer for everyone, who is interested!

Asked by: Ms. Kasey Daniel

Score: 4.6/5
(55 votes)

Deoxyribonucleic acid is a molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids.

What do the letters in DNA stand for?

What is DNA in full words?

= DNA is the chemical name for the molecule that carries genetic instructions in all living things. The DNA molecule consists of two strands that wind around one another to form a shape known as a double helix.

What does DNA stand for easy definition?

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA.

What does DNA stand for and pronounce it?

English pronunciation of deoxyribonucleic acid.

31 related questions found

DNA stands for deoxyribonucleic acid, and it’s a molecule that supplies the genetic instructions that tell living creatures how to develop, live and reproduce. DNA can be found inside every cell and is passed down from parents to their offspring. 

What is DNA made of?

DNA is made up of molecules called nucleotides. Each nucleotide contains three components: a phosphate group, which is one phosphorus atom bonded to four oxygen atoms; a sugar molecule; and a nitrogen base. The four types of nitrogen bases are adenine (A), thymine (T), guanine (G) and cytosine (C), and together, these serve as the «letters» that make up the genetic code of our DNA. 

DNA has a structure called a double helix. Nucleotides are attached together to form two long strands that spiral to create this structure. If you think of the double-helix  as a ladder, the phosphate and sugar molecules would be the sides, while the base pairs would be the rungs. The bases on one strand pair with the bases on another strand: Adenine pairs with thymine (A-T), and guanine pairs with cytosine (G-C).

Human DNA is made up of around 3 billion base pairs, and more than 99% of those bases are the same in all people, according to the U.S. National Library of Medicine (opens in new tab) (NLM).

Related: How accurate are DNA tests?

Similar to the way that letters in the alphabet can be arranged to form words, the order of nitrogen bases in a DNA sequence forms genes, which, in the language of the cell, tell cells how to make proteins. The shorthand for this process is that genes «encode» proteins. 

But DNA is not the direct template for protein production. To make a protein, the cell makes a copy of the gene, using not DNA but ribonucleic acid, or RNA. RNA shares a similar structure to DNA, except it contains only one strand, rather than two — so it looks like just one half of a ladder. In addition, while RNA has three of the four nitrogen bases in common with DNA, it uses a base called uracil rather than thymine to pair with adenine. 

As a cell prepares to build a new protein, its DNA unzips to expose one strand of the gene with the instructions to build said protein. Then, an enzyme zooms in and constructs a new RNA molecule whose sequence mirrors that of the unzipped gene. This RNA copy, called messenger RNA (mRNA), tells the cell’s protein-making machinery which amino acids to string together into a protein, according to «Biochemistry (opens in new tab)» (W. H. Freeman and Company, 2002).

DNA molecules are long — so long, in fact, that they can’t fit into cells without the right packaging. To fit inside cells, DNA is coiled tightly to form structures called chromosomes. Each chromosome contains a single DNA molecule, wrapped tightly around spool-like proteins called histones, which provide chromosomes their structure. Humans have 23 pairs of chromosomes, which are found inside each cell’s nucleus, the control center of the cell. 

Most chromosomes look like microscopic Xs; that said, humans and most other mammals carry a pair of sex chromosomes that can be either X or Y-shaped, according to the National Human Genome Research Institute (opens in new tab). In general, females carry two X sex chromosomes in each body cell and males carry one X and one Y. But there is some natural variation in the number of sex chromosomes people carry — sometimes, there may be extra sex chromosomes, or one might be missing, so other patterns, such as X, XXX, XXY and XXYY, can also occur, Discover reported (opens in new tab). 

Who discovered DNA?

(opens in new tab)

DNA was first observed by Swiss biochemist Friedrich Miescher in 1869, according to a paper published in 2005 in the journal Developmental Biology (opens in new tab). Miescher used biochemical methods to isolate DNA — which he then called nuclein — from white blood cells and sperm, and determined that it was very different from protein. (The term «nucleic acid» derives from «nuclein.») 

But for many years, researchers did not realize the importance of this molecule. 

In 1952, chemist Rosalind Franklin, who was working in the lab of biophysicist Maurice Wilkins, used X-ray diffraction — a way of determining the structure of a molecule by the way X-rays bounce off it — to learn that DNA had a helical structure. Franklin documented this structure in what became known as Photo 51. 

In 1953, Wilkins showed the photo to biologists James Watson and Francis Crick — without Franklin’s knowledge. Armed with the information that DNA was a double helix and previous reports that the bases adenine and thymine occurred in equal amounts within DNA, as did guanine and cytosine, Watson and Crick published a landmark 1953 paper in the journal Nature (opens in new tab). In that paper, they proposed the iconic double-helix model of DNA as we now know it, with sugar-phosphate sides and rungs made up of A-T and G-C base pairs. They also suggested that, based on their proposed structure, DNA could be copied — and, therefore, passed on. 

Watson, Crick and Wilkins were awarded the Nobel Prize in medicine in 1962 «for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.» Franklin was not included in the award, even though her work was integral to the research. 

What is the function of DNA?

Genes encode proteins that perform all sorts of functions for humans (and other living beings). 

The human gene HBA1, for example, contains instructions for building the protein alpha globin, which is a component of hemoglobin, the oxygen-carrying protein in red blood cells, according to the NLM (opens in new tab). To take another example, the gene OR6A2 encodes an olfactory receptor, a protein that detects odors in the nose, according to the National Center for Biotechnology Information’s Gene database (opens in new tab). Depending on which version of OR6A2 you have, you may love cilantro or think it tastes like soap, according to a study published in 2012 in the journal Flavour (opens in new tab).

Although each one of your 37.2 trillion cells carries a copy of your DNA, not all cells build the same proteins. One reason for this is that molecules called «transcription factors» latch onto DNA to control which genes get switched on and off, and therefore, which proteins get made when, where and in what quantities in each cell, Live Science previously reported. DNA also gets packaged slightly differently in different cell types, and this influences how and where transcription factors can grab onto the molecule. 

In addition, epigenetics — which literally means «above» or «on top of» genetics — refers to external modifications to DNA that turn specific genes on or off. 

For instance, small molecules called methyl groups can attach to a DNA strand and prevent specific genes from being expressed. Another example of epigenetics is called «histone modification,» where changes to the spool-like proteins inside chromosomes can make specific segments of DNA more or less accessible to the proteins that «read» genes. Such epigenetic changes to DNA can be passed onto future generations if the changes occur in sperm or egg cells, Live Science previously reported. 

How is DNA sequenced?

DNA sequencing involves technology that allows researchers to determine the order of bases in a section of DNA. The technology can be used to determine the order of bases in genes, chromosomes or an entire genome. In 2000, researchers completed a «working draft» sequence of the human genome, according to the National Human Genome Research Institute (opens in new tab), and finished the project in 2003.

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DNA testing

A person’s DNA contains information about their heritage, and it can sometimes reveal whether they are at an elevated risk for certain diseases. 

DNA tests, or genetic tests, are used for a variety of reasons, including to diagnose genetic disorders, to determine whether a person is a carrier of a genetic mutation that they could pass on to their children and to examine whether a person is at risk for a genetic disease. For instance, certain mutations in the BRCA1 and BRCA2 genes are known to increase the risk of breast and ovarian cancers, and a genetic test can reveal whether a person has these mutations.

Genetic test results can have implications for a person’s health, and the tests are often provided along with genetic counseling to help individuals understand the results and consequences.

People also use the results of genetic testing to find relatives and learn about their family trees through companies such as Ancestry and MyHeritage.

Additional resources and reading

•  Learn about how much of your DNA is just «junk» with SciShow on Youtube (opens in new tab). 
•  Read more about how DNA testing works with Science News for Students (opens in new tab). 
•  Check out renowned science writer Carl Zimmer’s 2018 book, «She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity (opens in new tab).» 

Bibliography

Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). DNA, RNA, and the Flow of Genetic Information. In Biochemistry (5th ed.). chapter, W H Freeman & Co. 

Dahm, R. (2005). Friedrich Miescher and the discovery of DNA. Developmental Biology, 278(2), 274–288. https://doi.org/10.1016/j.ydbio.2004.11.028 (opens in new tab) 

Eriksson, N., Wu, S., Do, C. B., Kiefer, A. K., Tung, J. Y., Mountain, J. L., Hinds, D. A., & Francke, U. (2012). A genetic variant near olfactory receptor genes influences cilantro preference. Flavour, 1(1). https://doi.org/10.1186/2044-7248-1-22 (opens in new tab) 

Incorvaia, D. (2021, September 28). Sex is more complex than a simple binary suggests. Discover Magazine. Retrieved January 14, 2022, from https://www.discovermagazine.com/the-sciences/sex-is-more-complex-than-a-simple-binary-suggests (opens in new tab) 

NIH National Human Genome Research Institute. (2021, February 12). Human genome project timeline of events. Genome.gov. Retrieved January 14, 2022, from https://www.genome.gov/human-genome-project/Timeline-of-Events (opens in new tab) 

NIH National Human Genome Research Institute. (n.d.). Sex chromosome. Genome.gov. Retrieved January 14, 2022, from https://www.genome.gov/genetics-glossary/Sex-Chromosome (opens in new tab) 

U.S. National Library of Medicine. (2020, September 28). HBA1 gene. MedlinePlus. Retrieved January 14, 2022, from https://medlineplus.gov/genetics/gene/hba1/ (opens in new tab) 

U.S. National Library of Medicine. (2022, January 5). OR6A2 olfactory receptor family 6 subfamily a member 2 [homo sapiens (human)] — gene — NCBI. National Center for Biotechnology Information. Retrieved January 14, 2022, from https://www.ncbi.nlm.nih.gov/gene/8590 (opens in new tab) 

U.S. National Library of Medicine. (2021, January 19). What is DNA?: Medlineplus Genetics. MedlinePlus. Retrieved January 14, 2022, from https://medlineplus.gov/genetics/understanding/basics/dna/ (opens in new tab) 

Watson, J. D., & Crick, F. H. (1953). Molecular structure of Nucleic Acids: A structure for deoxyribose nucleic acid. Nature, 171(4356), 737–738. https://doi.org/10.1038/171737a0 (opens in new tab) 

Additional reporting by Alina Bradford and Ashley P. Taylor, Live Science contributors, as well as Live Science staff writer Nicoletta Lanese. This page was last updated on Jan. 26, 2022.

Originally published on Live Science.

Rachael is a Live Science contributor, and was a former channel editor and senior writer for Live Science between 2010 and 2022. She has a master’s degree in journalism from New York University’s Science, Health and Environmental Reporting Program. She also holds a B.S. in molecular biology and an M.S. in biology from the University of California, San Diego. Her work has appeared in Scienceline, The Washington Post and Scientific American.

Deoxyribonucleic acid—or DNA— is a molecule that serves as the hereditary material containing biological instructions that make every human and other organism unique. During reproduction, adult organisms pass their DNA and its set of instructions along to their offspring.

The Structure and Makeup of DNA

DNA is made up of nucleotides, which are essentially chemical building blocks. Nucleotides join together in chains to form a strand of DNA, and contain three parts: a phosphate group, a sugar group, and one of four types of chemical bases:

• Adenine (A)
• Guanine (G)
• Cytosine (C)
• Thymine (T)

These chemical bases come together to create the information found in DNA, and stores it in a code, based on their sequence. A human genome—or the full set of instructions from DNA—contains about 3 billion bases and about 20,000 genes on 23 pairs of chromosomes.

Where DNA Is Found

DNA is found in nearly every cell of the human body. It is primarily located in the nucleus (where it is also referred to as «nuclear DNA»), though there is also a small amount in the mitochondria as well. Mitochondria are another part of human cells and are in charge of converting energy from food into a form that can power the cells. Collectively, all the nuclear DNA in an organism is known as its «genome.»

How DNA Works

The purpose of DNA is to instruct organisms—including humans—on how to develop, survive, and reproduce. In order for this to happen, DNA sequences—known as «genes»—are converted into proteins, which are complex molecules responsible for carrying out most of the work in human bodies. While genes vary in size—ranging from about 1,000 bases to 1 million bases in humans—they only make up approximately 1% of the DNA sequence. The rest of the DNA sequences regulate when, how, and how much of a protein is made.

It takes two separate steps to make proteins using instructions from DNA. The first is when enzymes read the information delivered in a DNA molecule and then transcribe it to a separate molecule called messenger ribonucleic acid, or mRNA. Once that happens, the information sent by the mRNA molecule is then translated into a language that amino acids—also known as the building blocks of proteins—can understand. The cell applies those instructions in order to link the correct amino acids together to create a specific type of protein. Given that there are 20 types of amino acids that can be put together in many possible orders and combinations, it gives DNA the opportunity to form a wide range of proteins.

The Double Helix

To understand how DNA works, it’s important to go back to the four chemical bases mentioned earlier: A, G, C, and T. They each pair up with another base in order to create units called «base pairs.» Then, each base also attaches to a sugar molecule and a phosphate molecule, forming a nucleotide. When arranged in two long strands, nucleotides form what looks like a twisted ladder or spiral staircase known as a «double helix.» Using the example of a ladder, the base pairs are the rungs, while the sugar and phosphate molecules form the vertical sides of the ladder, holding it all together.

The shape of the double helix is what gives DNA the capability to pass along biological instructions with great accuracy. This is the case because the spiral shape is the reason DNA is able to replicate itself during cell division. When it comes time for a cell to divide, the double helix separates down the middle to become two single strands. From there, the single strands function as templates to form new double helix DNA molecules, which—once the bases are partnered and added to the structure—turns out as a replica of the original DNA molecule.

The History and Discovery of DNA

In 1869, Swiss physician and biochemist Friedrich Miescher discovered a chemical substance in human leucocytes. His research focused on the chemical contents of a cell’s nucleus, and in order to get a better look at them, he examined pus on surgical bandages from the local hospital. Pus was known to contain large amounts of leucocytes, so Miescher purified their nuclei to better understand their makeup. In doing so, he was able to isolate a new chemical substance in the nucleus, which he named «nuclein»—but is known today as DNA. While there was a significant amount of research done on nucleic acids during and shortly after Miescher’s lifetime, it would take several more decades before scientists understood their significance.

There was a renewed interest in DNA starting in the 1930s, with many major discoveries soon following, including the understanding that DNA was responsible for passing along hereditary characteristics. The structure of DNA was also the subject of research in the 1930s, including that of English physicist and molecular biologist William T. Astbury, who suggested that DNA was a long and helical linear molecule.

The best-known DNA breakthrough came in 1953, when Rosalind Franklin, James Watson, Francis Crick, and Maurice Wilkins conducted research that would result in the discovery of the double helix model of DNA. Using X-ray diffraction patterns and building models, the scientists determined that the double helix structure of DNA enabled it to carry biological information from one generation to the next.

In 1962, Watson, Crick, and Wilkins were awarded the Nobel Prize in medicine for their discovery. Though Franklin would have been eligible to receive the prize, she died in 1958 from ovarian cancer at the age of 37, and the Nobel Prize rules stipulate that the award can’t be split among more than three people, or given out after someone has died.

A Word From Verywell

Like many scientists who researched genetics in the field’s early days, Watson was known to hold damaging—and scientifically inaccurate—beliefs on race, ethnicity, gender, and sexual identity, among other demographics. While the discoveries he made alongside his colleagues were significant, it’s also important to acknowledge aspects of his work that don’t hold up today.

DNA Definition

Deoxyribonucleic acid, or DNA, is a biological macromolecule that carries hereditary information in many organisms. DNA is necessary for the production of proteins, the regulation, metabolism, and reproduction of the cell. Large compressed DNA molecules with associated proteins, called chromatin, are mostly present inside the nucleus. Some cytoplasmic organelles like the mitochondria also contain DNA molecules.

DNA is usually a double-stranded polymer of nucleotides, although single-stranded DNA is also known. Nucleotides in DNA are molecules made of deoxyribose sugar, a phosphate and a nitrogenous base. The nitrogenous bases in DNA are of four types – adenine, guanine, thymine and cytosine. The phosphate and the deoxyribose sugars form a backbone-like structure, with the nitrogenous bases extending out like rungs of a ladder. Each sugar molecule is linked through its third and fifth carbon atoms to one phosphate molecule each.

Functions of DNA

DNA was isolated and discovered chemically before its functions became clear. DNA and its related molecule, ribonucleic acid (RNA), were initially identified simply as acidic molecules that were present in the nucleus. When Mendel’s experiments on genetics were rediscovered, it became clear that heredity was probably transmitted through discrete particles, and that there was a biochemical basis for inheritance. A series of experiments demonstrated that among the four types of macromolecules within the cell (carbohydrates, lipids, proteins and nucleic acids), the only chemicals that were consistently transmitted from one generation to the next were nucleic acids.

As it became clear that DNA was the material that was transferred from one generation to the next, its functions began to be investigated.

Replication and Heredity

Every DNA molecule is distinguished by its sequence of nucleotides. That is, the order in which nitrogenous bases appear within the macromolecule identify a DNA molecule. For instance, when the human genome was sequenced, the nucleotides constituting each of the 23 pairs of chromosomes were laid out, like a string of words on a page. There are individual differences in these nucleotide sequences, but overall, for every organism, large stretches are conserved. The sugar phosphate backbone, on the other hand, is common to all DNA molecules, across species, whether in bacteria, plants, invertebrates or humans.

When a double-stranded DNA molecule needs to be replicated, the first thing that happens is that the two strands separate along a short stretch, creating a bubble-like structure. In this transient single-stranded region, a number of enzymes and other proteins, including DNA polymerase work to create the complementary strand, with the correct nucleotide being chosen through hydrogen bond formation. These enzymes continue along each strand creating a new polynucleotide molecule until the entire DNA is replicated.

Life begins from a single cell. For humans, this is the zygote formed by the fertilization of an egg by a sperm. After this, the entire dazzling array of cells and tissue types are produced by cell division. Even the maintenance of normal functions in an adult requires constant mitosis. Each time a cell divides, nuclear genetic material is duplicated. This implies that nearly 3 billion nucleotides are accurately read and copied. High-fidelity DNA polymerases and a host of error repair mechanisms ensure that there is only one incorrectly incorporated nucleotide for every 10 billion base pairs.

Transcription

The second important function of genetic material is to direct the physiological activities of the cell. Most catalytic and functional roles in the body are carried out by peptides, proteins and RNA. The structure and function of these molecules is determined by nucleotide sequences in DNA.

When a protein or RNA molecule needs to be produced, the first step is transcription. Like DNA replication, this begins with the transient formation of a single-stranded region. The single-stranded region then acts as the template for the polymerization of a complementary polynucleotide RNA molecule. Only one of the two strands of DNA is involved in transcription. This is called the template strand and the other strand is called the coding strand. Since transcription is also dependent on complementary base pairing, the RNA sequence is nearly the same as the coding strand.

In the image, the coding strands and the template strands are depicted in orange and purple respectively. RNA is transcribed in the 5’ to 3’ direction.

Mutation and Evolution

One of the main functions of any hereditary material is to be replicated and inherited. In order to create a new generation, genetic information needs to be accurately duplicated and then transmitted. The structure of DNA ensures that the information coded within every polynucleotide strand is replicated with astonishing accuracy.

Even though it is important for DNA to be duplicated with a very high degree of accuracy, the overall process of evolution requires the presence of genetic variability within every species. One of the ways in which this happens is through mutations in DNA molecules.

Changes to the nucleotide sequence in genetic material allows for the formation of new allele. Alleles are different, mostly functional, varieties of every gene. For instance, people who have B blood group have a certain gene resulting in a particular surface protein on red blood cells. This protein is distinct from the surface antigens in those who have blood group A. Similarly, people with sickle cell anemia have a different hemoglobin allele compared to those who do not suffer from the illness.

The presence of this variability allows at least some populations to survive when there is a sudden and drastic change to the environment. For instance, individuals carrying a mutated allele for hemoglobin are at risk for sickle cell anemia. However, they also have a higher chance of survival in regions where malaria is endemic.

These mutations and the presence of variability allow populations to evolve and adapt to changing circumstances.

Genetic Engineering

On another level, DNA’s role as genetic material and an understanding of its chemistry allows us to manipulate it and use it to enhance quality of life. For example, genetically modified crops that are pest or drought resistant have been generated from wild type varieties through genetic engineering. A lot of molecular biology is dependent on the isolation and manipulation of DNA, for the study of living processes.

Structure of DNA

When its definitive role in heredity was established, understanding DNA’s structure became important. Previous work on protein crystals guided the interpretation of crystallization and X-Ray differaction of DNA. The correct interpretation of diffraction data started a new era in understanding and manipulating genetic material. While initially, scientists like Linus Pauling suggested that DNA was perhaps made of three strands, Rosalind Franklin’s data supported the presence of a double helix.

The structure of DNA therefore, was elucidated in a step-wise manner through a series of experiments, starting from the chemical isolation of deoxyribonucleic acid by Frederich Miescher to the X-ray crystallography of this macromolecule by Rosalind Franklin.

Double Helix and Antiparallel Strands

The image is a simplified representation of a short DNA molecule, with deoxyribose sugar molecules in orange, linked to phosphate molecules through a special type of covalent linkage called the phosphodiester bond. Each nitrogenous base is represented by a different color – thymine in purple, adenine in green, cytosine in red and guanine in blue. The bases from each strand form hydrogen bonds with one another, stabilizing the double-stranded structure.

The structure of the sugar phosphate backbone in a DNA molecule results in a chemical polarity. Each deoxyribose sugar has five carbon atoms. Of these, the third and the fifth carbon atoms can form covalent bonds with phosphate moieties through phosphodiester bonds. A phosphodiester linkage essentially has a phosphate molecule forming two covalent bonds and a series of these bonds creates the two spines of a double-stranded DNA molecule.

Alternating sugar and phosphate residues results in one end of every DNA strand having a free phosphate group attached to the fifth carbon of a deoxyribose sugar. This is called the 5’ end. The other end has a reactive hydroxyl group attached to the third carbon atom of the sugar molecule and makes the 3’ end.

The two strands of every DNA molecule have opposing chemical polarities. That is, at the end of every double-stranded DNA molecule, one strand will have a reactive 3’ hydroxyl group and the other strand will have the reactive phosphate group attached to the fifth carbon of deoxyribose. This is why a DNA molecule is said to be made of antiparallel strands.

A DNA molecule can look like a ladder, with a sugar phosphate backbone and nucleotide rungs. However, a DNA molecule forms a three-dimensional helical structure, with the bases tucked inside the double helix. Hydrogen bonding between nucleotides allows the intermolecular distance between two strands to remain fairly constant, with ten base pairs in every turn of the double helix.

Complementarity and Replication

Nucleotide bases on one strand interact with those on the other strand through two or three hydrogen bonds. This pattern is predictable (though exceptions exist), with every thymine base pairing with an adenine base, and the guanine and cytosine nucleotides forming hydrogen bonds with each other. Due to this, when the sequence of a single strand is known, the nucleotides present in the complementary strand of DNA are automatically revealed. For instance, if one strand of a DNA molecule has the sequence 5’ CAGCAGCAG 3’, the bases on the other antiparallel strand that pair with this stretch will be 5’ CTGCTGCTG 3’. This property of DNA double strands is called complementarity.

Initially, there was debate about the manner in which DNA molecules are duplicated. There were three major hypotheses about the mechanism of DNA replication. The two complementary strands of DNA could unwind at short stretches and provide the template for the formation of a new DNA molecule, formed completely from free nucleotides. This method was named the conservative hypothesis.

Alternatively, each template strand could catalyze the formation of its complementary strand through nucleotide polymerization. In this semi-conservative mode of replication, all duplicated DNA molecules would carry one strand from the parent and one newly synthesized strand. In effect, all duplicated DNA molecules would be hybrids. The third hypothesis stated that every large DNA molecule was probably broken into small segments before it was replicated. This was called the dispersive hypothesis and would result in mosaic molecules.

A series of elegant experiments by Matthew Meselson, and Franklin Stahl, with help from Mason MacDonald and Amandeep Sehmbi, supported the idea that DNA replication was, in fact, semi-conservative. At the end of every duplication event, all DNA molecules carry one parental strand and one strand newly created from nucleotide polymerization.

Discovery of DNA

As microscopes started to become more sophisticated and provide greater magnification, the role of the nucleus in cell division became fairly clear. On the other hand, there was the common understanding of heredity as the ‘mixing’ of maternal and paternal characteristics, since the fusion of two nuclei during fertilization had been observed.

However, the discovery of DNA as the genetic material probably began with the work of Gregor Mendel. When his experiments were rediscovered, an important implication came to light. His results could only be explained through the inheritance of discrete particles, rather than through the diffuse mixing of traits. While Mendel called them factors, with the advent of chemistry into biological sciences, a hunt for the molecular basis of heredity began.

Chemical Isolation of DNA

DNA was first chemically isolated and purified by Johann Friedrich Miescher who was studying immunology. Specifically, he was trying to understand the biochemistry of white blood cells. After isolating the nuclei from the cytoplasm, he discovered that when acid was added to these extracts, stringy white clumps that looked like a tufts of wool, separated from the solution. Unlike proteins, these precipitates went back into solution upon the addition of an alkali. This led Miescher to conclude that the macromolecule was acidic in nature. When further experiments showed that the molecule was neither a lipid nor a protein, he realized that he had isolated a new class of molecules. Since it was derived from the nucleus, he named this substance nuclein.

The work of Albrecht Kossel shed more light on the chemical nature of this substance when he showed that nuclein (or nucleic acid as it was beginning to be called) was made of carbohydrates, phosphates, and nitrogenous bases. Kossel also made the important discovery connecting the biochemical study of nucleic acids with the microscopic analysis of dividing cells. He linked this acidic substance with chromosomes that could be observed visually and confirmed that this class of molecules was nearly completely present only in the nucleus. The other important discovery of Kossel’s was to link nucleic acids with an increase in protoplasm, and cell division, thereby strengthening its connection with heredity and reproduction.

Genes and DNA

By the turn of the twentieth century, molecular biology experienced a number of seminal discoveries that brought about an enhanced understanding of the chemical basis of life and cell division. In 1944, experiments by three scientists, (Avery, McCarty and McLeod) provided strong evidence that nucleic acids, specifically DNA, was probably the genetic material. A few years later, Chargaff’s experiments showed that the number of purine bases in every DNA molecule equaled the number of pyrimidine bases. In 1952, an elegant experiment by Alfred Hershey and Martha Chase confirmed DNA as the genetic material.

By this time, advances in X-Ray crystallography had allowed the crystallization of DNA and study of its diffraction patterns. Finally, these molecules could be visualized with greater granularity. The data generated by Rosalind Franklin allowed James Watson and Francis Crick to then propose the double-stranded helical model for DNA, with a sugar-phosphate backbone. They incorporated Chargaff’s rules for purine and pyrimidine quantities by showing that every purine base formed specific hydrogen bond linkages with another pyrimidine base. They understood even as they proposed this structure that they had provided a mechanism for DNA duplication.

In order to visualize this molecule, they built a three-dimensional model of a double helical DNA, using aluminum templates. The image above shows the template of the base Thymine, with accurate bond angles and lengths.

The final model built by Watson and Crick (as seen above) is now on display at the National Science Museum in London.

Quiz

1. Which of these statements about DNA is NOT true?
A. In eukaryotes, DNA is present exclusively in the nucleus
B. DNA is the genetic material for some viruses
C. DNA replication is semi-conservative
D. None of the above

2. Which of these scientists designed an experiment to show that DNA replication was semi-conservative?
A. Meselson
B. James Watson
C. Linus Pauling
D. All of the above

3. Why was the rediscovery of Mendel’s experiments important for the development of molecular biology?
A. Mendel’s experiments suggested that DNA was the hereditary material
B. Mendel’s laws of inheritance suggested that there were discrete biochemical particles involved in heredity
C. Mendel’s experiments with pea plants gave molecular biologists a useful model organism
D. All of the above

References

• Alberts, Bruce, et al. (2002). Molecular Biology of the Cell, 4th. ed. Ch. 4. Garland Science: New York. ISBN: 978-0815316206.
• Lodish H, et al., (2000) Molecular Cell Biology. 4th ed. W. H. Freeman: New York. ISBN-10: 0-7167-3136-3.
• Nobel Media AB (2014) “The Nobel Prize in Physiology or Medicine 1910” Nobelprize.org. Retrieved 10 May 2017 from http://www.nobelprize.org/nobel_prizes/medicine/laureates/1910/

What is DNA?

Simply put, DNA (Deoxyribonucleic Acid) is a string of nitrogenous bases (Adenine, Thymine, Guanine, and Cytosine) repeated over and over, and arranged in a seemingly random fashion. Here the genetic code is contained. These bases are connected to each other through chemical bonds. Two complementary strands of DNA are bonded to each other, and are twisted in a helical structure. This extremely long double-stranded twisted string has parts that code for everything in all organisms. Different parts are under different selection pressures.

Below we will outline the history, structure of DNA, the differences and similarities between DNA and RNA. After this, we will then dive into why DNA is so important. Given how important this structure is, we will also talk about how it is replicated (DNA replication), packaged, and how these can be exploited or used for DNA fingerprinting.

History of DNA

The discovery of the structure of DNA opened many avenues in the field of biology. In 1962, Watson, Crick, and Wilkins obtained a Nobel Peace Prize for describing it. However, its existence was known of before that.  In 1866, Gregor Mendel first hypothesized the existence of inherited entities, now known as genes. Later on (1869), Friedrich Miescher noted an acidic substance in the cell’s nuclei; this substance was referred to as nuclein (we now know this as DNA). Rosalind Franklin captured the famous X-Ray imagery clearly showing its double helical nature. It is her work together with that of the above-mentioned Nobel Laureates that gave us the gold mine (DNA) that has led to advances in all fields of biology; most notably, medicine.

This part of the DNA story is a lot more complex than this, but we will end here for the purpose of this lesson.

DNA Structure

DNA is a nucleic acid, hinted at in the name. Nucleic acids are the building blocks of all living organisms. Nucleotides simply refer to nitrogenous bases, pentose sugar together with the phosphate backbone. Nucleotides are adjacently strung together through a phosphate backbone and are held together with their complements through hydrogen bonds. The number of bonds holding nucleotides from the complementary strands depends on the type of nitrogenous base the nucleotide contains.

A nitrogenous base is a molecule with nitrogen that possesses the chemical properties of a base. These are crucial to the DNA as they define the genetic code (they are the code!). The pentose sugar connects the nitrogenous base to the phosphate backbone. There are four kinds of nitrogenous bases; namely, thymine (T), cytosine (C), adenine (A) and guanine (G). Guanine and adenine are purines while thymine and cytosine are pyrimidines. Purines have two rings (see adenine on figure 2) while pyrimidines have one ring. For the structure of the DNA to be able to twist and be packaged accordingly without bulging and the opposite bases to be able to pair up, a purine has to fit in a pyrimidine. To this end, the purine guanine pairs with the pyrimidine cytosine and the purine adenine pairs with the pyrimidine thymine.

Differences and Similarities between DNA and RNA

Both molecules are nucleic acids made up of nucleotides, supported by a phosphate backbone. They are both major players in the central dogma. RNA is transcribed from the DNA to make proteins. DNA carries all the information needed for DNA replication and transfer new information to new cells.

They are involved in the maintenance, replication, and expression of hereditary information. DNA holds the key to heredity. RNA helps DNA unlock this code and show us what this code is capable of achieving. Together these molecules ensure that the DNA is replicated, the code is translated, expressed and that things go where they should go.

DNA and RNA work hand in hand in biology. It is rare that one can speak of the one without bringing up the other. Simply put, they are connected by the central dogma. The central dogma is the process of DNA transcription and translation for the purpose of protein synthesis which then perform a multitude of tasks in organisms. Different types of proteins guide the gene expression. Therefore, even though the DNA is the same throughout- different things happen at different part of the body. In addition to this, it also tells stem cells what to differentiate to. This is due to strict regulatory mechanisms in place to control gene expression.

Both DNA and RNA have a negative backbone (because of the phosphate group). They both have four nucleotides each, three of which they share (Guanine, Cytosine, and Adenine); with one significant difference, DNA has Thymine while RNA has Uracil. DNA is double-stranded while RNA is single-stranded. Last but not least, DNA is found in the nucleus while RNA resides both in the nucleus and the cytoplasm. DNA is long-lived while RNA is regenerated with each reaction.

They are both central to cell function.

DNA Packaging

How does DNA fit into the cell? Consider this; each and every one of your cells contains approximately 6 billion base pairs of DNA, with each base pair being 0.34 nanometers long. This works out to about 2 meters of DNA per diploid cell! If the DNA sequence is so long how does the nucleus manage to house the DNA and many other components necessary for the functioning of the cell? The answer is very simple, through condensing and packaging.

DNA is packaged with the help of histone proteins. Histones are small proteins with basic, positively charged amino acids; namely, arginine and lysine. They bind and neutralize the negatively charged DNA (because of the negatively charged phosphate backbone). It takes five types of histones to package DNA; H1, H2A, H2B, H3, and H4. Core histones (H2A, H2B, H3, and H4) with DNA coiled around them are referred to as nucleosomes. It takes two of each of the core histones to make up a nucleosome. Per nucleosome an H1 histone sits outside the coil holding the nucleosome intact. The nucleosome together with histone H1 are collectively referred to as chromatosome. The nucleosomes are condensed to fibers called chromatin. Bigger loops of tightly packed chromatin then make chromosomes.

Keeping DNA in a coiled and inaccessible state ensures DNA safety. As you can imagine, with this much coiling, twisting and packing the DNA is not accessible for transcription and/ or replication. This becomes redundant if the DNA cannot perform its functions. For DNA to perform its functions it needs to be unpacked and made accessible again. It is in this state that DNA can be replicated in order to, amongst other things; accommodate organism’s growth and maturity through cell division facilitated by DNA replication to ensure there is sufficient DNA in every cell.

DNA Replication

To understand DNA replication you will need to keep the following in mind:

– Replication duplicates the genetic information; this means you end up with a collection of identical DNA strands.

– The rules of DNA replication (A to T; G to C) govern replication.

– Each of the two strands DNA serves as a template of the new strand.

-DNA replication is essential for cell division.

DNA replication takes place in 5’®3’ direction. This means that bases will be added from left to right direction. The template strand will guide this process by telling the new strand which base comes next, this will go on until the new strand is complete and the DNA will once again be double-stranded. Both strands of the old DNA will serve as templates of two new strands. This means that at the end there will be two double-stranded DNAs, identical to each other. This way once cell division occurs, the new cells will contain identical information as the rest of the body. A slew of proteins oversee the whole process make sure things happen at the right time and in the right way.

Due to the complementary nature of DNA, one strand is in the 5’®3’ direction while the other is in the 3’®5’ direction. The fore is referred to as the lagging strand while the latter is called the leading strand.

In preparation for DNA replication, the double-strand unwinds and separate to form replication forks. Each template strand attracts the complements to the now exposed bases; this happens in a stepwise fashion. The back-bone solidifies and the DNA rewinds. This is a very simplified version of the process. What follows is the detailed version with the enzymes involved to guide the process.

An enzyme called helicase unwinds the template strands. The single strand binding proteins then stabilize the template strands in preparation for the replication, it holds it open until the end of the replication process. DNA polymerase III synthesizes nucleotides onto the leading end in the 5’®3′ direction.

The replication directed by the lagging strand, however, is a little more complicated. Helicase can only synthesize in the 5’®3′ direction, this poses a problem where the only available direction is 3’®5’. To get around this, Okazaki fragments are synthesized. Primase, as the name suggests, primes the synthesis of the new strand through synthesizing RNA primers to direct the addition of Okazaki fragments. Okazaki fragments are added onto the lagging strand by DNA ligase bonding the 3’ end to the 5’ of the previous fragment. The primers that prime the addition of the Okazaki fragments are then removed by DNA polymerase I and replaced by DNA bases. At the end of the process after the removal of the last primer there is an exposed 3’ end. DNA polymerase III completes the synthesis of the new strand, by adding DNA nucleotides at the end of the new strand. Nuclease provides proofreading services, correcting mistakes made during replication. As you can imagine, there will be a very tight coil at the end of the replication fork. Topoisomerase fixes this problem by making a small nick that releases the tension build up.

DNA Comparison and DNA Fingerprinting

DNA information has been used in comparative studies in order to understand not just where we stand as a species in the animal kingdom but where other species fit and how their genetic make-up influences their way of living. DNA fingerprinting, also called DNA profiling, refers to a technique of using a collection of individual specific regions of their genome. This is based on the idea that different combinations of various regions of the genome are very unlikely to be shared across individual. So, for example even though some of these sections can be shared between family members it is highly unlikely that they would all be identical between family members.

Different parts of the DNA code are under stricter selection pressures. This fact is one of the most exploited properties of the genome when studying organisms at different levels (e.g. population level, species level, genus level, etc.). Gene regions such as those coding for the internal transcriber region of the ribosome are under somewhat strict controls, and these evolve relatively slow. These, can, therefore, be used to study variations at the species level (species level marker). Other markers are under very little to no selection (neutral selection) and therefore evolve more freely, for example, simple sequence repeats such as micro satellites. These are more informative and can be used to study population dynamics. Some areas evolve so fast that they can be used to identify and different between individuals in a population to differentiating between individuals born of the same parents.

Using regions in the nuclear DNA to identify individuals, species or higher taxa is what we refer to as DNA bar coding. To study population dynamics markers such micro-satellites prove useful as their polymorphic profile can tell us a lot about how often intra and inter-breeding occur within and across populations. It can also give clues to infer modes of dispersal. To study evolutionary processes and phylogenetic relationships slow evolving markers such as mitochondrial DNA can be used. These can tell us where species sit in the bigger picture.

There are a large variety of fields in biology that exist because of the ability to study and manipulate the DNA code. These include fields such as genetic engineering; this is how you can enjoy summer fruits in winter. Other fields include gene therapy; here biologists use the knowledge of the genome to manipulate specific parts of the genome to remove lethal variants of some genes. The availability of techniques such as DNA fingerprinting also helps to better understand genetic diseases, and with the help of research such as that into CRISPR-CAS9, hopefully, enable us to cure diseases such as cancer.

Is DNA Important?

The simple answer is, yes, very much so. We hope at this point you agree with this answer. Just think of all the things DNA code for (pretty much everything). Now imagine life without them. What is left? Is any of it biotic?

DNA is what makes you special, alive and functional. Without DNA you would not exist. Everything you have, the thing you consider your best feature would not exist without DNA. DNA directs cell function. If there was no DNA, cell division would not happen—therefore no differentiation, this means you would not exist neither would your pet. Even though DNA is not solely responsible for life as we know it is still arguably the most important factor. Other factors include the environment and experience.
DNA is important for many reasons—so many in fact that we cannot list them all. To name a few it is important in the fields of genealogy, forensic science, agriculture, and virology.

Conclusion

In conclusion, DNA forms the basis for life. The discovery of the DNA structure has led to major strides in research, medicine, agriculture and many other fields. Given how important this structure is to our existence, it only makes sense that its description has affected so many areas of our lives. We hope at this point you have as much appreciation as we do for what DNA is and can do, how is differs from RNA, how many lives it has revolutionized and DNA fingerprinting. At this point, you should also have an appreciation for what DNA is in biology and what it means for this field.

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This page was last updated on 2022-02-18