Deoxyribonucleic acid (/diˌɒksiˌraɪbɵ.njuːˌkleɪ.ɨk ˈæsɪd/ ( listen)), or DNA, is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints, like a recipe or a code, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.
DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called bases. It is the sequence of these four bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA, in a process called transcription.
Within cells, DNA is organized into long structures called chromosomes. These chromosomes are duplicated before cells divide, in a process called DNA replication. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.
DNA is a long polymer made from repeating units called nucleotides. As first discovered by James D. Watson and Francis Crick, the structure of DNA of all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34 Ångströms (3.4 nanometres) and a radius of 10 Ångströms (1.0 nanometres). According to another study, when measured in a particular solution, the DNA chain measured 22 to 26 Ångströms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long. Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the largest human chromosome, chromosome number 1, is approximately 220 million base pairs long.
In living organisms, DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together. These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. A base linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. If multiple nucleotides are linked together, as in DNA, this polymer is called a polynucleotide.
The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are called the 5′ (five prime) and 3′ (three prime) ends, 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 alternative pentose sugar ribose in RNA.
The DNA double helix is stabilized by hydrogen bonds between the bases attached to the two strands. The four bases found in DNA are adenine (abbreviated 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.
These bases are classified into two types; adenine and guanine are fused five- and six-membered heterocyclic compounds called purines, while cytosine and thymine are six-membered rings called pyrimidines. A fifth pyrimidine base, called uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. In addition to RNA and DNA, a large number of artificial nucleic acid analogues have also been created to study the proprieties of nucleic acids, or for use in biotechnology.
Twin helical strands form the DNA backbone. Another double helix may be found by tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.
Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.
The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, left). DNA with high GC-content is more stable than DNA with low GC-content, but contrary to popular belief, this is not due to the extra hydrogen bond of a GC base pair but rather the contribution of stacking interactions (hydrogen bonding merely provides specificity of the pairing, not stability).
As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.
In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.
Sense and antisense
A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.
A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.
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. 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. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.
Alternate DNA structures
DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.
The first published reports of A-DNA X-ray diffraction patterns— and also B-DNA used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then 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. In the same journal, James D. 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.
Although the `B-DNA form' is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.
Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.
Alternate DNA chemistry
For a number of 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 December 2010 NASA press conference revealed that the bacterium GFAJ-1, which has evolved in an arsenic-rich environment, is the first terrestrial lifeform found which may have this ability. The bacterium was found in Mono Lake, east of Yosemite National Park. GFAJ-1 is a rod-shaped extremophile bacterium in the family Halomonadaceae that, when starved of phosphorus, may be capable of incorporating the usually poisonous element arsenic in its DNA. This discovery lends weight to the long-standing idea that extraterrestrial life could have a different chemical makeup from life on Earth. The research was carried out by a team led by Felisa Wolfe-Simon, a geomicrobiologist and geobiochemist, a Postdoctoral Fellow of the NASA Astrobiology Institute with Arizona State University.
At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.
These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.
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. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.
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. For example, cytosine methylation, produces 5-methylcytosine, which is important for X-chromosome inactivation. 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. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.
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. 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. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.
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, daunomycin, and doxorubicin. In order 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. As a result, DNA intercalators are often carcinogens, and benzo[a]pyrene diol epoxide, acridines, aflatoxin and ethidium bromide are well-known examples. 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.
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. 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 alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions between DNA and other molecules that mediate the function of the genome.
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, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame.
In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma". However, DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.
Some non-coding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of non-coding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.
Transcription and translation
A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).
In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.
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. 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.
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.
Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.
A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.
In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.
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′-GAT|ATC-3′ and makes a cut at the vertical line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.
Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.
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. 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. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.
Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly ATP, to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.
Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are copies of existing polynucleotide chains - which are called templates. These enzymes function by adding nucleotides onto the 3′ hydroxyl group of the previous nucleotide in a DNA strand. As a consequence, all polymerases work in a 5′ to 3′ direction. 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, a DNA-dependent DNA polymerase makes a copy of a DNA sequence. Accuracy is vital in this process, so many of these 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. 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.
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. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.
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.
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". 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 during chromosomal crossover when they recombine. 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. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.
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. The first step in recombination is a double-stranded break either caused by an endonuclease or damage to the DNA. 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.
DNA contains the genetic information that allows all modern living things 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. 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. 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.
However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible. This is because DNA will survive in the environment for less than one million years and slowly degrades into short fragments in solution. 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, but these claims are controversial.
Uses in technology
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genetic material in a way that does not occur under natural conditions. It involves the use of recombinant DNA techniques, but does not include traditional animal and plant breeding or mutagenesis. Any organism that is generated using these techniques is considered to be a genetically modified organism. The first organisms genetically engineered were bacteria in 1973 and then mice in 1974. Insulin producing bacteria were commercialized in 1982 and genetically modified food has been sold since 1994.
Producing genetically modified organisms or tissues is a multi-step process. It first involves the isolating and copying the genetic material of interest; if necessary, changes to genetic sequence may be introduced. A construct may be built containing all the genetic elements for correct expression in a vector. This vector construct is then introduced into the host organism in a process called transformation, transfection or transduction. Successfully transformed organisms or tissues are then selectively grown, usually by growing material in conditions which require the presence of a gene in the inserted material for survival.
Genetic engineering techniques have been applied to various industries, with some success. Medicines such as insulin and human growth hormone are now produced in bacteria, experimental mice such as the oncomouse and the knockout mouse are being used for research purposes and insect resistant and/or herbicide tolerant crops have been commercialized. Plants that contain drugs and vaccines, animals with beneficial proteins in their milk and stress tolerant crops are currently being developed.
Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic 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. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.
People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents. On the other hand, many convicted people have been released from prison on the basis of DNA techniques, which were not available when a crime had originally been committed.
Bioinformatics involves the manipulation, searching, and data mining of biological data, and this includes DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory. 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. The DNA sequenced 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. 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. 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 uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based as well as using the "DNA origami" method) as well as three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.
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. 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; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.
DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of Sally Hemings and Thomas Jefferson. This usage is closely related to the use of DNA in criminal investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has matched relatives of the guilty individual.
History of DNA research
DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.
In 1928, Frederick Griffith discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic information—the Avery–MacLeod–McCarty experiment—when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the T2 phage.
In 1953, James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image (labeled as "Photo 51") taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases are paired — also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.
Experimental evidence supporting the Watson and Crick model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick model; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. However, Nobel rules of the time allowed only living recipients, but a vigorous debate continues on who should receive credit for the discovery.
In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.
- DNA microarray
- DNA sequencing
- Genetic disorder
- Junk DNA
- Molecular models of DNA
- Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
- Nucleic acid analogues
- Nucleic acid methods
- Nucleic acid modeling
- Nucleic acid notation
- Paracrystal model and theory
- X-ray crystallography
- X-ray scattering
- Polymerase chain reaction
- Proteopedia DNA
- Southern blot
- Triple-stranded DNA
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GFAJ-1 is a strain of rod-shaped bacteria in the family Halomonadaceae. The extremophile was isolated from the hypersaline and alkaline Mono Lake in eastern California by a research team led by NASA astrobiologist Felisa Wolfe-Simon. In a 2010 Science journal publication, the authors claimed that the microbe, when starved of phosphorus, is capable of substituting arsenic for a small percentage of its phosphorus and sustain its growth. Immediately after publication, other microbiologists and biochemists expressed doubt about this claim which was robustly criticized in the scientific community. Subsequent independent studies published in 2012 found no detectable arsenate in the DNA of GFAJ-1, refuted the claim, and demonstrated that GFAJ-1 is simply an arsenate-resistant, phosphate-dependent organism.
The GFAJ-1 bacterium was discovered by geomicrobiologist Felisa Wolfe-Simon, a NASA astrobiology fellow in residence at the US Geological Survey in Menlo Park, California. GFAJ stands for "Give Felisa a Job". The organism was isolated and cultured beginning in 2009 from samples she and her colleagues collected from sediments at the bottom of Mono Lake, California, U.S.A. Mono Lake is hypersaline (about 90 grams/liter) and highly alkaline (pH 9.8). It also has one of the highest natural concentrations of arsenic in the world (200 μM). The discovery was widely publicized on 2 December 2010.
Taxonomy and phylogeny
|Phylogeny of GFAJ-1 and closely related bacteria based on ribosomal DNA sequences.|
Molecular analysis based on 16S rRNA sequences shows GFAJ-1 to be closely related to other moderate halophile ("salt-loving") bacteria of the family Halomonadaceae. Although the authors produced a cladogram in which the strain is nested among members of Halomonas, including H. alkaliphila and H. venusta, they did not explicitly assign the strain to that genus. Many bacteria are known to be able to tolerate high levels of arsenic, and to have a proclivity to take it up into their cells. However, GFAJ-1 has now been proposed to go a step further; when starved of phosphorus, it may instead incorporate arsenic into its metabolites and macromolecules and continue growing.
Species or strain
In the Science journal article, GFAJ-1 is referred to as a strain of Halomonadaceae and not as a new species. The International Code of Nomenclature of Bacteria, the set of regulations which govern the taxonomy of bacteria, and certain articles in the International Journal of Systematic and Evolutionary Microbiology contain the guidelines and minimal standards to describe a new species, e.g. the minimal standards to describe a member of the Halomonadaceae. Organisms are described as new species if they meet certain physiological and genetic condition, such as generally less than 97% 16S rRNA sequence identity to other known species) and metabolic differences allowing them to be discerned apart. In addition to indicators to tell the novel species from other species, other analyses are required, such as fatty acid composition, respiratory quinone used and tolerance ranges and deposition of the strain in at least two microbiological repositories. New proposed names are given in italics followed by sp. nov. (and gen. nov. if it is a novel genus according to the descriptions of that clade). In the instance of the GFAJ-1 strain these criteria are not met, and the strain is not claimed to be a new species. When a strain is not assigned to a species (e.g. due to insufficient data or author choice) it is often labeled as the genus name followed by "sp." (i.e., undetermined species of that genus) and the strain name. In the case of GFAJ-1 the authors chose to refer to the strain by strain designation only. Strains closely related to GFAJ-1 include Halomonas sp. GTW and Halomonas sp. G27, neither of which were described as valid species. If the authors had formally assigned strain GFAJ-1 to the Halomonas genus, the name would be given as Halomonas sp. GFAJ-1.
A phosphorus-free growth medium (which actually contained 3.1 ± 0.3 μM of residual phosphate, from impurities in reagents) was used to culture the bacteria in a regime of increasing exposure to arsenate; the initial level of 0.1 mM was eventually ramped up to 40 mM. Alternative media used for comparative experiments contained either high levels of phosphate (1.5 mM) with no arsenate, or had neither added phosphate nor added arsenate. It was observed that GFAJ-1 could grow through many doublings in cell numbers when cultured in either phosphate or arsenate media, but could not grow when placed in a medium of a similar composition to which neither phosphate nor arsenate was added. The phosphorus content of the arsenic-fed, phosphorus-starved bacteria (as measured by ICP-MS) was only 0.019 (± 0.001) % by dry weight, one thirtieth of that when grown in phosphate-rich medium. This phosphorus content was also only about one tenth of the cells' average arsenic content (0.19 ± 0.25% by dry weight). The arsenic content of cells as measured by ICP-MS varies widely and can be lower than the phosphorus contents in some experiments, and up to fourteen times higher in others. Other data from the same study obtained with nano-SIMS suggest a ~75-fold excess of phosphate (P) over arsenic (As) when expressed as P:C and As:C ratios, even in cells grown with arsenate and no added phosphate. When cultured in the arsenate solution, GFAJ-1 only grew 60% as fast as it did in phosphate solution. The phosphate-starved bacteria had an intracellular volume 1.5 times normal; the greater volume appeared to be associated with the appearance of large "vacuole-like regions".
When the researchers added isotope-labeled arsenate to the solution to track its distribution, they found that arsenic was present in the cellular fractions containing the bacteria's proteins, lipids and metabolites such as ATP, as well as its DNA and RNA. Nucleic acids from stationary phase cells starved of phosphorus were concentrated via five extractions (one with phenol, three with phenol-chloroform and one with chloroform extraction solvent), followed by ethanol precipitation. Although direct evidence of the incorporation of arsenic into biomolecules is still lacking, radioactivity measurements suggested that approximately one-tenth (11.0 ± 0.1%) of the arsenic absorbed by these bacteria ended up in the fraction that contained the nucleic acids (DNA and RNA) and all other co-precipitated compounds not extracted by the previous treatments. A comparable control experiment with isotope-labeled phosphate was not performed. With the distribution of the strain in mid-2011, other labs began to independently test the validity of the discovery. Prof. Rosie Redfield from the University of British Columbia, following issues with the growth conditions, investigated the growth requirements of GFAJ-1, and found that the strain grows better on solid agar medium than in liquid culture. Redfield attributed this to low potassium levels and hypothesized that the potassium levels in basal ML60 medium may be too low to support growth. Redfield after finding and addressing further issues (ionic strength, pH and the use of glass tubes instead of polypropylene) found that arsenate marginally stimulated growth, but didn't affect the final densities of the cultures, unlike what was claimed. Subsequent studies using mass spectrometry by the same group found no evidence of arsenate being incorporated into the DNA of GFAJ-1.
Arsenate ester stability
Arsenate esters, such as those that would be present in DNA, are generally expected to be orders of magnitude less stable to hydrolysis than corresponding phosphate esters. dAMAs, the structural arsenic analog of the DNA building block dAMP, has a half-life of 40 minutes in water at neutral pH. Estimates of the half-life in water of arsenodiester bonds, which would link the nucleotides together, are as short as 0.06 seconds—compared to 30 million years for the phosphodiester bonds in DNA. The authors speculate that the bacteria may stabilize arsenate esters to a degree by using poly-β-hydroxybutyrate (which has been found to be elevated in "vacuole-like regions" of related species of the genus Halomonas) or other means to lower the effective concentration of water. Polyhydroxybutyrates are used by many bacteria for energy and carbon storage under conditions when growth is limited by elements other than carbon, and typically appear as large waxy granules closely resembling the "vacuole-like regions" seen in GFAJ-1 cells. The authors present no mechanism by which insoluble polyhydroxybutyrate may lower the effective concentration of water in the cytoplasm sufficiently to stabilize arsenate esters. Although all halophiles must reduce the water activity of their cytoplasm by some means to avoid desiccation, the cytoplasm always remains an aqueous environment.
NASA's announcement of a news conference "that will impact the search for evidence of extraterrestrial life" was criticized as sensationalistic and misleading; an editorial in New Scientist commented "although the discovery of alien life, if it ever happens, would be one of the biggest stories imaginable, this was light-years from that."
In addition, many experts who have evaluated the paper have concluded that the reported studies do not provide enough evidence to support the claims made by the authors. In an online article on Slate, science writer Carl Zimmer discussed the skepticism of several scientists: "I reached out to a dozen experts ... Almost unanimously, they think the NASA scientists have failed to make their case". Chemist Steven A. Benner has expressed doubts that arsenate has replaced phosphate in the DNA of this organism. He suggested that the trace contaminants in the growth medium used by Wolfe-Simon in her laboratory cultures are sufficient to supply the phosphorus needed for the cells' DNA. He believes that it is more likely that arsenic is being sequestered elsewhere in the cells. University of British Columbia microbiologist Rosemary Redfield said that the paper "doesn't present any convincing evidence that arsenic has been incorporated into DNA or any other biological molecule," and suggests that the experiments lacked the washing steps and controls necessary to properly validate their conclusions. Harvard microbiologist Alex Bradley said that arsenic-containing DNA would be so unstable in water it could not have survived the analysis procedure.
On 8 December 2010, Science published a response by Wolfe-Simon, in which she stated that criticism of the research was expected. In response, a "Frequently Asked Questions" page to improve understanding of the work was posted on 16 December 2010. The team plans to deposit the GFAJ-1 strain in the ATCC and DSMZ culture collections to allow widespread distribution. In late May 2011, the strain has also been made available upon request directly from the laboratory of the authors. Science has made the article freely available. The article was published in print six months after acceptance in the 3 June 2011 issue of Science. The publication was accompanied by eight technical comments addressing various concerns regarding the article's experimental procedure and conclusion, as well as a response by the authors to these concerns. The editor in chief has indicated that some issues remain and that their resolution is likely to be a long process. A review by Rosen et al., in the March 2011 issue of journal Bioessays, discusses the technical issues with the Science paper, provides alternative explanations, and highlights known biochemistry of other arsenic resistant and arsenic utilizing microbes.
On 27 May 2011, Wolfe-Simon and her team responded to the criticism in a follow-up Science journal publication. Then on January 2012 a group of researchers led by Rosie Redfield at the University of British Columbia analyzed the DNA of GFAJ-1 using liquid chromatography–mass spectrometry and could not detect any arsenic, which Redfield calls a "clear refutation" of the original paper's findings. Following the publication of the articles challenging the conclusions of the original Science article first describing GFAJ-1, the website Retraction Watch argued that the original article should be retracted because of misrepresentation of critical data.
- Arsenic biochemistry
- Arsenic poisoning
- Arsenic toxicity
- Hypothetical types of biochemistry
- Nucleic acid analogues
- Organoarsenic chemistry
- Prebiotic arsenic
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The family was originally described in 1988 to contain the genera Halomonas and Deleya.
In 1989, Chromobacterium marismortui was reclassified as Chromohalobacter marismortui forming a third genus in the family Halomonadaceae.
Subsequently, in 1990 a species was discovered and was originally proposed to be called Volcaniella eurihalina forming a new genus in the Halomonadaceae, but was later (in 1995) reclassified as a member of the genus Halomonas.
The species Carnimonas nigrificans (sole member of genus) was not placed in the family due to the lack of two out of 15 descriptive 16S rRNA signature sequences, but it has been proposed to reclassify it into the family.
In 1996, the family was later reorganised by unifying genera Deleya, Halomonas and Halovibrio and the species Paracoccus halodenitrificans into Halomonas and placing Zymobacter in this family. However, it was later discovered that the strain of Halovibrio variabilis DSM 3051 and DSM 3050 differed and the latter was made type strain of the Halovibrio, which remains still in use. and now comprising two species (the other being Halovibrio denitrificans)
In 2002, Halomonas marina was transferred to its own genus Cobetia, and in 2009 Halomonas marisflavi, Halomonas indalinina. and Halomonas avicenniae were transferred to a new genus called Kushneria (5 species)
Several singleton genera were created recently: in 2007, Halotalea alkalilenta was described, Aidingimonas halophila in 2009, Halospina denitrificans in 2006, Modicisalibacter tunisiensis in 2009 Salinicola socius in 2009. To the latter genus two species were transferred Halomonas salaria as Salinicola salarius and Chromohalobacter salarius as Salinicola halophilus.
- Halomonas, the type genus
- Aidingimonas halophila 
- Chromohalobacter marismortui
- Chromohalobacter beijerinckii
- Chromohalobacter canadensis and Chromohalobacter israelensis, formerly of the genus Halomonas
- Chromohalobacter japonicus
- Chromohalobacter nigrandesensis
- Chromohalobacter salarius
- Chromohalobacter salexigens
- Chromohalobacter sarecensis, phychrotolerant
- Halotalea alkalilenta
- Kushneria aurantia, type species
- Kushneria marisflavi, Kushneria indalinina and Kushneria avicenniae were previously classified under Halomonas
- Zymobacter, not to be confused with Zymomonas mobilis, an alphaproteobacterion studies for its biofuel production, an easy error that even the International Code of Nomenclature of Bacteria made in  as noted in 
Note: Species of Deleya and Halovibrio are now now Halomonas
The names derives from Halomonas, which is the type genus of the family, plus the suffix -aceae, ending to denote a family
Geomicrobiologist Felisa Wolfe-Simon with a NASA funded team is researching a particular strain the Halomonadaceae family, named GFAJ-1, isolated and cultured from sediments collected along the shore of Mono Lake, near Yosemite National Park in eastern California. This GFAJ-1 strain of Halomonadaceae can grow in the presence of high concentrations of arsenic.
- FRANZMANN (P.D.), WEHMEYER (U.) and STACKEBRANDT (E.): Halomonadaceae fam. nov., a new family of the class Proteobacteria to accommodate the genera Halomonas and Deleya. Syst. Appl. Microbiol., 1988, 11, 16-19.
- VENTOSA (A.), GUTIERREZ (M.C.), GARCIA (M.T.) and RUIZ-BERRAQUERO (F.): Classification of "Chromobacterium marismortui" in a new genus, Chromohalobacter gen. nov., as Chromohalobacter marismortui comb. nov., nom. rev. Int. J. Syst. Bacteriol., 1989, 39, 382-386.
- QUESADA (E.), VALDERRAMA (M.J.), BEJAR (V.), VENTOSA (A.), GUTIERREZ (M.C.), RUIZ-BERRAQUERO (F.) and RAMOS-CORMENZANA (A.): Volcaniella eurihalina gen. nov., sp. nov., a moderately halophilic nonmotile gram-negative rod. Int. J. Syst. Bacteriol., 1990, 40, 261-267
- Mellado, E., Moore, E. R. B., Nieto, J. J. & Ventosa, A. (1995). Phylogenetic inferences and taxonomic consequences of 16S. ribosomal DNA sequence comparison of Chromohalobacter marismortui, Volcaniella eurihalina, and Deleya salina and reclassification of V. eurihalina as Halomonas eurihalina comb. nov. Int J Syst Bacteriol 45, 712–716.
- Garriga, M.; Ehrmann, M. A.; Arnau, J.; Hugas, M.; Vogel, R. F. (1998). "Carnimonas nigrificans gen. nov., sp. nov., a bacterial causative agent for black spot formation on cured meat products". International Journal of Systematic Bacteriology 48: 677. doi:10.1099/00207713-48-3-677. PMID 9734022.
- D. R. Arahal, W. Ludwig, K. H. Schleifer and A. Ventosa Phylogeny of the family Halomonadaceae based on 23S and 16S rDNA sequence analyses. International Journal of Systematic and Evolutionary Microbiology, Vol 52, 241-249
- DOBSON (S.J.) and FRANZMANN (P.D.): Unification of the genera Deleya (Baumann et al. 1983), Halomonas (Vreeland et al. 1980), and Halovibrio (Fendrich 1988) and the species Paracoccus halodenitrificans (Robinson and Gibbons 1952) into a single genus, Halomonas, and placement of the genus Zymobacter in the family Halomonadaceae. Int. J. Syst. Bacteriol., 1996, 46, 550-558
- Sorokin, D. Y.; Tindall, B. J. (2006). "The status of the genus name Halovibrio Fendrich 1989 and the identity of the strains Pseudomonas halophila DSM 3050 and Halomonas variabilis DSM 3051. Request for an Opinion". International Journal of Systematic and Evolutionary Microbiology 56 (2): 487–489. doi:10.1099/ijs.0.63965-0.
- Sorokin, D. Y.; Tourova, T. P.; Galinski, E. A.; Belloch, C.; Tindall, B. J. (2006). "Extremely halophilic denitrifying bacteria from hypersaline inland lakes, Halovibrio denitrificans sp. nov. And Halospina denitrificans gen. nov., sp. nov., and evidence that the genus name Halovibrio Fendrich 1989 with the type species Halovibrio variabilis should be associated with DSM 3050". International Journal of Systematic and Evolutionary Microbiology 56 (2): 379. doi:10.1099/ijs.0.63964-0.
- ARAHAL (D.R.), CASTILLO (A.M.), LUDWIG (W.), SCHLEIFER (K.H.) and VENTOSA (A.): Proposal of Cobetia marina gen. nov., comb. nov., within the family Halomonadaceae, to include the species Halomonas marina. Syst. Appl. Microbiol., 2002, 25, 207-211.
- Ntougias, S.; Zervakis, G. I.; Fasseas, C. (2007). "Halotalea alkalilenta gen. Nov., sp. Nov., a novel osmotolerant and alkalitolerant bacterium from alkaline olive mill wastes, and emended description of the family Halomonadaceae Franzmann et al. 1989, emend. Dobson and Franzmann 1996". International Journal of Systematic and Evolutionary Microbiology 57 (9): 1975–1983. doi:10.1099/ijs.0.65078-0.
- Wang, Y.; Tang, S. -K.; Lou, K.; Lee, J. -C.; Jeon, C. O.; Xu, L. -H.; Kim, C. -J.; Li, W. -J. (2009). "Aidingimonas halophila gen. Nov., sp. Nov., a moderately halophilic bacterium isolated from a salt lake". International Journal of Systematic and Evolutionary Microbiology 59 (12): 3088–3094. doi:10.1099/ijs.0.010264-0.
- Ben Ali Gam, Z.; Abdelkafi, S.; Casalot, L.; Tholozan, J. L.; Oueslati, R.; Labat, M. (2007). "Modicisalibacter tunisiensis gen. nov., sp. nov., an aerobic, moderately halophilic bacterium isolated from an oilfield-water injection sample, and emended description of the family Halomonadaceae Franzmann et al. 1989 emend Dobson and Franzmann 1996 emend. Ntougias et al. 2007". International Journal of Systematic and Evolutionary Microbiology 57 (10): 2307. doi:10.1099/ijs.0.65088-0.
- ANAN'INA (L.N.), PLOTNIKOVA (E.G.), GAVRISH (E.Y.), DEMAKOV (V.A.) and EVTUSHENKO (L.I.): Salinicola socius gen. nov., sp. nov., a moderately halophilic bacterium from a naphthalene-utilizing microbial association. Microbiology, 2007, 76, 324-330 (translation of Mikrobiologiya, 2007, 76, 369-376).
- De La Haba, R. R.; Sanchez-Porro, C.; Marquez, M. C.; Ventosa, A. (2009). "Taxonomic study of the genus Salinicola: Transfer of Halomonas salaria and Chromohalobacter salarius to the genus Salinicola as Salinicola salarius comb. Nov. And Salinicola halophilus nom. Nov., respectively". International Journal of Systematic and Evolutionary Microbiology 60 (4): 963–971. doi:10.1099/ijs.0.014480-0.
- Thao, M. L.; Baumann, P. (2004). "Evolutionary Relationships of Primary Prokaryotic Endosymbionts of Whiteflies and Their Hosts". Applied and Environmental Microbiology 70 (6): 3401–3406. doi:10.1128/AEM.70.6.3401-3406.2004. PMC 427722. PMID 15184137.
- VREELAND (R.H.), LITCHFIELD (C.D.), MARTIN (E.L.) and ELLIOT (E.): Halomonas elongata, a new genus and species of extremely salt-tolerant bacteria. Int. J. Syst. Bacteriol., 1980, 30, 485-495
- ROBINSON (J.) and GIBBONS (N.E.): The effect of salts on the growth of Micrococcus halodentrificans n. sp. Canadian Journal of Botany, 1952, 30, 147-154
- Elazari-Volcani 1940
- Hof 1935
- WANG (Y.), TANG (S.K.), LOU (K.), LEE (J.C.), JEON (C.O.), XU (L.H.), KIM (C.J.) and LI (W.J.): Aidingimonas halophila gen. nov., sp. nov., a moderately halophilic bacterium isolated from a salt lake. Int. J. Syst. Evol. Microbiol., 2009, 59, 3088-3094
- COBET (A.B.), WIRSEN (C.) and JONES (G.E.): The effect of nickel on a marine bacterium, Arthrobacter marinus sp. nov. Journal of General Microbiology, 1970, 62, 159-169.
- KIM (M.S.), ROH (S.W.) and BAE (J.W.): Cobetia crustatorum sp. nov., a novel slightly halophilic bacterium isolated from traditional fermented seafood in Korea. Int. J. Syst. Evol. Microbiol., 2010, 60, 620-626.
- NTOUGIAS (S.), ZERVAKIS (G.I.) and FASSEAS (C.): Halotalea alkalilenta gen. nov., sp. nov., a novel osmotolerant and alkalitolerant bacterium from alkaline olive mill wastes, and emended description of the family Halomonadaceae Franzmann et al. 1989
- SÁNCHEZ-PORRO (C.), DE LA HABA (R.R.), SOTO-RAMÍREZ (N.), MÁRQUEZ (M.C.), MONTALVO-RODRÍGUEZ (R.) and VENTOSA (A.): Description of Kushneria aurantia gen. nov., sp. nov., a novel member of the family Halomonadaceae, and a proposal for reclassification of Halomonas marisflavi as Kushneria marisflavi comb. nov., of Halomonas indalinina as Kushneria indalinina comb. nov. and of Halomonas avicenniae as Kushneria avicenniae comb. nov. Int. J. Syst. Evol. Microbiol., 2009, 59, 397-405.
- Arahal, D. R.; Vreeland, R. H.; Litchfield, C. D.; Mormile, M. R.; Tindall, B. J.; Oren, A.; Bejar, V.; Quesada, E.; Ventosa, A. (2007). "Recommended minimal standards for describing new taxa of the family Halomonadaceae". International Journal of Systematic and Evolutionary Microbiology 57 (Pt 10): 2436–2446. doi:10.1099/ijs.0.65430-0. PMID 17911321.
- Arahal, DR; Vreeland, RH; Litchfield, CD, et al. Errata. Recommended minimal standards for describing new taxa of the family Halomonadaceae (vol 57, pg 2436, 2007) Int. J. Syst. Evol. Microbiol., 58, 2673-2673, 2008
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