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Keyboards, Codes and the Search for Optimality

In biology, as in technology, we should not confuse persistence with perfection

Robert L. Dorit

Going with What Works

The vagaries of history inform the most fundamental act of living systems: the interpretation of genetic information. The genetic code, the Rosetta stone of all living systems, is hardly the best of all possible codes. Instead, like the QWERTY keyboard, the correspondences between the information in DNA bases and their amino-acid meanings are not optimal, but in the final analysis, are good enough.

Circular diagram of RNA depicts the genetic codeClick to Enlarge ImageThe ribosome, the cellular machinery that synthesizes proteins, reads the information in RNA by interpreting the meaning of non-overlapping but adjacent triplets of bases, the alphabet of this nucleic acid (the well-known A, U, C and G). In one of the most compelling arguments for the common descent of all living organisms, the genetic code—the translation table that matches particular amino acids to particular triplets—is virtually universal. GGG codes for the amino acid glycine in you, in the bacteria in your gut, in the yeast in your bread and in every other living thing. But although the universality of the genetic code speaks to the common ancestry of all life on this planet, it is still not obvious why GGG should code for glycine.

Why does GGG, and not, for example, ACA, code for glycine? Is the universal genetic code simply the result of a random assignment of amino-acid meanings to the 64 possible triplets, or has natural selection operated on the genetic code? A quick inspection of the code answers that question: Natural selection is at work. Thus, for instance, triplets that differ in their third position (such as GGG, GGC or GGA) all code for glycine: The assignment is not random. This pattern, known as the redundancy of the genetic code, acts to temper the effects of the inexorable mutations that occur in DNA. Because of redundancy, between a quarter and a third of mutations in a gene, on average, do not affect the sequence of the resultant protein. Redundancy alone suggests that the genetic code is the result of evolution and not simply the consequence of a random assignment of amino-acid meanings to triplet coding sequences.

Dismissing the idea of random assignments, however, does not mean embracing optimality. The genetic code does indeed contain many features that dampen the impact of mutation on the sequence of proteins and hence, presumably, on the fitness of organisms. But a computer program can come up with hypothetical genetic codes that do a better job of dampening the impact of mutation: The actual genetic code is not ideal; it is good enough. Moreover, the presumption that the genetic code has been shaped solely by a single set of selective forces is just that—presumption. Likewise, when we assert that the genetic code must be optimal, but in ways we do not yet understand, we are skating past the intellectual core of evolutionary biology. A richer narrative suggests that once a functioning genetic code evolved, a complex and interlinked set of biological features, including the entire machinery for protein synthesis, evolved around it and cemented it in place. In effect, the genetic code is nature’s QWERTY keyboard. But unlike the QWERTY keyboard—which could, in theory, be replaced by a better alternative—the genetic code is so embedded in the molecular machinery that evolution will not tolerate its disruption.

Neither our technology nor our biology can evade the hand of history. History underlies the configurations of the QWERTY and the AZERTY keyboards. Within the keyboards, vestiges of an even deeper history remain: The central row preserves traces of the original alphabetical arrangement that existed in the very first typesetting machines.

History, too, accounts for the universality of the genetic code. And here again, even deeper traces of prebiotic evolution can be found: Certain base triplets show particular physical attraction for the amino acids they would eventually come to encode. Everything has a past, though it may sometimes be concealed. The power of the evolutionary perspective resides in its acknowledgment of the importance of that past. Perhaps more subtly, evolutionary logic makes a profound distinction between history and destiny. We may find great comfort in the idea of inexorable progress, but the products of the evolutionary process, like the products of human ingenuity, are not about perfection.

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