Crick’s Central Dogma and Closed Causal Loops

A recent article in the Journal of Biology, entitled “Small changes, big results: evolution of morphological discontinuity in mammals” [1], discusses how significant phenotypic changes appear to often be the result of variations of gene expression due to regulatory controls, instead of as a direct result of the primary sequence per se of the DNA:

Rather than simple mutations within structural genes, many of the mechanisms underlying change represent more subtle and complex changes involving gene regulation. Complex anatomical differences such as those defining the higher categories of mammals, as well as differences between more closely related species, are likely to be the result of interacting pathways that regulate gene expression during development. Changes in gene regulation seem important for a host of phenotypic differences in mammals and other organisms. In addition, phenotypic change could result from changes such as expansion and contraction of gene families or alternative splicing of RNA transcripts.

If this is so, then it seems to be evidence that genome, as the forcer of phenome, cannot be directly equated with ‘amino acid sequence of a polypeptide’. This in turn led me to wonder: how do such results either agree or conflict with the Central Dogma, which makes some important assertions regarding these sequences?

Crick’s Central Dogma

The Central Dogma was first enunciated by Crick in 1958 [2], and then again in 1970 [3]. It was summarized by Crick (1970, Fig. 2) in a diagram like this one:

centraldogma

Central Dogma

Briefly, the Central Dogma asserts that, of all the possible pathways for information transfers between DNA, RNA and proteins in an organism, that the solid arrows above indicate the probable transfers which occur, and the dashed arrows indicate possible transfers. The notable claim in the Central Dogma is the lack of arrows from proteins back to either RNA or DNA. That is, as Crick explains, the Central Dogma is primarily a negative assertion: that information transfers do not occur from proteins to either RNA or DNA.

Now, a couple of points are in order, which Crick explicitly points out to the reader:

  1. His discussion is only about transfers of sequential information in the primary structure, and the discussion intentionally sets aside any issues of information transfer related to tertiary structures.

  2. His discussion does not say anything about the specific mechanisms of the transfers.

  3. The Central Dogma is intended to apply to current organisms, and is not intended to be applied to origin-of-life processes.

  4. His discussion “says nothing about control mechanisms – that is, about the rate at which the processes work.”

Thus, despite using the term “Dogma”, Crick’s claims were actually fairly cautious and well-delineated.

Controls on Transfers

Now, going back to point 4 – that the Central Dogma says nothing about control mechanisms – leads us to the next step. The information transfers in the above diagram do not explicitly include such controls, but we can add them in, symbolically, by augmenting the original diagram as below:

centraldogma-eff

The red arrows indicate the control forcings on the various transfers. Another way to write this is that each transfer is of the form:

f:X ® Y

where X and Y are the source and destinations of the transfer, respectively, and f indicates the forcing.

 However, the forcings themselves are not fixed, as noted in the J. Biol. article, and it is not only that the genes are regulated, but that the picture is more complicated and it must include a capacity for “changes in gene regulation”. Essentially, the forcings themselves are parameterized. We can show this by further augmenting the diagram:

centraldogma-eff-for

Here the blue arrows symbolically indicate the parameters of the forcings, which modulate the rates of the information transfer in the original diagram. Again, we can write this as follows:

fφ:X ® Y

where φ indicates the parameters of the forcing f.

Entailment and Genome

Our diagram is now much more involved and elaborate. Yet, it illustrates, I think, that Crick’s Central Dogma is quite compatible with the view expressed in the J. Biol. article. Further, we can now say that the information transfers, and the resulting phenotypes, are entailed in the organism by virtue of the additional arrows in this augmented diagram.

We see also now that ‘genome’ is more closely identified with “fφ:X” than with, for example, “the primary sequence of X”. This is also evident in the intuitive sense that if genome is to be a forcer of phenome, then genome must be identified with an active agent in the organism, rather than be identified with a passive alphabetic sequence.

Closed Causal Loops

However, it should also be clear from our augmented diagram that the picture is still quite incomplete, even on this level of abstraction. In particular, since the blue and red arrows are posited as existing within and arising from within the organism itself, it must logically be the case that they can, in turn, be entailed within the organism. Clearly, if we simply keep tacking on arrows (e.g., “f is entailed by g which is entailed by h…”), then an infinite regress will result, which cannot happen since an organism possesses only a finite number of molecules. Therefore, there must exist loops of causal entailments in the organism. Systems which possess these kinds of closed loops of entailment are called “complex” in Rosen’s terminology, and the properties of this kind of complexity have many ramifications for the study of such systems, as described in Rosen’s books, such as [4, 5] and elsewhere on this website.

References

[1] Honeycutt, Rodney L. 2008. “Small changes, big results: evolution of morphological discontinuity in mammals”. J. Biol. 7:9. doi:10.1186/jbiol71. [Article]

[2] Crick, Francis. 1958. “On Protein Synthesis”. Symp. Soc. Exp. Biol. XII, 139-163. [PDF of draft notes]

[3] Crick, Francis. 1970. “Central Dogma of Molecular Biology”. Nature 227:561-563. [PDF]

[4] Rosen, R. 1991. Life Itself. Columbia Univ. Press

[5] Rosen, R. 2000. Essays on Life Itself. Columbia Univ. Press

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3 Responses to Crick’s Central Dogma and Closed Causal Loops

  1. Your analysis is interesting, and underlines more similarity between the central dogma and Rosen’s ideas than I had suspected. So far as your main question is concerned, I wonder if you know of Barbieri’s book The Organic Codes (Cambridge University Press). I read it for the first time about two years ago, and am in the process of reading again now, much more slowly than the first time, and am picking many details that I originally missed.

    He argues that the genetic code and human language is are just the two extreme cases of a whole series of about ten different codes used by living organisms, and that the major changes in life occurred with the introduction of new ways of storing information. This is obviously true, I think, for human language, but more controversial for the other examples. However, his arguments are interesting and worth reading; for example, he explains the Cambrian explosion — with all the metazoan phyla that we know today appearing more or less simultaneously — in terms of of the appearance of a new code, one that allowed “body plans” to be stored in memory.

  2. Tim Gwinn says:

    I’m not familiar with Barbieri’s book — but I think I’ll definitely have to take a look at it! It also looks like he has a new (March ’08) book out, “Introduction to Biosemiotics: The New Biological Synthesis”.

    Semiotics in general is a topic I’ve never quite found convincing, but I’m also not sure I’ve ever read a good exposition of it either.

  3. Barry McKenna says:

    The concept of regulatory controls would seem to be of great interest today. However, according to Google Scholar, there have yet to be any papers citing this work. It is not my intent to imply that the paper is of no value. Rather, I am interested in any thoughts you might have as to why this paper appears to have attracted little interest.