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. b4b16bv
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
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.
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
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 fingerprint—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 organism—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 tweezers—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
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.