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I INTRODUCTION  Deoxyribonucleic Acid (DNA), genetic material of all
cellular organisms and most viruses. DNA carries the information needed
to direct protein synthesis and replication. Protein synthesis is the
production of the proteins needed by the cell or virus for its
activities and development. Replication is the process by which DNA
copies itself for each descendant cell or virus, passing on the
information needed for protein synthesis. In most cellular organisms,
DNA is organized on chromosomes located in the nucleus of the cell.
II STRUCTURE ÂÂ
A molecule of DNA consists of two chains, strands composed of a large
number of chemical compounds, called nucleotides, linked together to
form a chain. These chains are arranged like a ladder that has been
twisted into the shape of a winding staircase, called a double helix.
Each nucleotide consists of three units: a sugar molecule called
deoxyribose, a phosphate group, and one of four different
nitrogen-containing compounds called bases. The four bases are adenine
(A), guanine (G), thymine (T), and cytosine (C). The deoxyribose
molecule occupies the center position in the nucleotide, flanked by a
phosphate group on one side and a base on the other. The phosphate group
of each nucleotide is also linked to the deoxyribose of the adjacent
nucleotide in the chain. These linked deoxyribose-phosphate subunits
form the parallel side rails of the ladder. The bases face inward toward
each other, forming the rungs of the ladder.
The nucleotides in one DNA strand have a specific association with the
corresponding nucleotides in the other DNA strand. Because of the
chemical affinity of the bases, nucleotides containing adenine are
always paired with nucleotides containing thymine, and nucleotides
containing cytosine are always paired with nucleotides containing
guanine. The complementary bases are joined to each other by weak
chemical bonds called hydrogen bonds.
In 1953 American biochemist James D. Watson and British biophysicist
Francis Crick published the first description of the structure of DNA.
Their model proved to be so important for the understanding of protein
synthesis, DNA replication, and mutation that they were awarded the 1962
Nobel Prize for physiology or medicine for their work.
III PROTEIN SYNTHESIS ÂÂ
DNA carries the instructions for the production of proteins. A protein
is composed of smaller molecules called amino acids, and the structure
and function of the protein is determined by the sequence of its amino
acids. The sequence of amino acids, in turn, is determined by the
sequence of nucleotide bases in the DNA. A sequence of three nucleotide
bases, called a triplet, is the genetic code word, or codon, that
specifies a particular amino acid. For instance, the triplet GAC
(guanine, adenine, and cytosine) is the codon for the amino acid
leucine, and the triplet CAG (cytosine, adenine, and guanine) is the
codon for the amino acid valine. A protein consisting of 100 amino acids
is thus encoded by a DNA segment consisting of 300 nucleotides. Of the
two polynucleotide chains that form a DNA molecule, only one strand,
called the sense strand, contains the information needed for the
production of a given amino acid sequence. The other strand aids in
replication.
Protein synthesis begins with the separation of a DNA molecule into two
strands. In a process called transcription, a section of the sense
strand acts as a template, or pattern, to produce a new strand called
messenger RNA (mRNA). The mRNA leaves the cell nucleus and attaches to
the ribosomes, specialized cellular structures that are the sites of
protein synthesis. Amino acids are carried to the ribosomes by another
type of RNA, called transfer RNA (tRNA). In a process called
translation, the amino acids are linked together in a particular
sequence, dictated by the mRNA, to form a protein.
A gene is a sequence of DNA nucleotides that specify the order of amino
acids in a protein via an intermediary mRNA molecule. Substituting one
DNA nucleotide with another containing a different base causes all
descendant cells or viruses to have the altered nucleotide base
sequence. As a result of the substitution, the sequence of amino acids
in the resulting protein may also be changed. Such a change in a DNA
molecule is called a mutation. Most mutations are the result of errors
in the replication process. Exposure of a cell or virus to radiation or
to certain chemicals increases the likelihood of mutations.
IV REPLICATION ÂÂ
In most cellular organisms, replication of a DNA molecule takes place in
the cell nucleus and occurs just before the cell divides. Replication
begins with the separation of the two polynucleotide chains, each of
which then acts as a template for the assembly of a new complementary
chain. As the old chains separate, each nucleotide in the two chains
attracts a complementary nucleotide that has been formed earlier by the
cell. The nucleotides are joined to one another by hydrogen bonds to
form the rungs of a new DNA molecule. As the complementary nucleotides
are fitted into place, an enzyme called DNA polymerase links them
together by bonding the phosphate group of one nucleotide to the sugar
molecule of the adjacent nucleotide, forming the side rail of the new
DNA molecule. This process continues until a new polynucleotide chain
has been formed alongside the old one, forming a new double-helix
molecule.
V TOOLS AND PROCEDURES ÂÂ
Several tools and procedures facilitate are used by scientists for the
study and manipulation of DNA. Specialized enzymes, called restriction
enzymes, found in bacteria act like molecular scissors to cut the
phosphate backbones of DNA molecules at specific base sequences. Strands
of DNA that have been cut with restriction enzymes are left with
single-stranded tails that are called sticky ends, because they can
easily realign with tails from certain other DNA fragments. Scientists
take advantage of restriction enzymes and the sticky ends generated by
these enzymes to carry out recombinant DNA technology, or genetic
engineering. This technology involves removing a specific gene from one
organism and inserting the gene into another organism.
Another tool for working with DNA is a procedure called polymerase chain
reaction (PCR). This procedure uses the enzyme DNA polymerase to make
copies of DNA strands in a process that mimics the way in which DNA
replicates naturally within cells. Scientists use PCR to obtain vast
numbers of copies of a given segment of DNA.
DNA fingerprinting, also called DNA typing, makes it possible to compare
samples of DNA from various sources in a manner that is analogous to the
comparison of fingerprints. In this procedure, scientists use
restriction enzymes to cleave a sample of DNA into an assortment of
fragments. Solutions containing these fragments are placed at the
surface of a gel to which an electric current is applied. The electric
current causes the DNA fragments to move through the gel. Because
smaller fragments move more quickly than larger ones, this process,
called electrophoresis, separates the fragments according to their size.
The fragments are then marked with probes and exposed on X-ray film,
where they form the DNA fingerprintâ€â€a pattern of characteristic black
bars that is unique for each type of DNA.
A procedure called DNA sequencing makes it possible to determine the
precise order, or sequence, of nucleotide bases within a fragment of
DNA. Most versions of DNA sequencing use a technique called primer
extension, developed by British molecular biologist Frederick Sanger. In
primer extension, specific pieces of DNA are replicated and modified, so
that each DNA segment ends in a fluorescent form of one of the four
nucleotide bases. Modern DNA sequencers, pioneered by American molecular
biologist Leroy Hood, incorporate both lasers and computers. Scientists
have completely sequenced the genetic material of several
microorganisms, including the bacterium Escherichia coli. In 1998,
scientists achieved the milestone of sequencing the complete genome of a
multicellular organismâ€â€a roundworm identified as Caenorhabditis
elegans. The Human Genome Project, an international research
collaboration, has been established to determine the sequence of all of
the three billion nucleotide base pairs that make up the human genetic
material.
An instrument called an atomic force microscope enables scientists to
manipulate the three-dimensional structure of DNA molecules. This
microscope involves laser beams that act like tweezersâ€â€attaching to
the ends of a DNA molecule and pulling on them. By manipulating these
laser beams, scientists can stretch, or uncoil, fragments of DNA. This
work is helping reveal how DNA changes its three-dimensional shape as it
interacts with enzymes.
VI APPLICATIONS  Research into DNA has had a significant impact on
medicine. Through recombinant DNA technology, scientists can modify
microorganisms so that they become so-called factories that produce
large quantities of medically useful drugs. This technology is used to
produce insulin, which is a drug used by diabetics, and interferon,
which is used by some cancer patients. Studies of human DNA are
revealing genes that are associated with specific diseases, such as
cystic fibrosis and breast cancer. This information is helping
physicians to diagnose various diseases, and it may lead to new
treatments. For example, physicians are using a technology called
chimeriplasty, which involves a synthetic molecule containing both DNA
and RNA strands, in an effort to develop a treatment for a form of
hemophilia.
Forensic science uses techniques developed in DNA research to identify
individuals who have committed crimes. DNA from semen, skin, or blood
taken from the crime scene can be compared with the DNA of a suspect,
and the results can be used in court as evidence.
DNA has helped taxonomists determine evolutionary relationships among
animals, plants, and other life forms. Closely related species have more
similar DNA than do species that are distantly related. One surprising
finding to emerge from DNA studies is that vultures of the Americas are
more closely related to storks than to the vultures of Europe, Asia, or
Africa (see Classification).
Techniques of DNA manipulation are used in farming, in the form of
genetic engineering and biotechnology. Strains of crop plants to which
genes have been transferred may produce higher yields and may be more
resistant to insects. Cattle have been similarly treated to increase
milk and beef production, as have hogs, to yield more meat with less
fat.
VII SOCIAL ISSUES  Despite the many benefits offered by DNA
technology, some critics argue that its development should be monitored
closely. One fear raised by such critics is that DNA fingerprinting
could provide a means for employers to discriminate against members of
various ethnic groups. Critics also fear that studies of people’s DNA
could permit insurance companies to deny health insurance to those
people at risk for developing certain diseases. The potential use of DNA
technology to alter the genes of embryos is a particularly controversial
issue.
The use of DNA technology in agriculture has also sparked controversy.
Some people question the safety, desirability, and ecological impact of
genetically altered crop plants. In addition, animal rights groups have
protested against the genetic engineering of farm animals.
Despite these and other areas of disagreement, many people agree that
DNA technology offers a mixture of benefits and potential hazards. Many
experts also agree that an informed public can help assure that DNA
technology is used wisely.
"Deoxyribonucleic Acid," Microsoft® Encarta® Encyclopedia 2000. ©
1993-1999 Microsoft Corporation. All rights reserved.
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