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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.