The fuzzy thinking of John Parrington: The Central Dogma

My copy of The Deeper Genome: Why there's more to the human genome than meets the eye has arrived and I've finished reading it. It's a huge disappointment. Parrington makes no attempt to describe what's in your genome in more than general hand-waving terms. His main theme is that the genome is really complicated and so are we. Gosh, golly, gee whiz! Re-write the textbooks!

You will look in vain for any hard numbers such as the total number of genes or the amount of the genome devoted to centromeres, regulatory sequences etc. etc. [see What's in your genome?]. Instead, you will find a wishy-washy defense of ENCODE results and tributes to the views of John Mattick.

John Parrington is an Associate Professor of Cellular & Molecular Pharmacology at the University of Oxford (Oxford, UK). He works on the physiology of calcium signalling in mammals. This should make him well-qualified to write a book about biochemistry, molecular biology, and genomes. Unfortunately, his writing leaves a great deal to be desired. He seems to be part of a younger generation of scientists who were poorly trained as graduate students (he got his Ph.D. in 1992). He exhibits the same kind of fuzzy thinking as many of the ENCODE leaders.

Let me give you just one example.

Sandwalk readers will be familiar with the correct meaning of the Central Dogma of Molecular Biology. It says ...

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)

This is very clear. It says nothing about the definition of a gene and nothing about whether RNAs can be functional. In fact, Crick was no idiot (gasp!) he knew about tRNA genes and ribosomal RNA genes.

Parrington is one of those scientists who were never taught the real meaning of the Central Dogma. That's sad but it's understandable. However, like many other scientists, he writes about his misconceptions without ever checking the original papers or even thinking seriously about what he says. He promotes the idea that genes are stretches of DNA that encode proteins (no genes for functional RNAs) and that the Central Dogma of Molecular Biology is the basis of this belief.

Thus, the discovery of non-protein information (like RNA) is a paradigm shift that requires a new definition of a gene. There's a sense in which he is correct. Anyone who believes what he believes needs a paradigm shift. However, that shift in thinking should have occurred decades ago and it has nothing to do with the human genome project.

Here's how John Parrington describes the Central Dogma on pages 38-39.

The discovery of the genetic code signalled the primacy of the new discipline of molecular biology. Central to this was Crick's claim that life is a one-way flow of information from DNA to RNA to protein—the 'central dogma of molecular biology.' ...

This is not what Crick meant but, apparently, there are a lot of scientists who think this way. This lead to a great shock for them when they discovered functional RNAs (They were first discovered in the late 1960s and Nobel Prizes were awarded in 1989 for other functional RNAs. Some scientists are a bit behind in their reading.)

John Parrington realized in 2012 that there was something wrong. He writes on pages 91-91 ...

The [ENCODE] study also found that 80 percent of the human genome was generating RNA transcripts. In line with these transcripts having functional importance, many were found in specific cellular compartments, indicating that they have fixed addresses where they operate. Surely there could hardly be a greater divergence from Crick's central dogma than this demonstration that RNAs were produced in far greater numbers across the genome thatn could be expected if they were simply intermediates between DNA and protein. Indeed, some ENCODE researchers argued that the basic unit of inheritance should now be considered as the transcript. So Stamatoyannopoulos claimed that 'the project has splayed an important role in changing our concept of a gene.'

The ENCODE project will, indeed, have done some good if it causes people like Parrington and Stamatoyannopoulos to finally get up to date on their concept of a gene. But, since the modern concept of a gene as "a DNA sequence that is transcribed to produce a functional product" includes functional RNAs as well as proteins, and since that concept is at least forty years old, one wonders why a practicing scientist would want to advertise the fact that they are so out-of-date.

And why would they want to mislead the public?

You may think I'm being unfair. John Parrington isn't the only scientist to misunderstand the Central Dogma. True enough, but most scientists don't write books about it and don't bother to read the relevant papers. Recall that the discovery of reverse transcriptase raised questions about the Central Dogma back in the late 1960s. This prompted Crick to write the Nature paper that corrected any false impressions about refuting the Central Dogma (Crick, 1970). He made it clear that the flow of information from RNA to DNA had nothing to do with the Central Dogma of Molecular Biology. That was allowed in the original 1958 version (Crick, 1958).

But here's how John Parrington describes it on page 118.

The recognition that RNA can code for DNA was one of the the first challenges to Crick's central dogma that the information can only flow in one direction, via RNA to proteins. We saw in Chapter 3 how, since proteins are required to replicate and transcribe DNA, it could equally be valid to see information flowing back to DNA from proteins. Nevertheless, this is information flow in an indirect sense. In contrast, turning an RNA sequence into DNA is a very literal challenge to the central dogma, and this reversal of information requires a specific enzyme—reverse transcriptase.

This is fuzzy thinking and it's just one of many examples in the book. This is why it is such a pain to read and it's why I have no confidence in the conclusions of the author. It's also why I'm going to have such a hard time discussing Parrington's views on junk DNA because those views are colored by deep misunderstandings of fundamental principles of biochemistry and molecular biology. It's going to take as much effort as discussing Jonathan Wells' book [The Myth of Junk DNA by Jonathan Wells]. Maybe I should just have you read those posts from 2011. They pretty much cover all the problems with Parrington's book except for the ENCODE stuff.

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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]