DNA
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
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 (abbreviated 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.
IV REPLICATION
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 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. 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. It is useful for this purpose, because 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.
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 and 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.
