History And Background Of Dna

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02 Nov 2017

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DNA

Acronym for d eoxyribo n ucleic a cid, a type of nucleic acid that serves as the carrier of heredity in cellular organisms and in many kinds of viruses. DNA is often referred to as "the genetic blueprint for life." Nucleic acid molecules are chains of nucleotides, which are compounds consisting of three subunits: a sugar, a nitrogen-containing base, and a phosphate group (see Phosphoric Acid). In DNA, the sugar is deoxyribose. Four nitrogenous bases are found in DNA: adenine, guanine, thymine, and cytosine. DNA commonly takes the form of an extremely long, double helix composed of two intertwining helical strands of nucleotides. Each strand is linked to the other by hydrogen bonds between the bases--somewhat like the rungs of a twisting rope ladder. In eukaryotes (cellular organisms whose cells have a distinct nucleus), DNA is found mainly in the cell nucleus, where, usually linked with protein, it accounts for a major part of chromosomes, but DNA also occurs outside the nucleus in the small bodies, or organelles (see Cell), known as mitochondria, which produce energy, and chloroplasts, which are the site of photosynthesis in plants. In prokaryotes, single-celled organisms (such as bacteria) that lack a distinct nucleus (meaning no nuclear membrane surrounds the DNA), the genetic material is in the form of one or more chromosomes that may be circular or linear double strands; in addition to this chromosomal DNA, there may be one or more shorter circular or linear DNA structures called plasmids.

Replication and Transcription

The genetic information carried by DNA is manifested through the sequence in which the four nitrogen-containing bases occur. This genetic code guides such essential functions as the replication of DNA and the synthesis of proteins needed by the body. The key to DNA's ability to preserve and transmit genetic information is that the bases connecting the two strands of the double helix can bind together only in specific ways. Adenine links up only with thymine, and thymine only with adenine; guanine links up only with cytosine, and cytosine only with guanine. If a nucleotide on one strand has the base thymine, the other strand at the corresponding point can have only adenine; the situation is the same with cytosine and guanine. In other words, the two strands are complementary; each is sufficient to define the other.

DNA replicates by splitting into two separate single strands; each single strand functions as a template for the synthesis of a new partner strand from nucleotides in the neighborhood, which are assembled into a chain with the help of enzymes. Because of the constraint on the linking of bases, the new strand will be an identical copy of the original partner strand.

DNA guides the synthesis of proteins through a process known as transcription. A protein consists of one or more polypeptides, which are long chains of amino acids. The sequence of amino acids in a polypeptide chain is governed by the sequence of bases in the controlling DNA. A particular amino acid is specified by a specific triplet, or group of three bases, which is known as a codon. Thus, the amino acid leucine results from the codon guanine, adenine, and cytosine, and the amino acid valine is prescribed by the codon cytosine, adenine, and guanine. A DNA segment 300 nucleotides long is needed to specify a polypeptide consisting of 100 amino acids. A segment of DNA that codes for the cell's synthesis of a specific polypeptide or other product is called a structural gene. There also are regulatory genes which serve to switch one or more structural genes on or off.

Transcription makes use of ribonucleic acid, or RNA, to carry the polypeptide information to a ribosome, a site outside the cellular nucleus at which polypeptides are synthesized. The structure of RNA is much like that of DNA, except that the sugar in RNA is a ribose and the base uracil occurs instead of thymine. In transcription, a strand of DNA acts as a template for synthesis, again with the help of enzymes, of a single strand of RNA, which, as a result of the constraint on pairing of bases (uracil binds only with adenine; cytosine only with guanine), will be complementary to the template. This new strand is a type of RNA known as messenger RNA (mRNA). It travels from the nucleus to the ribosome, to which amino acids are ferried by a different variety of RNA, known as transfer RNA (tRNA). The mRNA directs, in a process known as translation, the assembly of amino acids into the specified polypeptide.

Historical Highlights

Nucleic acids were discovered in the 19th century, but not until 1944 was DNA found to be the carrier of genetic information, in an experiment by the Canadian-American bacteriologist Oswald T. Avery and his colleagues at the Rockefeller Institute in New York City. Confirmation came in a 1952 experiment by the American geneticists Alfred Hershey and Martha Chase (1927-2003) with bacteriophages (in short, "phages")--viruses that infect bacteria, altering the bacteria's genetic information so they produce new phages. Hershey (a cowinner of the 1969 Nobel Prize in physiology or medicine) and Chase found (1952) that when the DNA of the bacteriophage and protein coat were separated, the DNA by itself still caused infection, indicating that the DNA, rather than protein, is the genetic material of the bacteriophage. The following year the British biophysicist Francis Crick and the American biochemist James Watson, making use of X-ray diffraction studies carried out by the British biophysicists Maurice Wilkins and Rosalind Franklin, discovered the structure of DNA--two helical chains linked by bases--which provided a foundation for understanding how DNA could replicate itself and direct the synthesis of polypeptides. This breakthrough opened the way for modern molecular biology and a broad range of advances in applied science, running the gamut from genetically engineered crops, to new medical treatments and diagnostic techniques, to DNA fingerprinting. Crick, Watson, and Wilkins received the 1962 Nobel Prize in physiology or medicine. (Franklin's death in 1958 made her ineligible for a Nobel Prize as they are not awarded posthumously.)

Among many subsequent Nobel Prize-winning achievements, in 1956 the American biochemist Arthur Kornberg (cowinner with Severo Ochoa, 1959 Nobel Prize in physiology or medicine) discovered DNA polymerase, an enzyme that catalyzes, or promotes, the linking of nucleotides into long DNA polymers. Kornberg synthesized a form of DNA from "off-the-shelf" substances, but it was not biologically active; in 1967 he and colleagues succeeded in producing biologically active DNA from relatively simple chemicals. In the early 1960s the U.S. biochemists Robert William Holley, Marshall Warren Nirenberg, and Har Gobind Khorana (the three shared the 1969 Nobel Prize in physiology or medicine) showed how code carried in DNA can direct, with the help of RNA, the synthesis of proteins. In the early 1970s the U.S. biochemist Paul Berg (cowinner, 1980 Nobel Prize in chemistry) combined DNA from one organism with the DNA of another, marking the beginning of so-called recombinant DNA technology. A major step forward in DNA research and the practical application thereof was the 1983 invention by the American molecular biologist Kary Mullis (cowinner, 1993 Nobel Prize in chemistry) of the polymerase chain reaction (PCR), a technique that uses the enzyme DNA polymerase to quickly produce large numbers of copies of specific DNA fragments.

DNA Sequencing

Considerable effort has been devoted to determining the order of the bases in the DNA of various organisms. This process, known as sequencing, was extremely laborious and slow. The first organism to have its entire genome, or full set of DNA, sequenced was a type of bacteriophage, by the British biochemist Frederick Sanger in 1977 using a method he devised himself. The phage's genome consisted of 5386 bases. (Sanger's achievement earned him a share of the 1980 Nobel Prize in chemistry; he had previously received the prize, in 1958, for establishing the structure of insulin.) With improvements in techniques and equipment toward the end of the century, it became feasible to sequence more complex organisms within a reasonably short time frame. The first complete genome of a single-celled organism, the bacterium Haemophilus influenzae, was achieved by the American molecular biologist J. Craig Venter (1946- ) in 1995. The sequencing of the genome of the yeast Saccharomyces cerevisiae was completed the following year. In 1998, scientists for the first time sequenced the complete genome of a multicellular organism, the roundworm Caenorhabditis elegans. The first plant to be sequenced was the weed Arabidopsis thaliana in 2000.

An international effort to sequence the entire human genome, which contains some 3 billion base pairs, in 24 chromosomes, got under way in 1990. Progress toward the ultimate goal--to "find all the genes on every chromosome in the body and to determine their biochemical nature"--was expected to yield advances in the understanding and treatment of a broad variety of genetic and other disorders. Progress came faster than expected owing to technological advances and to a sequencing competition that developed between the international Human Genome Project and the private company Celera Genomics, headed by Venter, which used a different technique. The two groups finished a rough working draft of the sequence of base pairs by 2000 and achieved a virtually complete sequence by 2003. The following year genome project researchers reported that their analysis indicated the number of human genes was probably between 20,000 and 25,000.



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