This article is a brief introduction and commentary relating to a new paper appearing on the “Biology Worthy of Life” website: “Look What’s Happened to Genetic Synonyms!”
Following immediately upon the discovery of the double helical structure of DNA in 1953, some of the most brilliant scientists from several disciplines pooled their efforts in a feverish quest to lay bare the secret of the “genetic code”. Their invigorating struggle lasted about a decade, and ever since then, the code has lain at the foundation of biological understanding — and misunderstanding.
The aim of the decoding effort was to learn how the “letters” of a DNA sequence mapped to the amino acid sequence of the cognate protein. As it turned out, the solution was rather disappointing, as most scientists saw it. Having anticipated the most elegant bit of computer-like programming imaginable, they found a genetic code they could only term “redundant” or “degenerate” because of its apparent inefficiency. It was as if the dots and dashes of the Morse code mapped to the English alphabet, not one-to-one, but rather with individual English letters corresponding to several different dot-dash patterns.
In the case of the genetic code, 61 different three-letter sequences, or codons, mapped to only 20 amino acids. with as many as six codons representing a single amino acid. This, as the scientists’ thinking went, required an entirely superfluous cellular “machinery” to deal with all the redundant codons. How could natural selection come up with such a fudged and wasteful arrangement?
(Such was the thinking at the time. In recent years, thanks to the challenge from intelligent design proponents, many biologists have decided that we should expect inefficiency from nature. They delight in seeing wastefulness (junk DNA!) wherever possible — all the better to charge the Intelligent Designer with being hopelessly incompetent. Unfortunately, as junk DNA goes the way of phlogiston and light-transmitting ether, these particular biologists are the ones being exposed for incompetence1. As for intelligent design, readers will understand that I don’t belong in that camp either.)
A great deal has happened in the past decades to paint the picture in new and more vivid colors. Biologists are, slowly but surely, getting over the code delusion. In Look What’s Happened to Genetic Synonyms! I consider the matter from the standpoint of code efficiency — and ask whether we can reasonably speak of a code at all, at least in the sense that computer scientists speak of it.
Synonymous codons, we now know, can make huge differences. They play major roles in the regulation of gene expression and in shaping the functions of the proteins they have a hand in generating. To pursue our rough analogy: imagine again that you have a “redundant” Morse code, and that you are looking at a particular set of dot-dash patterns representing the successive letters of an English sentence. Then you begin substituting synonymous coding elements for existing ones. Since the encoding of English letters remains unchanged, you might expect no differences in the message. But you find to your surprise that some of the synonymous substitutions, or groups of substitutions, result in an unexpected word being added to the sentence, or in some of the words disappearing, or in phrases of the sentence exchanging place, or in the entire sentence being dropped from the larger transmission2.
In such a situation, you could not say that the synonymous Morse code elements were really synonymous. They would remain equivalent in a narrow sense — synonymous dot-dash patterns would still represent the same English letter — but it would also happen that a great deal was going on beside that reliable correspondence. Moreover, we need to imagine, not that these additional changes ruin the text, but rather that, in order for the proper and intended meaning to be achieved, the changes are essential.
Think of it this way. If you were a Morse code telegrapher using our “inefficient” version of the code, you would have to possess an as yet inconceivable understanding of the way whole messages are formed and transformed before you could send the desired text. And if you possessed that wisdom, you would in fact be able to communicate with a richness of meaning far outstripping anything you could manage with the most perfectly “efficient” and unexceptionable digital code. Such is the wisdom that seems innate to the cell and organism.
All this gives you a pretty good idea how synonymous codons work in the organism — except that, even in the narrow sense, a codon of the genetic code does not always represent the same amino acid in whatever protein might eventuate from the code. And bear in mind that the entire topic of synonymous codons has been a rather remote by-way in genetic studies. There are an overwhelming number of other, non-code-like factors bearing on what the organism makes of any particular genetic sequence.
The recent work on synonymous codons reminds us of themes now being sounded in virtually every field of molecular biology. In the first place, we learn that even what has been construed as the most code-like aspect of the organism — namely, its DNA and RNA sequence — is far from being a code in any strict sense. The sequence does not have an unambiguous, univocal, one-dimensional, digital sort of significance, but speaks with the many-layered richness of gestural communication. The use of synonymous codons is also context-dependent; the meaning of any given codon depends on what else is going on in its surroundings. Further, we see here the same multi-functionality we seem to find everywhere we look in the organism. Nothing serves just one function, but rather is connected to many interwoven processes — some of them, to immediate appearances, so highly disparate that one naturally wonders, “How can they be so intimately woven together?”
The challenge for biologists today is to find a way of thinking about the organism adequate to the many overlaid and simultaneous “voices” with which it speaks in all its details. And the barrier impeding biological progress is the habit of seeking the kind of single-arrow causal explanation imagined (falsely) to be characteristic of the physical sciences.
But you can read much more in “Look What’s Happened to Genetic Synonyms!”
1. Not so long ago I sat in disbelief as I watched a video of P. Z. Myers — often cited as the most prominent blogger among professional biologists — lecturing to a convention of atheists in November, 2011. He was using a hundred-foot rope to illustrate the high percentage of a gene that is supposedly useless junk. I couldn’t help wondering: has this guy completely lost contact with the literature of genetics, gene regulation, and chromosome dynamics? Myers would do well to browse through the collection of notes, How the Organism Decides What to Make of Its Genes. Much of that document bears on the question of junk DNA.
2. For those aware of the technical details: the analogy is to post-translational modifications of a protein, alternative splicing of an mRNA, differential folding of a protein, and translational repression or degradation of an mRNA. All these can be affected differently by different synonymous codons.
The difference between physical and biological explanation is treated in From Physical Causes to Organisms of Meaning.
For a more realistic picture of the countless factors playing a role in gene expression, skim through the collection of notes I’ve called How the Organism Decides What to Make of Its Genes.
This document: https://bwo.life/org/comm/ar/2013/genetic-synonyms-are-not-synonymous_12.htm
Steve Talbott :: Why Genetic Synonyms Are Not Synonymous