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How Many Codes in Life?

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On a recent ID the Future podcast, Jonathan Wells listed six codes used by cells: the genetic code, the epigenetic code, the membrane code, the sugar code, the RNA splicing code, and the bioelectric code. Geoffrey North at Current Biology, on the other hand, contends that there is only one code, because all the others ultimately derive from DNA. Who’s right?

As each eager new candidate comes along, it is invariably dubbed a new second genetic code — never a third or fourth genetic code…. Why is this? In the contemporary parlance of the internet age, a kind of crowd-sourced opinion is being made, a thumbs down to the claim, which, if truly meaningful and useful, would surely be taken up into general usage, to become the second genetic code. I would suggest we accord the one, universal genetic code its deserved special place by not nominating others to join it in a list. [Italics in original, bold added.]

So is multiplying codes a taxonomic trick, a violation of Occam’s Razor? Lest we be accused of standing by our ID colleague regardless, let’s look at some other news about codes in living things and then reason about what makes a code a code.

Traffic Codes

A news item from UT Southwestern claims yet another code has been discovered in the cell. After describing the regular genetic code, the article gets to the point:

What researchers found was that not only does the sequence of the amino acids matter, but so does the speed of the process in which the amino acids are put together into a functional protein.

“Our results uncovered a new ‘code’ within the genetic code. We feel this is quite important, as the finding uncovers an important regulatory process that impacts all biology,” said Dr. Yi Liu, Professor of Physiology.

This discovery relates to the issue of synonymous and non-synonymous codons we reported earlier. There’s more to the claim, however. The researchers claim that the speed of translation affects how the protein will fold. This will affect its shape, and ultimately its function. So while a point mutation may change a nucleotide in a gene without altering the amino acid its codon produces, the resulting messenger RNA may be translated at a different speed. Consequently, the protein may fold differently and have a different function — or cause disease.

If this is a code, it rides on the genetic code. The triplet sequence will determine the amino acid used, but a different synonymous sequence will affect the protein that results. Conceivably one could say this is all one genetic code and leave it at that. But it’s a bit like Shakespeare’s use of a “play within a play” in Hamlet. The interior play could stand alone as entertainment, but it contributes to the larger play. The larger play, though, could have related the plot without it. (Note that each play contains separate and distinct information, although they both are spoken in English.) It seems fair, then, to describe the play-within-a-play as a distinct play. Shakespeare used the device to achieve a result more profound than either play could alone.

In addition to the “code” analogy, the press release uses a “highway” analogy with slow and fast lanes. We can use the same reasoning here. Think of the genetic code as monorail with a train that maxes out at one speed. You get on at one point, and end up at another point at a set time. Now consider a six-lane interstate highway in its place. Suddenly you have many more options that all lead to the same endpoint, but at different speeds. There’s also a new set of rules: “Carpools only” or “Slower traffic keep right.” All this additional information should qualify as a separate “code” from the “monorail code.”

Histone Code Update

The University of Copenhagen announces a new function for histones, the proteins that wrap DNA and control access to genes (this compares to Wells’s “epigenetic code”). They compare their discovery to revealing “undiscovered white dots on the map.” Sounds like more information has been found; let’s see.

The four core histones have so-called tails, and among other things they signal damage to the DNA and thus attract the proteins that help repair the damage. Between the histone “yarn balls” we find the fifth histone, Histone H1, but up until now its function has not been thoroughly examined.

Using a so-called mass spectrometer, a technique developed in collaboration with fellow researchers at the Novo Nordisk Foundation Centre for Protein Research, Niels Mailand and his team have discovered that, surprisingly, the H1 histone also helps summon repair proteins.

Scientists at the University of Barcelona, meanwhile, claim to be “Shaking up the fundamentals of epigenetics” — a bit of hyperbole, perhaps — by showing that chromatin marks do not always have the same effect on gene expression during development. From modENCODE data, they found that some genes in worms and fruit flies were highly expressed during development without the chromatin marks that the “accepted view” expects should have been there. This is a work in progress that possibly suggests deeper regulations than are currently understood.

A Pulse Code?

At Caltech, according to Now@Caltech, researchers found another layer of regulation in gene expression. “Cells Rhythmically Regulate Their Genes,” the headline reads. The scientists labeled some transcription factors with red and green glowing markers and watched them moving in the nucleus. What they found was another source of informational guidance in the combinatorial code of transcription factors. It’s a new time-based method of gene regulation that is “largely unexplored” —

Previously, researchers have thought that the relative concentrations of multiple transcription factors in the nucleus determine how they regulate a common gene target–a phenomenon known as combinatorial regulation. But the new study suggests that the relative timing of the pulses of transcription factors may be just as important as their concentration.

“Most genes in the cell are regulated by several transcription factors in a combinatorial fashion, as parts of a complex network,” says Cai. “What we’re now seeing is a new mode of regulation that controls the pulse timing of transcription factors, and this could be critical to understanding the combinatorial regulation in genetic networks.”

How Many Codes Again?

Some codes are not really codes. Pig Latin, for instance, is just a humorous corruption of English; Rot13 is just an encryption algorithm that outputs the same English words after rotating them 13 places in the English alphabet. But it seems fair to categorize codes separately if they contain unique information and produce unique results. Even if histones are built from DNA, once they are assembled, they no longer rely on the genetic code. They follow their own rules of tagging genes with “tails” made of other molecules. Transcription factors and their pulsations, similarly, act apart from the language of DNA triplet codons. How much more the sugar code, membrane code and bioelectric codes that are not even made up of amino acids?

It would be as ridiculous to lump all of these into a single genetic code as it would be to lump Morse Code into the genetic code on the grounds that the fingers of a telegraph operator contain proteins built from DNA. Codes are distinguished by the information they contain and the rules that they follow. As Jonathan Wells cogently argued in the podcast, there’s more information in life than can be explained by one genetic code. He identified “at least” six codes, never implying that the extent of coded information in life stops there.

Image: Telegraph operator, by Tropenmuseum, part of the National Museum of World Cultures [CC BY-SA 3.0], via Wikimedia Commons.

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