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Monday, December 10, 2007

SEED and the Central Dogma of Molecular Biology - I Take Back My Praise

On October 1, 2007 I praised SEED magazine for being one of the few science magazines to correctly define the Central Dogma of Molecular Biology. Here's what I said two months ago.

One of my pet peeves is the misuse of the term "Central Dogma of Molecular Biology" [Basic Concepts: The Central Dogma of Molecular Biology]. Most people define it as the flow of information from DNA to RNA to protein. Many then go on to declare that the Central Dogma has been overthrown because of reverse transcriptase, alternative splicing, microRNA, epigenetics, or whatever.

This month's issue of SEED has a tear-out summary (cribsheet) of "Genetics." In one of the boxes titled "The Central Dogma of Molecular Biology" there's a drawing of the major pathways of information flow [Cribsheet #12]. The caption says.
There are nine ways information can theoretically flow between DNA, RNA, and protein. Of these, three are seen throughout nature, DNA to DNA (replication), DNA to RNA (transcription), and RNA to protein (translation). Three more are known to occur in special circumstances like viruses or laboratory experiments (RNA to RNA, RNA to DNA, and DNA to protein). Flows of information from protein have not been observed. The trend is clear: information flow from DNA or RNA into protein is irreversible. This is known as the "central dogma," and forms the foundation of molecular biology.
Yeah! As far as I know this is the only popular magazine to get it right.

I take it all back.

This month's issue has an article by Philip Ball outlining another revolution in molecular biology that overthrows the Central Dogma of Molecular Biology. This time it's microRNAs that have done the dirty deed [Redefining Genes].

Philip Ball is a London (UK) based freelance science writer with a Ph.D. in Physics. He has written 10 books on science and many articles for the news section of Nature. Philip Ball blogs at homunculus.

Here's what he says on page 29 of the current newsstand issue of SEED.
For nearly 50 years, the central dogma of molecular biology has been that genetic information is contained within DNA and is passed by rote transcription through RNA to make proteins. ...

The central dogma is being eroded, and it now appears as if DNA's cousin, the humble intermediary RNA, plays at least an equal role in genetics and the evolution of the species.
Philip Ball then gives two recent examples of work showing the involvement of noncoding RNA in gene expression. Then comes the revolution ...
These and a host of other recent findings are rewriting the textbooks of molecular biology. They are beginning to show not only that RNA is more fundamental to genetics than once believed, but also that it can directly affect evolution and elucidate the differences between species. The result is a story that looks a lot messier, but potentially a lot more interesting, than anyone ever guessed.
This is deeply insulting to all biochemists and molecular biologists. What in the world must people like Ball be thinking of us when he writes such nonsense? Does he really believe that for over half a century we have been slavishly adhering to the dogma that genes only make proteins? I know lots of scientists who think the Central Dogma refers to the general pathway of information flow (DNA → RNA → protein) but I never met a biochemist or a molecular biologist who thought that this pathway ruled out genes whose final product was RNA.

That idea is total nonsense, of course, and Philip Ball would know this if he only bothered to read any of the textbooks of molecular biology. Not only have we been teaching about ribosomal RNA, and transfer RNA for 40 years, we've also covered all of the small RNAs involved in splicing, telomeres, signal recognition particle, RNAse P etc. etc. Does he think we're completely ignorant of the Nobel Prizes awarded to Sidney Altman and Tom Czech in 1989 "for their discovery of catalytic properties of RNA"?

Furthermore, we've been teaching about regulatory RNAs for almost as long. The classic examples are the antisense RNAs in bacteriophage λ, attenuation in the trp operon and small RNAs that control the initiation of DNA replication at plasmid origins.

If you were to believe Philip Ball, molecular biologists have clung to his version of the Central Dogma of Molecular Biology in spite of all these counter-examples. Only now are they waking up to the fact that some genes make RNA as their final product. How stupid is that?

Science writers have a special obligation when writing for a general audience. Not only do they have to explain things in simple language but they have to be accurate as well. Pert of being accurate in science is having enough knowledge of the subject to be able to sort out the hype from reality. Philip Ball does not know anough about molecular biology to make that call. He should have read the cribsheet.


Andrew said...

At U of T, I haven't taken a single course that presented the Central Dogma correctly. Everybody (except you, obviously) seems to think it's DNA-->RNA-->protein.

For example, Malcolm Campbell got it wrong in BIO250. The course website is; go to Lectures (on left hand side); Part 2; and look at lecture 1, slides 2 and 3. He is of the opinion that the "central dogma" is wrong and needs to be "elaborated" upon.

Ian B Gibson said...

It looks like Wikipedia gets it right:

The central dogma of molecular biology was first enunciated by Francis Crick in 1958[1] and re-stated in a Nature paper published in 1970:[2]

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 back from protein to either protein or nucleic acid.

In other words, 'once information gets into protein, it can't flow back to nucleic acid.'

Interestingly, have the above definition listed under 'central dogma (molecular biology)', but the following definition listed under 'central dogma (genetics)':

The concept, subject to several exceptions, that genetic information is coded in self-replicating deoxyribonucleic acid and undergoes unidirectional transfer to messenger ribonucleic acids in transcription that act as templates for protein synthesis in translation.

Steve LaBonne said...

Eh, I'm still impressed that SEED got it right even once. That virtually never happens in popular science writing of any kind.

Larry Moran said...

It looks like Wikipedia gets it right:

I was the one who edited the original incorrect Wikipedia entry. Note that while Wikipedia gets it right in the first paragraph the article becomes confused later on.

Larry Moran said...

Post-Diluvian Diaspora said...

At U of T, I haven't taken a single course that presented the Central Dogma correctly. Everybody (except you, obviously) seems to think it's DNA-->RNA-->protein.

That's pretty sad, isn't it? What it shows you is that your Professors are just copying from the textbooks without doing any checking on their own.

It's especially sad when they go on to say that the "Central Dogma of Molecular Biology" is wrong! That's totally illogical. Either it really is a correct central dogma, in which case their definition must be wrong, or it's an incorrect central dogma, in which case molecular biologists must be idiots.

Normally when faced with such a paradox you'd expect scientists to do a bit of research on the Central Dogma of Molecular Biology. It's not that hard—if you Google "Central Dogma of Molecular Biology" you find that the top three results are wrong but the fourth leads you to Crick's original paper. (The fifth brings you here.)

Larry Moran said...

Steve Labonne says,

Eh, I'm still impressed that SEED got it right even once. That virtually never happens in popular science writing of any kind.

Pretty sad, isn't it, when we have to be "impressed" with a "science" magazine that gets something right about one time out of ten?

Wavefunction said...

So what would you say is the best and most readable science magazine out there?

MarkH said...

I remember I was taught it incorrectly in undergrad and in graduate school. I misquoted it myself and a commenter pointed me to your explanation, so I finally have it right - shortly before receiving a PhD in molecular physiology.

It's a problem in science. We tend to get taught a narrow window of science, and the correct history is underemphasized in the rush to teach you to hold a pipette.

Steve LaBonne said...

asutosh- I think they all suck. There hasn't been a good one since the palmy days of Scientific American- the likes of which we'll probably never see again.

The best general-audience science writing is in books, and (with rare exceptions like Carl Zimmer), specifically in books written by practicing scientists.

Unknown said...

Two serious knocks on this crappy article. One, microRNAs are just switches. A switch does very little to overturn the Central Dogma.

Two, the Pruitt/Purdue/Arabidopsis story is much, much better explained as pollen contamination rather than Dogma-defying magic.