Dictionary:

deoxyribonucleic acid

  (dē-ŏk'sē-rī'bō-nū-klē'ĭk, -klā'-, -nyū-)

DNA.

The material that carries genetic information in all organisms, except for some families of viruses that use ribonucleic acid (RNA). The set of DNA molecules that contains all genetic information for an organism is called its genome. DNA is found primarily in the nuclei of eukaryotic cells and in the nucleoid of bacteria. Small amounts of DNA are also found in mitochondria and chloroplasts and in autonomously maintained DNAs called plasmids. See also Nucleic acid.

DNA is composed of two long polymer strands of the sugar 2-deoxyribose, phosphate, and purine and pyrimidine bases. The backbone of each strand is composed of alternating 2-deoxyribose and phosphate linked together through phosphodiester bonds. A DNA strand has directionality; each phosphate is linked to the 3′ position of the preceding deoxyribose and to the 5′ position of the following deoxyribose (Fig. 1). The four bases found in DNA are adenine, thymine, guanine, and cytosine. Each 2-deoxyribose is linked to one of the four bases via a covalent glycosidic bond, forming a nucleotide. The sequence of these four bases allows DNA to carry genetic information. Bases can form hydrogen bonds with each other. Adenine forms two bonds with thiamine, and cytosine forms three bonds with guanine. These two sets of base pairs have the same geometry, allowing DNA to maintain the same structure regardless of the specific sequence of base pairs. See also Deoxyribose; Purine; Pyrimidine.

Diagram of the nucleic acid backbone, a repeating sugar-phosphate polymer chain with base side chains. The two chains are antiparallel, as shown by arrows. The dots between the bases represent hydrogen bonding. Although the chains are drawn flat, they are actually wound around each other in the molecule.

Structure

DNA is composed of two strands that wrap around each other to form a double helix. The two strands are held together by base pairing and are antiparallel. Thus if one strand is oriented in the 5′ to 3′ direction, the other strand will be 3′ to 5′. This double-helical structure of DNA was first proposed in 1954 by J. D. Watson and F. H. C. Crick. The most common form of DNA is the B-form, which is a right-handed double helix with 10.4 base pairs per turn. Less common forms of DNA include A-form, which is a right-handed double helix that has 11 base pairs per turn and has wider diameter than B-form, and Z-form, which is a narrow, irregular left-handed double helix.

For cells to live and grow, the genetic information in DNA must be (1) propagated and maintained from generation to generation, and (2) expressed to synthesize the components of a cell. These two functions are carried out by the processes of DNA replication and transcription, respectively. See also Genetic code.

Replication

Each of the two strands of a DNA double helix contains all of the information necessary to make a new double-stranded molecule. During replication the two parental strands are separated, and each is used as a template for the synthesis of a new strand of DNA. Synthesis of the nascent DNA strands is carried out by a family of enzymes called DNA polymerases. Base incorporation is directed by the existing DNA strand; nucleotides that base-pair with the template are added to the nascent DNA strand. The product of replication is two complete double-stranded helices, each of which contains all of the genetic information (has the identical base sequence) of the parental DNA. Each progeny double helix is composed of one parental and one nascent strand. DNA replication is very accurate. In bacteria the mutation rate is about 1 error per 1000 bacteria per generation, or about 1 error in 10⁹ base pairs replicated. This low error rate is due to a combination of the high accuracy of the replication process and cellular pathways which repair misincorporated bases. See also Mutation.

Transcription

In transcription, DNA acts as a template directing the synthesis of RNA. RNA is single-stranded polymer similar to DNA except that it contains the sugar ribose instead of 2-deoxyribose and the base uracil instead of thymidine. The two strands of DNA separate transiently, and one of the two single-stranded regions is used as a template to direct the synthesis of an RNA strand. As in DNA replication, base pairing between the incoming ribonucleotide and the template strand determines the sequence of bases incorporated into the nascent RNA. Thus, genetic information in the form of a specific sequence of bases is directly transferred from DNA to RNA in transcription. After the RNA is synthesized, the DNA reverts to double-stranded form. Transcription is carried out by a family of enzymes called RNA polymerases. Following transcription, newly synthesized RNA is often processed prior to being used to direct protein synthesis by ribosomes in a process called translation. See also Protein; Ribonucleic acid (RNA); Ribosomes.

Genetic variation

There is a great deal of variation in the DNA content and sequences in different organisms. Because of base pairing, the ratios of adenine to thiamine and cytosine to guanine are always the same. However, the ratio of adenine and thymine to guanine and cytosine in different organisms ranges from 25 to 75%. There is also large variation in the amount of DNA in the genome of various organisms. The simplest viruses have genomes of only a few thousand base pairs, while complex eukaryotic organisms have genomes of billions of base pairs. This variation partially reflects the increasing number of genes necessary to encode more complex organisms, but mainly reflects an increase in the amount of DNA that does not encode proteins (known as introns). A large percentage of the DNA in multicellular eukaryotes is in introns or is repetitive DNA (sequences that are repeated many times). In most eukaryotes the DNA sequences that encode proteins (known as exons) are not continuous but have introns interspersed within them. The initial transcript synthesized by RNA polymerase contains both exons and introns and can be many times the length of the actual coding sequence. The RNA is then processed and the introns are removed through a mechanism called RNA splicing to yield messenger RNA (mRNA), which is translated to make protein.

Recombinant technology

Techniques have been developed to allow DNA to be manipulated in the laboratory. These techniques have led to a revolution in biotechnology. This revolution began when methods were developed to cleave DNA at specific sequences and to join pieces of DNA together. Another major component of this technology is the ability to determine the sequence of the bases in DNA. There are two general approaches for determining DNA sequence. Either chemical reactions are carried out which specifically cleave the sugar-phosphate bond at sites which contain a certain base, or DNA is synthesized in the presence of modified bases that cause termination of synthesis after the incorporation of a certain base. These methods can now be automated so that it is practical to determine the DNA sequences of the entire genome of an organism. Currently, the complete sequences of several bacterial and fungal genomes are known, drafts exist for the complete mouse and rat genomes, and 99% of the gene-containing part of the human sequence has been determined. See also Human Genome Project.

In the cell

The full genome of DNA must be substantially compacted to fit into a cell. For example, the full human genome has a total length of about 3 m (10 ft). This DNA must fit into a nucleus with a diameter of 10⁻⁵ m. This immense reduction in length is accomplished in eukaryotes via multiple levels of compaction in a nucleoprotein structure termed chromatin. The first level involves spooling about 200 base pairs of DNA onto a complex of basic proteins called histones to form a nucleosome. Nucleosomes are connected like beads on a string to form a 10-nanometer diameter fiber, and this is further coiled to form a 30-nm fiber. The 30-nm fibers are further coiled and organized into loops formed by periodic attachments to a protein scaffold. This scaffold organizes the complex into the shape of the metaphase chromosome seen at mitosis. See also Nucleoprotein.

The nucleosome is the fundamental structural unit of DNA in all eukaryotes. Nucleosomes reduce the accessibility of the DNA to DNA-binding proteins such as polymerases and other protein factors essential for transcription and replication. Consequently, nucleosomes tend to act as general repressors of transcription. See also Nucleosome.

An organic chemical that carries genetic information found in the nucleus of all cells, and which is inherited from parents to offspring. The genetic information determines which proteins can be synthesized by each cell. These proteins include enzymes that determine the inherited characteristics of an individual. It is possible that as we age, DNA becomes damaged by intrinsic or extrinsic factors. This may lead to errors in the synthesis of various proteins, contributing to age-related degeneration in physical performance.

A nucleic acid occurring in cells as the basic structure of the genes. DNA is present in all body cells of every species, including unicellular organisms and DNA viruses. The structure of DNA was first described in 1953 by J.D. Watson and F.H.C. Crick.
DNA molecules are long linear polymers of small molecules called nucleotides, each of which consists of one molecule of the five-carbon sugar deoxyribose bonded to a phosphate group and to one of four heterocyclic nitrogenous compounds referred to as bases. A single strand of DNA is made by linking the nucleotides together in a chain with bonds between the sugar and phosphate groups of adjacent nucleotides. It thus consists of a backbone of alternating sugar and phosphate groups with a base attached to each sugar as a side chain. The four bases are two purines, adenine (A) and guanine (G), and two pyrimidines, cytosine (C) and thymine (T). Single-stranded DNA can be synthesized with any specified sequence of bases, but in living cells the base sequence has a meaning; it specifies the amino acid sequence of all of the polypeptides and proteins made by the cell. And since all of the enzymes that catalyze biochemical reactions are proteins, the DNA contains the specifications for all of the biochemistry and structure of the cell.
The chemical basis of the genetic code lies in the ability of the bases to form hydrogen bonds with each other. Unlike the covalent bonds holding together the atoms of a single strand of DNA, hydrogen bonds are weak and easily broken and reformed. Hydrogen bonding is governed by the base pairing rule: A always bonds with T, and C always bonds with G. A and T (or C and G) are called complementary bases. The genetic information is read and preserved by the matching up of complementary bases.
In cells, the DNA is double-stranded. The configuration of the DNA molecule resembles a ladder in which the sides are the sugar–phosphate backbones, which are antiparallel (they run in opposite directions), and the rungs are hydrogen-bonded complementary bases; thus, the entire sequence along the two strands is complementary. This whole structure is twisted so that the two strands form a double helix. Once before each cell division, a group of proteins splits the two strands apart, and as complementary nucleotides bond to the bases of each strand they are jointed to form a new strand. This process is called replication. It results in the exact duplication of the DNA molecule, because each strand serves as a template (pattern) for the synthesis of its complementary strand. When the cell divides, one copy goes to each daughter cell. Thus, the genetic information is passed on from generation to generation without change except for rare mutations, which result from copying errors or incorrectly repaired breaks in the DNA molecule that change the base sequence.
The reading of the genetic code involves two processes: transcription and translation. In transcription, a length of DNA is used as a template to make a complementary strand of messenger RNA (mRNA). RNA (ribonucleic acid) is a nuceic acid like DNA. The only differences are that the sugar, ribose, has an extra oxygen atom, and the pyrimidine base, uracil (U), which also pairs with adenine, replaces thymine. In translation, the mRNA molecule is read by a structure called a ribosome, which produces the polypeptide specified by the mRNA message.
The genetic code is a triplet code. Every triplet of bases along the strand specifies a single amino acid. There are 64 possible triplets (codons) that can be formed from the four bases. Each one specifies that one of 20 different amino acids be inserted in a growing polypeptide chain or marks either the start or the end of a chain.
Two other types of RNA are involved in translation. Ribosomal RNA (rRNA) forms a large part of the ribosome. Transfer RNA (tRNA) is the means by which codons are matched with amino acids. tRNAs are small molecules with several self-complementary sections so that they fold up into a compact structure owing to bonding between complementary bases. One end of the molecule is a three-base anticodon, which bonds to its complementary codon on mRNA molecules. The other end is recognized by a specific enzyme which attaches the correct amino acid to it. During translation, the ribosome proceeds along the mRNA molecule and, as each codon is matched by a specific tRNA, the amino acid it carries is transferred to the growing polypeptide chain, and the process is repeated until the ‘stop’ codon is reached. Like the mRNA molecules, rRNA and tRNA molecules are formed on DNA templates; the genetic material contains not only the information for polypeptide sequences but also for rRNA and tRNA sequences.
The chromosomes of mammalian cells contain 3 × 10⁹ base pairs which is enough to code for the 100,000 or so enzymes and structural proteins. Less than 10% of the DNA codes for proteins and RNA, the rest is noncoding, also referred to as ‘junk’ DNA, and is of uncertain purpose. DNA is the molecule that directs all of the activities of living cells, including its own reproduction and perpetuation in generation after generation.