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Molecular biology is the story of the molecules of life, their relationships, and
how these interactions are controlled. The term has more than one definition.
Some define it very broadly as the attempt to understand biological
phenomena in molecular terms. But this definition makes molecular biology
difficult to distinguish from another well-known discipline, biochemistry.
Another definition is more restrictive and therefore more useful: the study of
gene structure and function at the molecular level that make up the cell. This
attempt to explain genes and their activities in molecular terms. Molecular
biology grew out of the disciplines of genetics and biochemistry. In other words,
that biological information is carried by the nucleic acids, DNA and RNA—has
transformed biology.
The most famous molecules in cells are DNA, RNA and Proteins, and much
of molecular biology focuses on these molecules — reading DNA, working with
DNA, translating RNA, making proteins and understanding how cells use DNA
and RNA.
While molecular biology was established as an official branch of science in
the 1930s, the term wasn't coined until 1938 by Warren Weaver. Molecular
biology arose as an attempt to answer the questions regarding the mechanisms of
genetic inheritance and the structure of a gene.
Warren Weaver
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In 1953, James Watson and Francis Crick published the double helical
structure of DNA courtesy of the X-ray crystallography work done by Rosalind
Franklin and Maurice Wilkins. Watson and Crick described the structure of
DNA and the interactions within the molecule.
Thus, Molecular Biology as a field, however, was originally born from the
development of tools and methods that allow the direct manipulation of DNA
both in vitro and in vivo in numerous organisms.
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HISTORY OF DNA AS THE GENETIC MATERIAL
(BASIC MOLECULAR BIOLOGY)
On April 25, 1953, in the British Journal Nature, a published paper, two
columns in length, appeared. It was entitled "Molecular Structure of Nucleic
Acids: A Structure for Deoxyribose Nucleic Acid" and was authored by the
American and the Englishman . The
structure they proposed has, they say in the first paragraph, "novel features
which are of considerable biological interest."
This paper was the culmination of work that stretched back 85 years to
, the German scientist who had accidentally
discovered DNA (deoxyribonucleic acid) in 1869. He called it nuclein because it
was isolated from nuclei of pus cells and salmon sperm. Miescher reported his
findings in 1871
was interested in studying proteins, as these seemed to be the
obvious molecules of life carrying out the functions of a cell. He was isolating
proteins from white blood cells washed from pus-soaked (discarded surgical)
bandages (wound) when he came across a substance that, unlike protein, was
resistant to cleavage by protein-digesting enzymes—the proteases—and was also
surprisingly high in the chemical phosphate, and he separated the substance into
a basic part (which is now known as DNA) and an acidic part (a class of acidic
proteins that bind to basic DNA). Miescher in fact thought it was a phosphate
storage molecule and he had no idea of its significance. Since it was obviously
not protein and it had been found in the cell nucleus, he called it nuclein.
Watson & Crick
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In the early 1900s two types of ‘nuclein’, now called DNA and RNA
(ribonucleic acid), were isolated, but at first the differences between them were
not apparent. They were named according to their source material, with RNA
termed ‘Yeast nuclein’ and DNA as ‘Pancreas nucleic acid’.
In 1866, had published his work that led to the principles of
independent segregation and assortment of genes. The late 1800s are
considered the time of the birth of genetics. And at its birth, the new science was
already started in two directions. Mendel's work would lay the foundation of
what has been called classical genetics, and Miescher's had begun what is now
called molecular genetics. The two scientists apparently worked without
knowledge of the other's discoveries.
The classical geneticists have focused on how genes are transferred from one
generation to the next (inheritance), gene location within chromosomes,
chromosomal rearrangements, and the concept of dominance. The molecular
geneticists, on the other hand, have focused on the structure of genes and on how
genes work and are regulated.
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An initial step in identifying DNA as the source of genetic information came
with the discovery of a phenomenon called transformation. This phenomenon
was first observed in 1928 by Fred Griffith, an English physician whose special
interest was the bacterium that causes pneumonia: Streptococcus pneumoniae.
At the turn of the century, Albrecht Kossel had demonstrated that a nucleic
acid was composed of a (adenine, guanine, cytosine, thymine,
or ) a , and a .
Then, by the early 1930s, largely as the result of the work of P. A. T. Levene
(Phoebus Aaron Theodore Levene), the arrangement of the bases, sugar, and
phosphate was discovered. A single base is linked to the sugar, which in turn is
linked to the phosphate. The resulting structure is , the fundamental
unit of nucleic acids. Levene, along with other workers, also discovered that the
sugar of nuclein is . And he discovered that there are in fact two
nucleic acids: , or RNA (actually discovered by Kossel), and
, or DNA (Miescher's nuclein).
Albrecht Kossel
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The discovery of the components of nucleic acids, in particular DNA, then led
to the first models of the structure of DNA. Takahashi, in 1930, proposed the
"tetranucleotide" structure for DNA. In this model, the nucleotides of adenine,
guanine, cytosine, and thymine repeat in a regular pattern. Thus, the idea that
DNA is composed of simple parts arranged in a simple way was born.
At the forefront of the biological molecules studied were the three major
polymers of life: DNA, RNA, and protein. But how was the genetic information
transferred between them? The answer had to wait until the 1960s.
The next key step towards the solution came in the 1940s, from the work by
Oswald Avery, Colin MacLeod, and Maclyn McCarty of the Rockefeller
Institute, New York. They showed that it was DNA and not protein that could
transfer virulence in bacteria and this led them to propose DNA as the heritable
molecule. Some were hesitant to let go of the idea that only proteins had the
complexity to carry the code.
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In 1952, Alfred Hershey and Martha Chase, working on viruses that infect
bacteria called bacteriophages, showed that it was only the DNA from the virus
that entered the bacterium and coded for new viral progeny. They concluded that
the code was in the . After all, DNA resides in the cell nucleus,
and the nucleus was the major contribution from the male sperm to a fertilized egg.
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The line of research led to the discovery that DNA is the hereditary material.