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Ode to the Code

Brian Hayes

The genetic code was cracked 40 years ago, and yet we still don't fully understand it. We know enough to read individual messages, translating from the language of nucleotide bases in DNA or RNA into the language of amino acids in a protein molecule. The RNA language is written in an alphabet of four letters (A, C, G, U), grouped into words three letters long, called triplets or codons. Each of the 64 codons specifies one of 20 amino acids or else serves as a punctuation mark signaling the end of a message. That's all there is to the code. But a nagging question has never been put to rest: Why this particular code, rather than some other? Given 64 codons and 20 amino ­acids plus a punctuation mark, there are 1083 possible genetic codes. What's so special about the one code that—with a few minor variations—rules all life on Planet Earth?

The canonical nonanswer to this question came from Francis Crick, who argued that the code need not be special at all; it could be nothing more than a "frozen accident." The assignment of codons to amino acids might have been subject to reshuffling and refinement in the earliest era of evolution, but further change became impossible because the code was embedded so deeply in the core machinery of life. A mutation that altered the codon table would also alter the structure of every protein molecule, and thus would almost surely be lethal. In other words, the genetic code is the qwerty keyboard of biology—not necessarily the best solution, but too deeply ingrained to be replaced or improved.

There has always been resistance to the frozen-accident theory. Who wants to believe that the key to life is so arbitrary and ad hoc? And there is evidence that the accident is not quite frozen. Certain protozoa, bacteria and intracellular organelles employ genetic codes slightly different from the standard one, hinting that changes to codon assignments are not impossible after all. And if the code is subject to change, then it must also be subject to natural selection, which in turn suggests the possibility of ongoing improvement. Perhaps ours is not the very best of all possible codes, but after four billion years of evolution it ought to be a pretty darn good one.

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The urge to find something singular and superlative about the code was already evident even before it was deciphered. For several years before experiments began to reveal the true structure of the genetic code, theorists were at liberty to dream up codes of their own. Some of the proposals were so ingenious that the real code seemed a bit disappointing. An earlier column in this series (January-February 1998) described that era of imaginary genetic engineering. But the creative thinking did not end with the publication of the codon table; indeed speculation seems to have been inhibited very little by the constraints of mere fact. This sequel is meant to bring the story up to date, covering both the biological mainstream and a few ideas from wilder shores.

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