Nucleic Acids

Nucleic acids are a family of macromolecules that includes deoxyribonucleic acid (DNA ) and multiple forms of ribonucleic acid (RNA ). DNA, in humans and most organisms, is the genetic material and represents a collection of instructions (genes) for making the organism. This collection of instructions is called the genome of the organism. The primary classes of RNA molecules either provide information that is used to convert the genetic information in DNA into functional proteins, or are important players in the translational process , in which the actual process of protein synthesis (on ribosomes ) occurs.

Discovery of and Evidence for DNA as the Genetic Material

DNA was first discovered in 1869 by a Swiss biochemist, Johann Friedrich Miescher. He extracted a gelatinous material that contained organic phosphorus from cells in human pus that was obtained from the bandages of wounded soldiers. He named this material nuclein. Ten years later Albrecht Kossel explored the chemistry of nuclein (for which he received the Nobel Prize) and discovered that it contained the organic bases adenine , thymine , guanine , and cytosine . In 1889 Richard Altman removed the proteins from the nuclein in yeast cells and named the deproteinized material nucleic acid. It was not until about 1910 that it was realized that there were two types of nucleic acid, DNA and RNA. A great deal of chemistry during the early part of the twentieth century focused on characterizing the composition of and the linkages in both DNA and RNA. A chemical test for deoxyribose, developed by Robert Feulgen during the 1920s, was the first test capable of distinguishing DNA from RNA. Because of the simplicity of the composition of DNA, which has only four bases (and early reports indicated erroneously that there were equimolar quantities of each), it was originally thought that DNA molecules functioned in chromosomal stability and maintenance. It was only after Erwin Chargaff, in 1950, showed that the molar amounts of the bases varied widely in different organisms that the notion that DNA might be the genetic material became an attractive idea.

The general consensus prior to the mid-1940s was that proteins (which contain twenty different amino acids) were the most logical candidate for the genetic material. Three later, however, findings pointed toward the conclusion that DNA was the genetic material. During the 1920s Frederick Griffith examined the activity of cell extracts in an attempt to identify a "transforming principle" (and a specific molecule related to this principle) in experiments with the bacterium Streptococcus pneumoniae. Unfortunately, his experiments failed to identify a specific molecule. In 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty partially purified cell extracts and presented evidence that the genetic component of these cells was DNA. In 1952 Alfred Hershey and Martha Chase investigated the infection of Escherichia coli cells with phage T2 (a virus) and their results were further corroboration that DNA was the genetic material. Since that time, a large body of evidence has confirmed the (nearly) universal truth that DNA is the genetic, heritable material in organisms. (The only exception to this is the case of RNA viruses, such as the AIDS virus, in which RNA is the only nucleic acid present in the virus and the genetic material.)

Modern research took a giant step forward when James Watson and Francis Crick, analyzing the collected findings of a number of laboratories, proposed the double helix structure of DNA in 1953. Their announcements motivated scientists to find corroboration for this proposal. During the 1980s detailed x-ray crystallographic analyses of DNA became acknowledged as proof of the structural arrangement that had been described by Watson and Crick, including the Watson–Crick complementary base-pairing arrangements. The elucidation of the structure of DNA led to an enormous and rapid expansion of our understanding of DNA's function in the living cell.

Types of Nucleic Acids: Composition and Structure

All nucleic acids are linear, nonbranching polymers of nucleotides, and are therefore polynucleotides. DNA is double-stranded in virtually all organisms. (It is single-stranded in some viruses.) DNA occurs in many, but not all, small organisms as double-stranded and circular (without any ends). Higher organisms (eukaryotes) have approximately ten million base pairs or more, with the genetic material parceled out into multiple genetic pieces called chromosomes. For example, humans have twenty-three pairs of chromosomes in the nucleus of each somatic cell . Within the nucleus, the DNA molecules are found in "looped arrangements" that mimic the circular DNA observed in many prokaryotes.

All RNA molecules are single-stranded molecules. RNA molecules are synthesized from DNA templates in a process known as transcription ; these molecules have a number of vital roles within cells. It is convenient to divide RNA molecules into the three functional classes, all of which function in the cytoplasm.

Messenger RNA (mRNA) contains the information (formerly residing in DNA) that is decoded in a way that enables the manufacture of a protein, and migrates from the nucleus to ribosomes in the cytoplasm (where proteins are assembled). A triplet of nucleotides within an RNA molecule (called a codon) specifies the amino acid to be incorporated into a specific site in the protein being assembled. A cell's population of mRNA molecules is very diverse, as these molecules are responsible for the synthesis of the many different proteins found in the cell. However, mRNA makes up only 5 percent of total cellular RNA.

Ribosomal RNA (rRNA) is the most abundant intracellular RNA, making up 80 percent of total RNA. The eukaryotic ribonucleoprotein particle (ribosome) is composed of many proteins and four rRNA molecules (which are classified according to size). Ribosomes reside in the cytoplasm and are the "molecular platform" (the actual physical site of) for protein synthesis.

Transfer RNA (tRNA) molecules contain between seventy-four and ninety-five nucleotides and all tRNAs have similar overall structures. There are twenty individual tRNAs; each one binds to a specific amino acid in the cytoplasm and brings its "activated amino acid" to a ribosome—part of the translational machinery that carries out protein synthesis. Transfer RNA makes up the remaining 15 percent of cellular RNA.

All nucleic acids are polynucleotides, with each nucleotide being made up of a base, a sugar unit, and a phosphate. The composition of DNA differs from that of RNA in two major ways (see Figure 1). Whereas DNA contains the bases guanine (G), cytosine (C), adenine (A), and thymine (T), RNA contains G, C, and A, but it contains uracil (U) in place of thymine. Both DNA and RNA contain a five-membered cyclic sugar (a pentose). RNA contains a ribose sugar. The sugar in DNA, however, is 2′-deoxyribose.

In DNA, each base is linked by a β -glycosidic bond to the C1′ position of the 2′-deoxyribose, and each phosphate is linked to either the C3′ or C5′ position. The linkages are essentially the same in RNA.

DNA is a right-handed, double-stranded helix, in which the bases essentially occupy the interior of the helix, whereas the phosphodiester backbone (sugar-phosphate backbone) more or less comprises the exterior. The bases on the individual strands form intermolecular hydrogen bonds with each other (the complementary Watson–Crick base pairs). An adenine base on one strand interacts specifically with a thymine base on the other, forming two hydrogen bonds and an A–T base pair; while a G–C base pair contains three hydrogen bonds. These interactions possess a specificity that is pivotal to both DNA replication and transcription (see Figure 2).

DNA structure is also described in terms of primary, secondary, and tertiary structures. The primary structure is simply the sequence of nucleotides. The secondary structure refers to the hydrogen bonding between A–T and G–C base pairs. The tertiary structure refers to the larger twists and turns of the DNA molecule. Other features of DNA are the major and

minor grooves that run along the helix that are the target sites for DNA binding proteins involved in replication and transcription. Although DNA can exist in several alternate structures, the B-form of DNA (see Figure 3) is the biologically relevant form.

As stated previously, DNA is the genetic material in humans and in virtually all organisms, including viruses—with the exception of a few viruses that possess RNA as the genetic material.

In complex multicellular organisms (such as humans), DNA carries within itself the instructions for the synthesis and assembly of virtually all the components of the cell and (therefore) for the structure and function of tissues and organs. Within the approximately 3.2 × 10⁹ base pairs (3.2 Gbps) in human DNA, the Human Genome Project has determined that there are a minimum of about 25,000 individual segments that correspond to individual genes. The genes collectively make up only about 2 to 3 percent of the total DNA, but encode the detailed genetic instructions for the synthesis of proteins. Proteins are the "workhorses" of the cell, and in one way or another are responsible for the functions that permit a cell to communicate with other cells and that define the character of the individual cell. A kidney cell is very different from a heart or eye cell. Although every cell contains the same DNA, different subsets of the 25,000 genes are expressed in the different organs or tissues. The expressed genes determine the type of cell that is produced and a cell's ultimate function in a multicellular organism.

Interestingly, there is only approximately a 0.1 percent difference in DNA among humans. The nucleotide sequences of DNA differs between organisms and is a fundamental difference between individuals and between species. For example, our closest (species) relative, the chimpanzee, has DNA that is 98.5 percent identical to that of humans.

see also Deoxyribonucleic acid; Double Helix; Watson, Francis Dewey.

William M. Scovell

Bibliography

Berg, Jeremy M.; Tymoczko, John L.; and Stryer, Lubert (2002). Biochemistry, 5th edition. New York: W. H. Freeman.

Kimball, John W. (1994). Biology, 6th edition. Dubuque, IA: Wm. C. Brown Publishers. Also available from <http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/>.

Nucleic acid

A nucleic acid is a complex organic compound found in all living organisms. Nucleic acids were discovered in 1869 by the Swiss biochemist Johann Friedrich Miescher (1844–1895). Miescher discovered the presence of an unusual organic compound in the nuclei of cells and gave that compound the name nuclein. The compound was unusual because it contained both nitrogen and phosphorus, in addition to carbon, hydrogen, and oxygen. Nuclein was one of the first organic compounds to have been discovered that contained this combination of elements. Although later research showed that various forms of nuclein occurred in other parts of the cell, the name remained in the modified form by which it is known today: nucleic acid.

Structure of nucleic acids

Nucleic acids are polymers, very large molecules that consist of much smaller units repeated many times over and over again. The small units of which polymers are made are known as monomers. In the case of nucleic acid, the monomers are called nucleotides.

Words to Know

Amino acid: One of about two dozen chemical compounds from which proteins are made.

Cytoplasm: The fluid inside a cell that surrounds the nucleus and other membrane-enclosed compartments.

Double helix: The shape taken by DNA molecules in a nucleus.

Genetic engineering: The manipulation of the genetic content of an organism for the sake of genetic analysis or to produce or improve a product.

Monomer: A small molecule that can be combined with itself many times over to make a large molecule, the polymer.

Nitrogen base: A component of the nucleotides from which nucleic acids are made. It consists of a ring containing carbon, nitrogen, oxygen, and hydrogen.

Nucleotide: The basic unit of a nucleic acid. It consists of a simple sugar, a phosphate group, and a nitrogen-containing base.

Nucleus: A compartment in the cell that is enclosed by a membrane and that contains its genetic information.

Phosphate group: A grouping of one phosphorus atom and four oxygen atoms that occurs in a nucleotide.

Protein: A complex chemical compound that consists of many amino acids attached to each other that are essential to the structure and functioning of all living cells.

Ribosomes: Small structures in cells where proteins are produced.

The exact structures of nucleotides and nucleic acids are extraordinarily complex. All nucleotides consist of three components: a simple sugar, a phosphate group, and a nitrogen base. A simple sugar is an organic molecule containing only carbon, hydrogen, and oxygen. Perhaps the best-known of all simple sugars is glucose, the sugar that occurs in the blood of mammals and that, when digested, provides energy for their movement. A phosphate group is simply a phosphorus atom to which four oxygen atoms are attached. And a nitrogen base is a simple organic compound that contains nitrogen in addition to carbon, oxygen, and hydrogen.

Kinds of nucleic acids

The term nucleic acid refers to a whole class of compounds that includes dozens of different examples. The phosphate (P) group in all nucleic acids is exactly alike. However, two different kinds of sugars are found in nucleic acids. One kind of sugar is called deoxyribose. The other kind is called ribose. The difference between the two compounds is that deoxyribose contains one oxygen less (deoxy means "without oxygen") than does ribose. Nucleic acids that contain the sugar deoxyribose are called deoxyribonucleic acid, or DNA; those that contain ribose are called ribonucleic acid, or RNA.

Nucleic acids also contain five different kinds of nitrogen bases. The names of those bases and the abbreviations used for them are adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U). Deoxyribonucleic acids all contain the first four of these nitrogen bases: A, C, G, and T. Ribonucleic acids all contain the first three (A, C, G) and uracil, but not thymine.

DNA and RNA molecules differ from each other, therefore, with regard to the sugar they contain and with regard to the nitrogen bases they contain. They differ in two other important ways: their physical structure and the role they play in living organisms.

Deoxyribonucleic acids (DNA). A single molecule of DNA consists of two very long strands of nucleotides, similar to the structure of all nucleic acids. The two strands are lined up so that the nitrogen bases extending from the sugar-phosphate backbone face each other. Finally, the two strands are twisted around each other, like a pair of coiled telephone cords wrapped around each other. The twisted molecule is known as a double helix.

The function of DNA. One of the greatest discoveries of modern biology occurred in 1953 when the American biologist James Watson (1928– ) and the English chemist Francis Crick (1916– ) uncovered the role of DNA in living organisms. DNA, Watson and Crick announced, is the "genetic material," the chemical substance in all living cells that passes on genetic characteristics from one generation to the next. How does DNA perform this function?

When a biologist says that genetic characteristics are passed from one generation to the next, one way to understand that statement is to say that offspring know how to produce the same kinds of chemicals they need in their bodies as do their parents. In particular, they know how to produce the most important of all chemicals in living organisms: proteins. Proteins are essential to the function and structure of all living cells.

Watson and Crick said that the way nitrogen bases are lined up in a DNA molecule constitute a kind of "code." The code is not all that different from codes you may use with your friends: A = 1, B = 2, C = 3, and so on. In DNA, however, it takes three nitrogen bases to form a code. For example, the combination CGA means one thing to a cell, the combination GTC another, the combination CCC a third, and so on.

Each possible combination of three nitrogen bases in a DNA molecule stands for one amino acid. Amino acids are the chemical compounds from which proteins are formed. For example, the protein that tells a body to make blue eyes might consist of a thousand amino acids arranged in the sequence A₁₅-A₄-A₁₁-A₈-A₅- and so on. What Watson and Crick said was that every different sequence of nitrogen bases in a DNA molecule stands for a specific sequence of amino acid molecules and, thus, for a specific protein. In the example above, the sequence N₄-N₁-N₂-N₃-N₄-N₃-N₃-N₁-N₄ might conceivably stand for the amino acid sequence A₁₅-A₄-A₁₁-A₈-A₅- which, in turn, might stand for the protein for blue eyes.

When any cell sets about the task of making specific chemicals for which it is responsible, then, it "looks" at the DNA molecules in its nucleus. The code contained in those molecules tells the cell which chemicals to make and how to go about making them.

Ribonucleic acid. So what role do ribonucleic acid (RNA) molecules play in cells? Actually that question is a bit complicated because there are at least three important kinds of RNA: messenger RNA (mRNA); transfer RNA (tRNA); and ribosomal RNA (rRNA). In this discussion, we focus on only the first two kinds of RNA: mRNA and tRNA.

DNA is typically found only in the nuclei of cells. But proteins are not made there. They are made outside the cell in small particles called ribosomes. The primary role of mRNA and tRNA is to read the genetic message stored in DNA molecules in the nucleus, carry that message out of the nucleus and to the ribosomes in the cytoplasm of the cell, and then use that message to make proteins.

The first step in the process takes place in the nucleus of a cell. A DNA molecule in the nucleus is used to create a brand new mRNA molecule that looks almost identical to the DNA molecule. The main difference is that the mRNA molecule is a single long strand, like a long piece of spaghetti. The nitrogen bases on this long strand are a mirror image of the nitrogen bases in the DNA. Thus, they carry exactly the same genetic message as that stored in the DNA molecule.

Once formed, the mRNA molecule passes out of the nucleus and into the cytoplasm, where it attaches itself to a ribosome. The mRNA now simply waits for protein production to begin.

In order for that step to take place, amino acid molecules located throughout the cytoplasm have to be "rounded up" and delivered to the ribosome. There they have to be assembled in exactly the correct order, as determined by the genetic message in the mRNA molecule.

The "carriers" for the amino acid molecules are molecules of transfer RNA (tRNA). Each different tRNA molecule has two distinct ends. One end is designed to seek out and attach itself to some specific amino acid. The other end is designed to seek out and attach itself to some specific sequence of nitrogen bases. Thus, each tRNA molecule circulating in the cell finds the specific amino acid for which it is designed. It attaches itself to that molecule and then transfers the molecule to a ribosome. At the ribosome, the opposite end of the tRNA molecule attaches itself to the mRNA molecule in just the right position. This process is repeated over and over again until every position on the mRNA

molecule holds some specific tRNA molecule. When all tRNA molecules are in place, the amino acids positioned next to each other at the opposite ends of the tRNA molecules join with each other, and a new protein is formed.

Applications

Our understanding of the way in which nucleic acids are constructed and they jobs they do in cells has had profound effects. Today, we can describe very accurately the process by which plant and animal cells learn how to make all the compounds they need to survive, grow, and reproduce. Life, whether it be the life of a plant, a lower animal, or a human, can be expressed in very specific chemical terms.

This understanding has also made possible techniques for altering the way genetic traits are passed from one generation to the next. The process known as genetic engineering, for example, involves making conscious changes in the base sequence in a DNA molecule so that a new set of directions is created and, hence, a new variety of chemicals can be produced by cells.

[See also Chromosome; Enzyme; Genetic engineering; Genetics; Mutation ]

Nucleic Acids

Nucleic acids are a group of organic compounds that carry genetic information. Nucleic acids are essential to life since they contain not only a cell's genetic information, but also instructions for carrying out cellular processes. Deoxyribonucleic acid (DNA) is the particular type of nucleic acid out of which genes are made, and genes are the bearers of hereditary traits from parents to offspring.

Nucleic acid was discovered in 1869 by the Swiss biochemist Johann Friedrich Miescher (1844–1895), who first found a sticky, clear chemical in the nucleus of cells. He named it nuclein, and although it later became known as nucleic acid, no one had any idea that it was in some way connected to heredity. The name nucleic acid itself indicates that these clear molecules were first found in the cell nucleus and that they have a mildly acidic character. By 1929, scientists had discovered that there were two types of nucleic acids. One of these contained the sugar ribose (and became known as ribonucleic acid or RNA) and the other contained the sugar deoxyribose (and was called deoxyribonucleic acid or DNA). By the 1930s, most geneticists agreed that the gene was crucial to heredity and was made of some sort of complex chemical, but no one thought it was made of nucleic acid because the acid did not seem to have a complicated enough structure to carry genetic information.

By 1950, however, nucleic acid had been established as the key factor in inheritance, yet in the fall of that year when the young American biochemist James Dewey Watson (1928– ), traveled to Europe to study the chemistry of nucleic acids, no one knew how this chain of fairly simple molecules could contain all the information necessary to form a complex organism. In 1951 when Watson met the English biochemist Francis Harry Compton Crick (1916– ) at the Cavendish Laboratory at Cambridge, England, the two began a collaboration with the goal of determining the structure of DNA (which they believed would then explain how DNA actually works).

In March 1953, the team of Watson and Crick announced that they had discovered the "double helix structure" of the DNA molecule and offered to science what was essentially an explanation of the chemical basis of life itself. Their theory was that the nucleic acid DNA was made up of two twisted strands that are held together by base pairs that make up the actual coded instructions. Each DNA base is, therefore, like a letter in the alphabet, and a sequence of bases can be thought of as forming a message. Nucleic acids were found not only to contain genetic information (DNA), but were also able to carry that information from genes in the nucleus to other structures in the cell. Thus, the building of proteins was found to be controlled by the group of nucleic acids known as ribonucleic acid (RNA). Geneticists eventually came to describe RNA according to its function in the cell, messenger RNA (mRNA) and transfer RNA (tRNA). Both types of RNA are essential for a DNA molecule to make a copy of itself (which in turn is how proteins are made). mRNA passes out of the nucleus and carries the message for making a protein. tRNA reads this message and transfers the right amino acid to where they form proteins. Watson and Crick's landmark discovery of the nature and function of nucleic acids provided the foundation for understanding the chemical basis of life.

[See alsoChromosome; DNA; Enzyme; Genetic Engineering; Genetics; RNA ]

Nucleic Acid

Two nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are found in living things which serve to store, translate, and pass on the genetic information of an organism to the next generation. Nucleic acids are universal to all life, in eukaryotic and prokaryotic cells, as well as in viruses. The mitochondria of eukaryotic cells also contain some DNA, known as mitochondrial DNA.

Nucleic acids have a special physical structure that lets them be the information chemicals of living things. DNA and RNA are both giant molecules consisting of long chains of small, repeating chemical units called nucleotides joined together like the box cars of a train. Each nucleotide unit carries a single piece of information, corresponding to an individual letter in a word; when nucleotides are strung together in long chains, the nucleic acids contain messages corresponding to words and sentences. The information in the genes (lengths of nucleic acid) in the nucleus is translated by cells into polypeptides and proteins in the cytoplasm. The cell then can read these “words” and know what to do.

Proteins are important because they make up cell structure and because they function as enzymes, which are catalysts which control the various biochemical pathways in cell metabolism.

There are important differences between the two nucleic acids. DNA has two long chains, or strands, of nucleotides that mirror each other and which are arranged in a double helix format. RNA has a single strand. Furthermore, the four bases of the nucleotides of DNA are adenine, cytosine, guanine, and thymine, while those of RNA lack thymine, which is substituted by uracil. The DNA, copies of which are found in every cell of the body, represents the permanent copy of an organism’s entire genetic information, which is passed on to the next generation. The RNA is never more than a temporary copy of a small fraction of the information. There are three types of RNA: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). DNA serves as the master set of blueprints for all of an organism’s functions, and RNA acts as the specialist that interprets a small portion of these instructions for use in the cells and tissues of the organism. In short, living organisms use the nucleic acid DNA to preserve their biological information and the nucleic acid RNA to access it.

See also Chromosome; Gene; Genetics.

Nucleic acid

Two nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) , are found in living things which serve to store, translate, and pass on the genetic information of an organism to the next generation. Nucleic acids are universal to all life, in eukaryotic and prokaryotic cells, as well as in viruses. The mitochondria of eukaryotic cells also contain some DNA, known as mitochondrial DNA.

Nucleic acids have a special physical structure that lets them be the information chemicals of living things. DNA and RNA are both giant molecules consisting of long chains of small, repeating chemical units called nucleotides joined together like the box cars of a train. Each nucleotide unit carries a single piece of information, corresponding to an individual letter in a word; when nucleotides are strung together in long chains, the nucleic acids contain messages corresponding to words and sentences. The information in the genes (lengths of nucleic acid) in the nucleus is translated by cells into polypeptides and proteins in the cytoplasm. The cell then can read these "words" and know what to do.

Proteins are important because they make up cell structure and because they function as enzymes, which are catalysts which control the various biochemical pathways in cell metabolism .

There are important differences between the two nucleic acids. DNA has two long chains, or strands, of nucleotides that mirror each other and which are arranged in a double helix format. RNA has a single strand. Furthermore, the four bases of the nucleotides of DNA are adenine, cytosine, guanine, and thymine, while those of RNA lack thymine, which is substituted by uracil. The DNA, copies of which are found in every cell of the body, represents the permanent copy of an organism's entire genetic information, which is passed on to the next generation. The RNA is never more than a temporary copy of a small fraction of the information. There are three types of RNA: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). DNA serves as the master set of blueprints for all of an organism's functions, and RNA acts as the specialist that interprets a small portion of these instructions for use in the cells and tissues of the organism. In short, living organisms use the nucleic acid DNA to preserve their biological information and the nucleic acid RNA to access it.

See also Chromosome; Gene; Genetics.