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The central dogma of
molecular biology was
first enuciated by
Francis Crick in
1958 and re-stated in a
Nature paper published in
1970. The precise definition
is The central dogma of
molecular biology deals with the
detailed residue-by-residue
transfer of sequential
information. It states that such
information cannot be transferred
from
protein to either protein or
nucleic acid. In other
words, once information gets into
protein it can't flow back to
nucleic acid.
The central dogma is often
misunderstood. It is frequently
confused with the standard pathway
of information flow from "DNA
to
RNA to
protein". There are
notable exceptions to the
normal pathway of information flow
and these are often mistakenly
referred to as exceptions to the
central dogma. There are no known
exceptions to the actual central
dogma correctly stated.
The standard information flow
pathway can be summarized in a
very short and oversimplified
manner as "DNA makes RNA makes
proteins, which in turn facilitate
the previous two steps as well as
the replication of DNA", or simply
"DNA → RNA → protein". This
process is therefore broken down
into three steps:
transcription,
translation, and
replication. By new knowledge
of the RNA processing, a fourth
step must be included:
splicing.
Transcription
Transcription is the process
by which the information contained
in a section of DNA is transferred
to a newly assembled piece of
messenger RNA (mRNA). It is
facilitated by
RNA polymerase and
transcription factors.
Splicing
In
eukaryote cells the primary
transcript (pre-mRNA) is
processed. One or more sequences (introns)
are cut out. The mechanism of
alternative splicing makes it
possible to produce different
mature mRNA molecules, depending
on what sequences are treated as
introns and what remain as
exons. However, not all living
cells have mRNA that undergoes
splicing; splicing is absent in
prokaryotes.
Translation
Eventually, this mature mRNA
finds its way to a
ribosome, where it is
translated. In
prokaryotic cells, which have
no nuclear compartment, the
process of transcription and
translation may be linked
together. In
eukaryotic cells, the site of
transcription (the
nucleus) is usually separated
from the site of translation (the
cytoplasm), so the mRNA must
be transported out of the nucleus
into the cytoplasm, where it can
be bound by ribosomes. The mRNA is
read by the ribosome as triplate
codons, usually beginning with
an AUG, or initiator methonine
codon downstream of the
ribosome binding site.
Complexes of
initiation factors and
elongation factors bring
amino acylated
transfer RNAs (tRNAs) into the
ribosome-mRNA complex, matching
the codon in the mRNA to the anti-codon
in the tRNA, thereby adding the
correct
amino acid in the sequence
encoding the gene. As the amino
acids are linked into the growing
peptide chain, they begin folding
into the correct conformation.
This folding continues until the
nascent polypeptide chains are
released from the ribosome as a
mature protein. In some cases the
new polypepeptide chain requires
additional processing to make a
mature protein. The correct
folding process is quite complex
and may require other proteins,
called
chaperone proteins.
Occasionally proteins themselves
can be further spliced, when this
happens the inside "discarded"
section is known as an
intein.
Replication
Finally, as the final step in
the Central Dogma, to transmit the
genetic information between
parents and progeny, the DNA must
be replicated faithfully.
Replication is carried out by a
complex group of proteins that
unwind the
superhelix, unwind the
double-stranded DNA helix,
and, using
DNA polymerase and its
associated proteins, copy or
replicate the master template
itself so the cycle can repeat DNA
→ RNA → protein in a new
generation of cells or organisms.
Exceptions to the central
dogma
The central dogma is not really
a
dogma in the traditional sense
of the word - like all
scientific theories it is
modified as we learn more details
of the processes.
The biggest revolution in the
central dogma was the discovery of
retroviruses, which transcribe
RNA into DNA through the use of a
special enzyme called
reverse transcriptase has
resulted in an exception to the
central dogma; RNA → DNA → RNA →
protein. Also, some virus species
are so primitive that they use
only RNA → proteins, having not
developed DNA. With the discovery
of
prions, a new exception to the
central dogma has been discovered,
Protein → Protein. That is,
proteins directly replicating
themselves by making
conformational changes in other
proteins. Although retroviruses,
certain primitive viruses, and
prions may violate the central
dogma, they are technically not
considered "alive", and thus the
rule that "all cellular life
follows the central dogma" still
holds true.
Criticisms of the central
dogma
Some researchers in the area of
systems biology claim that
scientists sometimes misuse the
central dogma as a research
strategy. They claim that an
uncritical reading of the central
dogma could inhibit novel
approaches to understanding
multicellular development of
organisms as well as multicellular
diseases. The central dogma is
often used as a reductionist
research strategy that proceeds
bottom up attempting to explain
all biological phenomena in
molecular terms. Although they
don't dispute the very specific
reading of the central dogma,
these researchers claim that a
reductionist research strategy may
limit the understanding of complex
systems that cannot be analyzed by
their molecular interactions alone
because of the combinatorial
complexity involved (Werner 2005).
See also
References
