Central dogma of molecular biology

The central dogma of molecular biology is a hypothesis published by Francis Crick in 1958 about the possible flow of information between the biopolymers DNA , RNA and protein . It describes the transmission of information that is determined by the order ( sequence ) of monomers ( nucleotides in DNA and RNA, amino acids in proteins).

In Crick's original form, the hypothesis states:

Once (sequential) information has been translated into a protein, it cannot get out of there.

In 1970 Crick gave an alternative formulation of the dogma:

Sequential information cannot be transferred from protein to protein or to nucleic acid.

The central dogma - even if there are critical voices - is widely accepted and is still regarded today as one of the cornerstones of molecular biology.

Crick later regretted the name dogma , which is unusual in natural science , because he did not intend to formulate a doctrine with irrefutable truth. In 1976 he said, “I just didn't know what dogma meant. And I could just as easily have called it Central Hypothesis ... Dogma was just a catchphrase. "

Types of information transfer

Types of transmission of sequential information permitted according to the Central Dogma. There was no evidence for the transfer represented by dashed arrows in 1958.

According to Crick (1970), the nine theoretically possible types of transmission of sequential information between DNA, RNA and protein can be divided into three areas: The general types of transmission occur in every cell with rare exceptions. The existence of special types of transmission is known, but these only occur under certain conditions / in certain organisms. The existence of the remaining types of transmission, however, could not be shown until today and would refute the central dogma.

General types of transmission

• DNA → DNA: replication
• DNA → RNA: transcription
• RNA → protein: translation

Special types of transmission

• RNA → RNA: RNA replication , happens e.g. B. in RNA viruses (example: poliovirus ) by RNA-dependent RNA polymerases and in viroids
• RNA → DNA: reverse transcription , happens e.g. B. in retroviruses by the enzyme reverse transcriptase or in eukaryotes by telomerase
• DNA → protein: Direct translation from DNA to protein, has been demonstrated in vitro in cell-free environments.

Unknown modes of transmission forbidden according to the Central Dogma

• Protein → DNA
• Protein → RNA
• Protein → protein

reception

The central dogma of molecular biology has been repeatedly criticized since its formulation and declared obsolete.

In many textbooks, however, the dogma is not presented in the version intended by Crick, but in a more restrictive version, which comes from James Watson's textbook Molecular Biology of the Gene and says that sequential information is transferred from DNA via RNA to protein and thus only includes the general types of transmission . This simplified version describes the typical process of information transfer, but it is understood as a general "dogma" not applicable, as Crick also noted. Many “refutations” of the Central Dogma are based on this misunderstanding.

However, several arguments were also put forward against the central dogma in Crick's original version, including the following: Prions were initially suspected as an example of a “forbidden” type of protein-protein information transfer. However, according to current research, prions are proteins that can change the conformation of other proteins and thus do not transmit any sequential information.

Representatives of systems biology emphasize various regulatory feedback mechanisms from proteins to nucleic acids, which make it necessary to treat a cell as a complex network in which information transfer of a sequential nature does not play a significant role. From this point of view, the central dogma describes only part of the flow of information. What is criticized, however, is that it is used to justify a reductionist research methodology that seeks to understand organisms in a bottom-up approach, starting with the genes.

literature

• F. Crick: On Protein Synthesis . Symp. Soc. Exp. Biol. XII (1958). PMID 13580867 . pdf
• F. Crick: Central Dogma of Molecular Biology . Nature 227: 561-563 (1970). PMID 4913914 . doi : 10.1038 / 227561a0 .
• D. Thieffry, S. Sarkar: Forty years under the central dogma . Trends Biochem. 23, pp. 312-316. PMID 9757833 . doi : 10.1016 / S0968-0004 (98) 01244-4 .

swell

1. ↑ "once (sequential) information has passed into protein it cannot get out again", Crick (1958)
2. ^ "It states that information cannot be transferred back from protein to either protein or nucleic acid." Crick (1970)
3. ↑ Thieffry, Sarkar. P. 315
4. ↑ I just didn't know what dogma meant. And I could just as well have called it the Central Hypothesis… Dogma was just a catch phrase. After Thieffry, Sarkar. P. 313
5. ↑ BJ McCarthy and JJ Holland: Denatured DNA as a Direct Template for in vitro Protein Synthesis. PNAS 54, 880-886 (1965)
6. ↑ MS Bretscher: Direct Translation of a Circular Messenger DNA . Nature 220, 1088-1091 (1968)
7. ^ JD Watson: Molecular Biology of the Gene , WA Benjamin (1965)
8. ^ Thieffry, Sarkar: p. 315
9. ^ Laurence A. Moran: Basic Concepts: The Central Dogma of Molecular Biology. January 15, 2007, accessed November 21, 2013 . 
10. ↑ See Thieffry, Sarkar
11. ^ E. Werner: Genome Semantics, In Silico Multicellular Systems and the Central Dogma . FEBS Letters 579, 1779–1782 (2005)
12. ↑ Thieffry, Sarkar p. 316
13. ^ D. Noble: Claude Bernard, the first systems biologist, and the future of physiology . Experimental Physiology 93.1, pp. 16-26 (2007)