Central Dogma of Molecular Biology

Academic Script

1. Introduction
It has been well established that „‟DNA is the molecule of life‟‟. Everything we
are, we do or can do is because of a complex system of molecules that govern
the biochemical changes taking place in each cell of our body. We have learnt
that we are made up of cells. Our cells are made up of molecules of
carbohydrates, proteins, vitamins, minerals, fats and nucleic acids. Of these
molecules, it is the DNA that carries all the information necessary to synthesize
proteins. Proteins in turn govern the synthesis and functioning of the other
molecules. Hence, DNA holds a prime position as the molecule that has the
necessary information to generate, control and coordinate all life processes
within a cell.

The concept of identifying DNA as the molecule having the information for life
began with the early ideas of Sir Archibald Garrod in 1905. Garrod had
identified the link between an inheritable disease, Alkaptonuria and its metabolic
defect. He explained that these diseases were related to metabolic blocks, due
to a defective protein (enzyme). He reasoned that if patients had inherited a
single metabolic defect, the specific „units‟ of inheritance (genes) which control
the synthesis of enzymes, may be faulty and thus cause the block.

Thirty-three years later, George Beadle and Edward Tatum designed an

experiment to prove that in N. crassa the fungal enzyme catalyzing a reaction in
a defective pathway, may be non-functional due to a gene mutation. They
carried out chemical analysis of cultured cell extracts and demonstrated a
different defective enzyme in each mutant strain. They thus proposed the “One
gene – one enzyme‟‟ hypothesis. This hypothesis emphasizes that each
inherited gene mutation may correspond to a defective enzyme. This was
another milestone in the world of Genetics, confirming that the gene or DNA
was responsible for providing the correct information to direct the synthesis of a
protein such as an enzyme, which regulated life processes.

Biochemists Linus Pauling and Harvey Itano carried out experiments to prove
that the genetic difference between alpha and beta chains of Hemoglobin
suggest that two genes give the code/information for Hemoglobin. One gene
codes for one polypeptide, which resulted in the emergence of a more precise
hypothesis. Polypeptide chains, which have defined sequences of amino acids,
are encoded by genes. Therefore the information on DNA directs the synthesis
of amino acids to form a polypeptide. Pioneering research carried out by
Nirenberg and Khorana helped to identify that specific enzymes (i.e. RNA
polymerases) „read‟ the sequence of nucleotides three at a time, as triplet
codons. These codons were then copied to form a complementary code on an
RNA molecule. With the help of another RNA, the transfer RNA, the code was
translated into a corresponding sequence of amino acids.
The RNA molecule which is said to „copy‟ the information from DNA in triplet
codons is actually a large molecule which is synthesized by coping each code
on the DNA, base for matching complementary base. This nascent RNA is
termed as “heterogeneous nuclear RNA” because it has copied or
TRANSCRIBED both coding and non-coding sequences from the DNA. The
process is termed TRANSCRIPTION. The large molecule (hnRNA) is too large
to pass through the nucleopores from nucleus to cytoplasm, for the purpose of
being translated into amino acid sequences. Hence, the non-coding sequences,
which are not translated, are then cut or „spliced‟ and only those sequences
actually coding for amino acids are joined together. The result is a much smaller
molecule termed as “the messenger RNA” since it carries only the required
sequences or precise message to synthesize a protein. This m-RNA can now
pass from nucleus to cytoplasm for being converted into amino acid sequences.

Molecular Biologists agree therefore, that the basic information for life flows
from DNA to RNA to PROTEIN. This simple maxim has provided the answers to
many questions in Molecular Biology, Genetics and Biochemistry. It has also
yielded the solution to many problems in these areas of the life sciences but
above all, this basic principle has given a firm foundation to understanding and
explaining fundamental processes in life and hence it is often termed as the
“Central Dogma of Molecular Biology‟‟ or „the Central Dogma of Life‟ which
states that “DNA makes RNA makes Protein”.

The Central Dogma refers to the basic principle or the Foundation on which the
entire study of Molecular Biology rests. The central dogma of molecular
biology explains the flow of genetic information within a biological system,
which controls all life processes.

To illustrate this concept diagrammatically: This has been described in simple

terms as "DNA makes RNA makes protein."
This concept was first formulated by Francis Crick in 1958 and published in a
research paper in Nature in 1970. While Francis Crick and George Gamov
originally proposed the „Central Dogma of Molecular Biology” clearly stating that
protein synthesis proceeds due to the information transfer from DNA to RNA to
protein, Molecular biologists focused all efforts to investigate the hypothesis,
confirm it or refute it. It finally led to a period of research in molecular biology
where researchers began to re-define molecular-level understandings of protein
synthesis. Today, this research centers around explaining the causes of various
diseases and disorders in terms of the altered or truncated expression of
information on the DNA and its subsequent impact on the protein structure and
function. This has culminated in the Era of Epigenetics.

The central dogma therefore emphasizes that the genetic code on the DNA
directs the code on the RNA which in turn, regulates the synthesis of Protein.
To elucidate this statement we must remember that the biological information is
contained in the DNA molecule in the form of triplet bases mentioned in the
Genetic Code. This triplet sequence is copied base for base exactly when the
DNA is transcribed into a complementary sequence of RNA- the heterogeneous
nuclear RNA (hnRNA). The non-coding sequences are then spliced out of this
molecule to synthesize a messenger RNA containing the exact formation for
specific sequence of amino acids to be joined in the process of Translation of
Protein Synthesis.

Thus everything we are or do as living beings has been attributed to the

proteins that make up the living system. But every protein is synthesized under
directions from the code contained in the DNA, through an RNA molecule.
Hence the Central Dogma stresses that Genetic Information flows from the DNA
to the RNA to the Proteins.
Dr. Francis Crick had documented in his autobiography that the he used the
term “Dogma” only to emphasize the significance of the concept. He wanted to
use terms like “Hypothesis”, “Assumption” but they sounded too indefinite. Dr.
Crick wanted a powerful word to emphasize that this was the basic theory and
so he chose Dogma. In evolutionary or molecular biological theory, Crick's
proposal had no connection with the actual meaning of the word "dogma".

The dogma referred to here is therefore a framework for understanding the

transfer of sequence information between sequential information-carrying
biopolymers (DNA and RNA) to produce the related sequence units in shorter
polymers (protein).

It has been speculated that 80% of the human genome is transcribed, even
though only 1% codes for proteins, although it is likely that transcription of most
genes do not result in the synthesis of a functional protein.

2. Biological sequence information

The biopolymers that comprise DNA, RNA and amino acids are linear polymers
(i.e.: each monomer is connected to at most two other monomers). The
sequence of their monomers effectively encodes information. The transfer of
information described by the central dogma is authentic, deterministic transfers,
wherein one biopolymer's sequence is used as a template for the construction
of another biopolymer with a sequence that is entirely dependent on the original
biopolymer's sequence.

According to the central dogma, these information transfers are then grouped
into 3 sets of 3:

3 general transfers (occurs normally in most cells),

3 special transfers (known to occur, but only under specific conditions in case
of some viruses or under laboratory conditions.),
3 unknown transfers (not much is known regarding such transfer.)

The general transfers include DNA to DNA, DNA to RNA and RNA to protein.
The special transfers include transfer of information from RNA to DNA and RNA
to RNA.

Reverse transcription is the transfer of information from RNA to DNA (the

reverse of normal transcription). This is known to occur in the case of
retroviruses, such as HIV, as well as in eukaryotes, in the case of retro
transposons and telomere synthesis. It is the process by which the genetic
information from RNA will be assembled into new DNA.

Thus, this basic concept that genetic information is transferred from the DNA
molecule to a complementary RNA which leads to the synthesis of Protein is the
foundation of studies related to the control of gene expression or
EPIGENETICS. Today Scientists are looking for answers to most diseases and
disorders through epigenetic research, which is based on the Central Dogma of
Molecular Biology: DNA makes RNA makes Protein.