Four authors write about the Central Dogma without understanding it

One of the nice things about reading older scientists’ blogs and Twitter feeds is that you get reminded of things you should know and have your own views corrected from their years of experience. One of the things that I’ve seen Larry Moran, professor emeritus at the University of Toronto, write about repeatedly is the Central Dogma of Molecular Biology.

The Central Dogma is a concept that was described by Francis Crick, one of the two scientists who described the structure of DNA, and can be summarised by saying that sequence information can be transferred between nucleic acids or from nucleic acids to protein but never from protein to either protein or to nucleic acid. Or, in graphical form with arrows showing transfer of sequence information:

central-dogma-crick-1970

https://www.nature.com/nature/focus/crick/pdf/crick227.pdf

This simple concept is often misunderstood and, in his own post on the topic, Larry Moran attributes this misunderstanding to a textbook written by James Watson, who described the structure of DNA with Francis Crick, where he erroneously presented the Central Dogma as two step process of DNA to RNA to protein. That misconception has remained. In fact Swedish scientist Per Kraulis found that of eight PhD theses written at his institute that mentioned the Central Dogma, four of them described it incorrectly!

Now aware of these potential issues, I couldn’t help noticing a recent paper in PLOS One which mentions the Central Dogma; A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology. Reading through the abstract and then the paper itself made one thing clear; the authors did not understand the Central Dogma!

The paper starts by saying that the Central Dogma has to be updated to accommodate new discoveries, such as miRNA, and then moves onto dynamically modelling the Central Dogma, using either the old model or their updated model. In the end, they conclude that their new model is more robust and better reflects reality. I will admit that I did not understand their modelling but I highly doubt it offers useful information because the work is based on at least two incorrect assumptions.

First, the Central Dogma describes the possible routes of information transfer. It is not meant to describe a dynamic process and says nothing about the regulation of information transfer or the mechanisms involved therein. The paper’s modelling approach doesn’t make sense from the start because it asks questions that the Central Dogma never attempts to answer.

The second problem is that the authors just do not understand the Central Dogma in the first place. There is an attempt to represent it in their model but that is just a mess. They say they are using the 1965 model but I do not know where they get that date from. The papers they claim to use as a guide for the original model were published in 1961 and 1970. They don’t even have a reference from 1965!

To illustrate, here is the first sentence of the introduction.

In 1965, the pioneering work of Jacob and Monod showed that DNA is transcribed to RNA and further translated into protein, and that the rate of transcription is controlled by a feed- back loop in which protein regulates the activity of the transcriptional complex [1].

Here is reference 1, not published in 1965.

1. Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. Journal of molecular biology. 1961; 3:318–56. PMID: 13718526

Other than their model, the only time that they attempt to describe the Central Dogma is in their conclusion, where they state (emphasis mine).

Although the overall structure of the [Central Dogma] (i.e. information flow from DNA-> RNA->Protein) has remained intact over the past half-century, the complexity of this cascade has surprisingly increased.

That is plain wrong! The Central Dogma is not DNA → RNA → protein! The really crazy part is that they cite Crick’s 1970 clarification of the Central Dogma. The figure earlier in this post is from that paper and directly contradicts their statement! Here is the entire abstract of Crick’s 1970 paper.

The central dogma of molecular biology deals with the detailed reside-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid.

There is no mention of a single, fixed pathway, only that information can not get out of proteins. The scary thing is that not only was this paper published by four scientists who completely misunderstood the concept that they based their entire paper around but that it was similarly misunderstood by both the editor and the reviewers.

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