Central Dogma of Molecular Biology
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The central dogma of molecular biology describes the flow of genetic information within biological systems. It was first formulated by Francis Crick in 1958 and later clarified in 1970. The dogma states that information flows from DNA to RNA to protein and that information cannot flow back from protein to nucleic acid.
Central dogma provides a framework for understanding the transfers of sequential information between biopolymers in cells. The main classes of biopolymers involved are DNA, RNA, and proteins. There are 3 types of transfers: general transfers that normally occur in cells, special transfers only seen under certain conditions, and unknown transfers thought never to occur naturally.
The general transfers describe the normal flow of biological information in cells:
1. DNA replication: DNA is copied to DNA during cell division so each new cell has a complete copy of the genome. This involves enzymes like helicase, polymerase, ligase.
2. Transcription: DNA information is copied into messenger RNA (mRNA). This involves RNA polymerase and transcription factors. The mRNA contains codes for making a specific protein.
3. Translation: The mRNA provides the information to synthesize proteins. This occurs on ribosomes and involves transfer RNA (tRNA). The genetic code in mRNA is read in triplet codons and translated into amino acid sequences.
These general transfers allow genetic information in DNA to be faithfully copied and propagated from cell to cell. They also enable genes to be expressed as functional proteins that carry out cellular activities. The one-way flow of information maintains fidelity.
There are two special transfers that can occur under specific conditions:
1. Reverse transcription: RNA information is copied into DNA, carried out by reverse transcriptase enzymes. This is seen in retroviruses like HIV.
2. RNA replication: RNA is copied into RNA by RNA-dependent RNA polymerases. This is important for some viruses.
These special transfers show that information flow from RNA back to nucleic acids is possible in some cases. However, they require special enzymes not normally present.
There are four unknown transfers that are not thought to occur naturally:
1. Protein directly synthesized from DNA without mRNA intermediate.
2. Protein synthesized directly from another protein template.
3. RNA synthesized directly from a protein template.
4. DNA synthesized directly from a protein template.
The dogma states these information transfers do not occur, i.e. protein sequence cannot provide template information to make nucleic acids or other proteins. This maintains the integrity of the genetic code.
The central dogma is not an absolute law but a general framework. Recent discoveries have revealed additional complexity in cellular information flow:
- Prions can transmit biological information between proteins, causing misfolding.
- Epigenetic changes like DNA methylation can alter gene expression without changing sequence.
- Post-translational modifications expand the information content of proteins.
- RNA editing can alter RNA sequence after transcription.
- Retrotransposons copy RNA back into DNA genome.
However, these exceptions do not fundamentally violate the central dogma's basic premise that information flows from nucleic acids to proteins and not vice versa. The central dogma has been extremely influential in molecular biology research and still provides a guiding framework for information flow. Driving research on the genetic code, transcription, translation. Understanding viral replication mechanisms. Setting the basis for modern biotechnology like PCR, DNA cloning, antibody production. Elucidating disease mechanisms related to gene expression or protein misfolding. And explaining how mutations in DNA can affect phenotypes via altered proteins.
While an oversimplification of the true complexity of molecular biology, the elegance of the central dogma has driven research and discovery for over 60 years. Crick's insightful articulation of this concept was pivotal in the growth of molecular biology in the 20th century.
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