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Wednesday, October 07, 2009

The Ribosome and the Central Dogma of Molecular Biology

The Nobel Prize website usually does an excellent job of explaining the science behind the prizes. The STRUCTURE AND FUNCTION OF THE RIBOSOME is a good explanation of reasons why the 2009 Nobel Prize in Chemistry was awarded for work on the ribosome.

Unfortunately, the article begins by perpetuating a basic misunderstanding of the Central Dogma of Molecular Biology.
The ribosome and the central dogma. The genetic information in living systems is stored in the genome sequences of their DNA (deoxyribonucleic acid). A large part of these sequences encode proteins which carry out most of the functional tasks in all extant organisms. The DNA information is made available by transcription of the genes to mRNAs (messenger ribonucleic acids) that subsequently are translated into the various amino acid sequences of all the proteins of an organism. This is the central dogma (Crick, 1970) of molecular biology in its simplest form (Figure 1)

This is not the Central Dogma according to Crick (1970). I explain this in a posting from two years ago [Basic Concepts: The Central Dogma of Molecular Biology].

In both his original paper (Crick, 1958) and the 1970 update, Crick made it very clear that the Central Dogma of Molecular Biology is ....
The Central Dogma. This states that once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.
The diagram that's usually attributed to the central dogma is actually the Sequence Hypothesis. Crick was well aware of the confusion and that's why he wrote the 1970 paper. It was at a time when the so-called "Central Dogma" had been "overthrown" byt the discovery of reverse transcriptase.

Since then the false version of the Central Dogma has been disproven dozens and dozens of times—it's a minor cottage industry.

Here's what Crick says about this false version of the Central Dogma in his 1970 paper—the one quoted at the top of this page.
It is not the same, as is commonly assumed, as the sequence hypothesis, which was clearly distinguished from it in the same article (Crick, 1958). In particular, the sequence hypothesis was a positive statement, saying that the (overall) transfer nucleic acid → protein did exist, whereas the central dogma was a negative statement saying that transfers from protein did not exist.
Let's try and get it right. It will have the great benefit of stopping us from putting up with any new papers that refute the Central Dogma of Molecular Biology!

It will also encourage critical thinking. Haven't you ever wondered why there is a Central Dogma when reverse transcriptase, splicing, epigenetics, post-translational modification, chromatin rearrangements, small regulatory RNAs, and just about everything else under the sun, supposedly refutes it?

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163,

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]


  1. Thanks, Larry! I had no idea about any of it.

    To quote Crick:
    "but transfer from protein to protein, or from protein to nucleic acid is impossible".

    My first thought was "the structural information is transferred from protein to protein in the case of prions". To see what exactly Crick meant (I think he implied precise sequence information), I went to read his 1970 paper and there I find yet another reason why Crick is a scientific god of mine:

    "There is, for example, the problem of the chemical nature of the nature of the disease scrapie"

    Never knew about Crick having a foot in this. What a brilliant mind! Made my day.

  2. Thanks! I wondered about the Nobel summary's use of "central dogma." Obviously it was wrong, and we have it straight from the horse's mouth.

    It was great fun to read Crick's 1970 paper, which is later enough to be able to put the struggles of the early days in historical perspective. Like DK, I found it fascinating that he recognized the specialness of what we would now call prion diseases, and thought they might turn out to be a potential real exception to the dogma, although my understanding is that no one things that sequence information is passing from protein to protein.