Central dogma of molecular biology
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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.
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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
- 2005 Werner, E., Genome Semantics, In Silico Multicellular Systems and the Central Dogma (http://www.febsletters.org/article/PIIS0014579305001845/abstract), FEBS Letters 579, pp 1779-1782 (March 21, 2005).de:Ein-Gen-ein-Enzym-Hypothese
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