Crick’s Central Dogma of Molecular Biology – DNA to RNA to Protein
The idea that each organism possesses a unique genetic code which is passed to future generations was hypothesised long before the actual mechanisms, or indeed the source, of such inheritable information was agreed. After Mendel (1857) demonstrated that phenotypic characteristics could be transferred from parent to offspring, Fred Griffith set out in 1928 to find evidence that the molecule responsible for preserving and transmitting this information was DNA. This was later confirmed conclusively by experiments conducted by Avery and (later) by Hershey & Chase, establishing that DNA was indeed the arsenal of heritable information. From this affirmation and the knowledge that RNA was the immediate precursor for protein, Francis Crick proposed in a 1954 paper – and reasserted in 1970 – formulated a flow diagram which has become known as the central dogma of molecular biology: DNA to RNA to Protein.
The central dogma is essentially a framework that outlines the transfer of sequential information from storage as DNA to the expression of that information as a functional entity as protein. Most importantly, it dictates that information can only flow from nucleic acid to protein, and not from protein to nucleic acid i.e. that “once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958). At the time of print, all evidence suggested that this transfer or flow of information occurred linearly, however modern advances in molecular biology and genetics have shown that this idea was too simple.
The interrelationship between these three important molecules may be more complex than once thought, however the essential concept still holds true. All organisms (with the exception of some viruses, which use RNA) use DNA as a storage facility for their genetic information. This information, which in reality is triplet base pair codons, is then used a template to be faithfully transcribed to an intermediate RNA. Once transcription is complete, it can then be translated in the ribosome to a corresponding amino acid sequence that codes for the assembly of a functional protein. The dogma infers that it is DNA that directs the development of the organism and that protein formation ultimately relies on the DNA sequence. Additionally, the concept is also important in that it stresses that the information contained within DNA must first depend on RNA for transport. Significantly, it focuses on protein as the product of gene expression, an idea that is now well understood due to successful mapping of the genome.
Modern discoveries have highlighted that the flow of genetic information is much more dynamic. For example, some RNA does not code for protein and instead is destined to remain as an RNA nucleotide. This type of RNA is known as functional or ncRNA – i.e. non-coding – such as tRNA and rRNA. Additionally, ribozymes can act as catalysts, performing their own ‘protein’ functions without ever completed the sequential route all the way to protein. Another modern extension of the dogma is that RNA can also act as a template for DNA synthesis. This process is known as reverse transcription which uses the enzyme reverse transcriptase and has been demonstrated to exist in retroviruses. These findings are important for the development of the theory as it confirms Crick’s postulations that RNA could go back to DNA and further extends our understanding of the central concept.
The importance of the central dogma as a concept is perhaps best illustrated, somewhat paradoxically, by the one discovery which directly challenges it. In his original assertions, Crick explicitly stated that ‘transfer from protein to protein’ was impossible. It is now widely accepted that infectious proteins known as prions, previously thought to be viral in nature, are built directly from protein by triggering abnormal synthesis from its native form. This initially sparked a myriad of papers postulating counter theories, based on the assumption that protein self replication violated the central dogma. It is clear from such actions that the central dogma has core significance that has developed way beyond the actual statements in Crick’s original paper. Scientific discovery in every field is fueled by the desire to find simple, underlying theories that can explain the many complexities of their endeavors in an uncomplicated theoretical framework. We know that DNA is the root of our heritable information and we know that the functional units that make life possible are proteins. Despite requiring some adjustment to the finer detail Crick’s version of the central dogma certainly laid such a foundation, giving biologists a central concept to both orientate from and build around.