The Central Dogma Strawman

Whenever you're trying to promote a new idea it's nice to have a scapegoat to beat up on. You're going to get a lot more attention if you can demonstrate that your latest results overthrow some key scientific concept that everyone took for granted. If you can't find a real "key concept" then the next best thing is to make one up.

For the past several decades that strawman target has been The Central Dogma of Molecular Biology. The Central Dogma is supposed to represent the key concept of molecular biology yet it gets "overthrown" on a regular basis every six months. Isn't that strange?

The latest example comes from a Nature review of a recent Science paper. The Science paper presents evidence that many mRNA sequences differ from the sequences in the exons that encode them (Li et al., 2011). RNA editing has been known for decades and every few years it is trotted out again as proof that the Central Dogma is wrong. The recent Li et al. (2011) paper doesn't present evidence for a new phenomenon but it does suggest that RNA editing may be much more common than previously suspected.

Here's what Nature staff writer Erika Check Hayden says about this paper ("Cells may stray from 'central dogma'" Hayden, 2011a).

All science students learn the 'central dogma' of molecular biology: that the sequence of bases encoded in DNA determines the sequence of amino acids that makes up the corresponding proteins. But now researchers suggest that human cells may complicate this tidy picture by making many proteins that do not match their underlying DNA sequences.

Now if that really was what the Central Dogma actually said then it would have disappeared thirty years ago.

The real Central Dogma of Molecular Biology is ...

... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

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. (F.H.C. Crick, 1970)

I've explained why this is the correct version in an old blog posting from 2007: Basic Concepts: The Central Dogma of Molecular Biology. A very similar definition can be found on the Wikipedia site: Central Dogma of Molecular Biology. The key point is that once information flows into protein it can't flow back to nucleic acid. The standard misconception of the Central Dogma is actually the normal information flow pathway or what Crick called the "Sequence Hypothesis." It's a generality that was never meant to be an inviolate rule like the actual Central Dogma.

Hayden has another article in this week's print version of Nature (Hayden, 2011b). The second article emphasizes the controversy surrounding the Li et al. (2011) paper—lots of people are skeptical—but she doesn't back off the implications.

If verified, the findings would require a rewrite of the 'central dogma' of molecular biology, which posits that the RNA transcripts that carry genetic information to the ribosome, where they are used as templates for protein assembly, are generally faithful matches to the original DNA.

There are two remarkable things about such a statement. First, RNA editing has been an established fact for almost thirty years so if the Central Dogma needed rewriting it would have been done a long time ago. Second, Hayden was informed in the comments to her first article that there was a problem with her definition of the Central Dogma. Maybe she didn't have time to change the second version that was about to be published.

To be fair, this isn't just a problem with science writers who don't do their homework. Hayden is right when she says that most science students learn an incorrect version of the Central Dogma of Molecular Biology. It's true that most textbooks promote the information flow pathway as the Central Dogma and they fail to point out that the real version only precludes reverse translation. I don't understand why so many textbook writers and teachers continue to teach something they know to be false as the "Central Dogma" of molecular biology.

Is it because they don't know about the exceptions?

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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]

Hayden, E.C. (2011a) Cells may stray from 'central dogma.' Nature Published online 19 May 2011 [doi:10.1038/news.2011.304.

Hayden, E.C. (2011a) Evidence of altered RNA stirs debate. Nature 473:432. [doi:10.1038/473432a]

Li, M., Wang, I.X., Li, Y., Bruzel, A., Richards, A.L., Toung, J.M., and Cheung, V.G. (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome. Science. 2011 May 19. [Epub ahead of print] [Science]