In previous essays (here, here, and here), we have surveyed various aspects of the genetic code that appear to be highly optimized. So strong is the appearance of fine-tuning that it can hardly be a random accident. We are thus left with two choices — either the genetic code is the result of trial and error, driven by natural selection, or else it is the product of conscious design. In this final post, I will evaluate which of these options is the more likely.
Locked in Place
As I wrote in a previous article on the optimized set of the twenty commonly used amino acids found in life, once the genetic code is established, and each amino acid is tied to specific codons, tRNAs, and aminoacyl-tRNA synthetases, it becomes essentially locked in place — that is to say, it becomes evolutionarily entrenched (notwithstanding the fact that there are occasional extremely minor variations on the standard code). Indeed, making significant modifications to the code would wreak havoc on the cell, since reassigning relationships between codons and amino acids would affect every polypeptide made by the cell.
Some have tried to argue around this by positing that the lesser-used codons can be redesignated to a different but related amino acid, thus allowing the genetic code to become optimized. There are, however, significant difficulties with this proposal. For one thing, it seems highly unlikely that by virtue of replacing some of the lesser-used amino acid assignments with a related amino acid that one could attain the level of optimization which we find in the conventional code.
Furthermore, the question is naturally raised as to what selective utility would be exhibited by the new amino acids. Indeed, they would have no utility until incorporated into proteins. But that won’t happen until they are incorporated into the genetic code. And thus they must be synthesized by enzymes that lack them. And let us not forget the necessity for the dedicated tRNAs and activating enzymes which are needed for including them in the code.
A Related Difficulty
One related difficulty with standard evolutionary explanations is that a pool of biotic amino acids substantially less than 20 is liable to substantially reduce the variability of proteins synthesized by the ribosomes. And prebiotic selection is unlikely to sift the variational grist for this trait of amino-acid-optimality prior to the origin of self-replicative life (in many respects, “prebiotic selection” is somewhat oxymoronic).
There is the added problem of the potential for codon mapping ambiguity. If, say, 80 percent of the time a particular codon specifies one amino acid and 20 percent of the time it specifies another, this mapping ambiguity would lead to cellular chaos.
For a thorough discursive review of various attempts at explaining code evolution, I refer readers to a review paper by Eugene Koonin and Artem Novozhilov.1 They conclude their critical review by lamenting that,
In our opinion, despite extensive and, in many cases, elaborate attempts to model code optimization, ingenious theorizing along the lines of the coevolution theory, and considerable experimentation, very little definitive progress has been made.
They further report,
Summarizing the state of the art in the study of the code evolution, we cannot escape considerable skepticism. It seems that the two-pronged fundamental question: “why is the genetic code the way it is and how did it come to be?,” that was asked over 50 years ago, at the dawn of molecular biology, might remain pertinent even in another 50 years. Our consolation is that we cannot think of a more fundamental problem in biology.
Nonetheless, even if we grant the premise that the genetic code can be modified over time, it still remains to be determined whether there are sufficient probabilistic resources at hand to justify appeals to the workings of chance and necessity. In view of the sheer number of codes that would need to be sampled and evaluated, evolutionary scenarios seem quite unlikely.
The Combinatorial Space Problem
The combinatorial space of genetic codes is astronomically large — conservatively, this may be estimated to be on the order of 1018 to 1020. This assumes that codon group sizes are fixed — i.e., how many codons are assigned to each respective amino acid. It also assumes that the set of amino acids used by life is limited to the standard twenty. Without either of these presumptions, the combinatorial space is many orders of magnitude larger.
To give a sense of the vastness of this combinatorial space, consider that, in order to arrive at the standard genetic code found in nature by random sampling, this would require more than 800 genetic codes to be sampled every second between the origin of life and the present day. Although we do not currently have a precise estimate of how prevalent are genetic codes that are as optimized as the canonical code, it is likely to be quite rare. To put this in perspective, if we assume, conservatively, that the prevalence of codes as highly optimized as the conventional code is one in ten billion (though the actual prevalence is likely to be significantly less than this), in a million-year time window a genetic code would need to be sampled every fifty-three minutes in order to stumble upon, by chance, one of those codes. It is extremely doubtful that this could be achieved by a random search given the strong pressure against modifications to the code after it has been established.
No Frozen Accident
Though Francis Crick asserted that the genetic code is a “frozen accident,”2 the evidence now overwhelmingly reveals that the standard code is highly optimized across multiple constraints. For the reasons discussed above, it is highly improbable that the genetic code could have evolved by gradual trial and error. Given our knowledge of the kinds of effects that are produced by intentional causes, the incredible and multifaceted fine-tuning is far more probable on the supposition of conscious intent. The genetic code’s optimality therefore points forcefully in the direction of an intelligent creator.
Notes
- Koonin EV, Novozhilov AS. Origin and evolution of the genetic code: the universal enigma. IUBMB Life. 2009 Feb;61(2):99-111. doi: 10.1002/iub.146. PMID: 19117371; PMCID: PMC3293468.
- Crick FH. The origin of the genetic code. J Mol Biol. 1968 Dec;38(3):367-79. doi: 10.1016/0022-2836(68)90392-6. PMID: 4887876.