Is the coding metaphor relevant for the genome?

I have argued that the neural coding metaphor is highly misleading (see also similar arguments by Mark Bickhard in cognitive science). The coding metaphor is very popular in neuroscience, but there is another domain of science where it is also very popular: genetics. Is there a genetic code? Many scientists have criticized the idea of a genetic code (and of a genetic program). A detailed criticism can be found in Denis Noble’s book “The music of life” (see also Noble 2011 for a short review).

Many of the arguments I have made in my essay on neural coding readily apply to the “genetic code”. Let us start with the technical use of the metaphor. The genome is a sequence of DNA base triplets called “codons” (ACG, TGA, etc). Each codon specifies a particular amino-acid, and proteins are made of amino-acids. So there is a correspondence between DNA and amino-acids. This seems an appropriate use of the term “code”. But even it in this limited sense, it should be used with caution. The fact that a base triplet encodes an amino-acid is conditional on this triplet being effectively translated into an amino-acid (note that there are two stages, transcription into RNA, then translation into a protein). But in fact only a small fraction of a genome is actually translated, about 10% (depending on species); the rest is called “non-coding DNA”. So the same triplets can result in the production of an amino-acid, or they can influence the translation-transcription system in various ways, for example by interacting with various molecules involved in the production of RNA and proteins, thereby regulating transcription and translation (and this is just one example).

Even when DNA does encode amino-acids, it does not follow that a gene encodes a protein. What might be said is that a gene encodes the primary structure of proteins, that is, the sequence of amino-acids; but it does not specify by itself the shape that the protein will take (which determines its chemical properties), the various modifications that occur after translation, the position that the protein will take in the cellular system. All of those crucial properties depend on the interaction of the product of transcription with the cellular system. In fact, even the primary structure of proteins is not fully determined by the gene, because of splicing.

Thus, the genome is not just a book, as suggested by the coding metaphor (some have called the genome the “book of life”); it is a chemically active substance that interacts with its chemical environment, a part of a larger cellular system.

At the other end of the genetic code metaphor, genes encode phenotypes, traits of the organism. For example, the gene for blue eyes. A concept that often appears in the media is the idea of genes responsible for diseases. One hope behind the human genome project was that by scrutinizing the human genome, we might be able to identify the genes responsible for every disease (at least for every genetic disease). Some diseases are monogenic, i.e., due to a single gene defect, but the most common diseases are polygenic, i.e., are due to a combination of genetic factors (and generally environmental factors).

But even the idea of monogenic traits is misleading. There is no single gene that encodes a given trait. What has been demonstrated in some cases is that mutations in a single gene can impact a given trait. But this does not mean that the gene is responsible by itself for that trait (surprisingly, this fallacy is quite common in the scientific literature, as pointed out by Yoshihara & Yoshihara 2018). A gene by itself does nothing. It needs to be embedded into a system, namely a cell, in order to produce any phenotype. Consequently, the expressed phenotype depends on the system in which the gene is embedded, in particular the rest of the genome. There cannot be a gene for blue eyes if there are no eyes. So no gene can encode the color of eyes; this encoding is at best contextual (in the same way as “neural codes” are always contextual, as discussed in my neural coding essay).

So the concept of a “genetic code” can only be correct in a trivial sense: that the genome, as a whole, specifies the organism. This clearly limits the usefulness of the concept, however. Unfortunately, even this trivial claim is also incorrect. An obvious objection is that the genome specifies the organism only in conjunction with the environment. The deeper objection is that the immediate environment of the genome is the cell itself. No entity smaller than the cell can live or reproduce. The genome is not a viable system, and as such it cannot produce an organism, nor can it reproduce. An interesting experiment is the following: the nucleus (and thus the DNA) from an animal cell is transferred to the egg of an animal of another species (where the nucleus has been removed) (Sun et al., 2005). The “genetic code” theory would predict that the egg would develop into an animal of the donor species. What actually happens (this was done in related fish species) is that the egg develops into some kind of hybrid, with the development process closer to that of the recipient species. Thus, even in the most trivial sense, the genome does not encode the organism. Finally, since no entity smaller than the cell can reproduce, it follows that the genome is not the unique basis of heritability – the entire cell is (see Fields & Levin, 2018).

In summary, the genome does not encode much except for amino-acids (for about 10% of it). It should be conceptualized as a component that interacts with the cellular system, not as a “book” that would be read by some cellular machinery.

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