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Paper Finds Functional Reasons For "Redundant" Codons, Fulfilling a Prediction from Intelligent Design

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A new peer-reviewed paper in the journal Frontiers in Genetics, "Redundancy of the genetic code enables translational pausing," finds that so-called "redundant" codons may actually serve important functions in the genome. Redundant (also called "degenerate") codons are those triplets of nucleotides that encode the same amino acid. For example, in the genetic code, the codons GGU, GGC, GGA, and GGG all encode the amino acid glycine. While it has been shown (see here) that such redundancy is actually optimized to minimize the impact of mutations resulting in amino acid changes, it is generally assumed that synonymous codons are functionally equivalent. They just encode the same amino acid, and that's it.

Well, think again. The theory of intelligent design predicts that living organisms will be rich in information, and thus it encourages us to seek out new sources of functionally important information in the genome. This new paper fulfills an ID prediction by finding that synonymous codons can lead to different rates of translation that can ultimately impact protein folding and function.

This means that DNA contains multiple languages or encoded commands occupying the same string of contiguous bases. On the one hand, a string of nucleotide bases encodes amino acids. On the other hand, that same string contains information about the rate at which the ribosome should translate the protein so that it can properly fold into the right shape. The paper calls this "translational pausing." The ribosome is capable of reading both sets of commands -- as they put it, "[t]he ribosome can be thought of as an autonomous functional processor of data that it sees at its input." To put it another way, the genetic code is "multidimensional," a code within a code. This multidimensional nature exceeds the complexity of computer codes generated by humans, which lack the kind of redundancy of the genetic code. As the abstract states:

The codon redundancy ("degeneracy") found in protein-coding regions of mRNA also prescribes Translational Pausing (TP). When coupled with the appropriate interpreters, multiple meanings and functions are programmed into the same sequence of configurable switch-settings. This additional layer of Ontological Prescriptive Information (PIo) purposely slows or speeds up the translation decoding process within the ribosome. Variable translation rates help prescribe functional folding of the nascent protein. Redundancy of the codon to amino acid mapping, therefore, is anything but superfluous or degenerate. Redundancy programming allows for simultaneous dual prescriptions of TP and amino acid assignments without cross-talk. This allows both functions to be coincident and realizable. We will demonstrate that the TP schema is a bona fide rule-based code, conforming to logical code-like properties. Second, we will demonstrate that this TP code is programmed into the supposedly degenerate redundancy of the codon table. We will show that algorithmic processes play a dominant role in the realization of this multi-dimensional code.
They write that the ribosome's ability to undergo translational pausing "reveal[s] the ribosome, among other things, to be not only a machine, but an independent computer-mediated manufacturing system." The paper even suggests, "Cause-and-effect physical determinism...cannot account for the programming of sequence-dependent biofunction."

Apart from ID's expectation of finding new layers of information in the genome, the paper implicitly challenges some common evolutionary assumptions. The notion that shared synonymous codons are functionally irrelevant has been used to buttress arguments for Darwinian evolution.

For one thing, some evolutionists claim that phylogenetic signals can be carried by the distribution of synonymous codons since they're functionally equivalent. This paper suggests otherwise.

For another, seeking to infer the activity of natural selection, evolutionary biologists statistically analyze the frequency of synonymous (thought to be functionally unimportant) and nonsynonymous (thought to be functionally important) codons in a gene. (We've discussed this previously here and here.) As the thinking goes, if synonymous codons are functionally unimportant, then three conclusions may follow: a bias toward synonymous codons implies purifying selection in the gene, a bias towards nonsynonymous codons implies positive selection, and an equal balance implies neutral evolution (no selection). But if synonymous codons can have important functional meaning, then the whole methodology goes out the window, and hundreds of studies that used these methods to infer "selection" during the supposed "evolution of genes" could be wrong.

The evidence supports the view that synonymous codons have divergent effects upon translation, as the paper finds: "Data shows that with fixed levels of tRNA's, synonymously encoded mRNA's translate with different speeds" and "Recent work has built on the above observations showing a strong relationship between specific arrangements of codons in mRNA to the rate of translation." Genetic modifications in the lab can even induce translational pausing:

"Pausingfunction" is caused by specific mRNA codon sequences rather than by tunnel-protein interactions to amino acid sequences. This contention is supported by data involving the substitution of rare codons with synonymous codons in E. coli. If the pausing effect was solely related to the amino acid chain sequence, then replacing codons with synonymous codons should still produce the same folded amino acid chain with the same translation speed. However, substitution of rare codons with synonymous codons did produce a change in speed and conformation changes.
These changes in translational speed can have phenotypic effects:
For example, a silent mutation in the human gene ABCB1 caused a conformational change to occur in the P-glycoprotein. This protein folded differently caused by a temporal change in translation affecting the timing of the folding process. ... Thus, the protein folding pathways are affected by changes in the coding regions of DNA" (internal citations removed).
In short, "redundant" codons are not necessarily redundant at all. As the paper puts it: "we show why the term "degeneracy" is completely inappropriate. The dual coding functionality of redundancy is anything but 'degenerate.' It represents, instead, far more sophistication, layers, and dimensions of formal prescription." In fact, this paper "defines new universal linguistic-like rules needed to identify and characterize codon mappings of TP events." The authors write:
The TP code exhibits distinct meaning in relation to mappings between codons and pausing units. The TP code also exhibits a syntax or grammar that obeys strict codon relationships that demonstrate language properties. Because of the redundancy of the genetic code, it could be argued that the TP language is a subset of the genetic language. The subspace of the TP language resides, and thus appears to have a dependency on, the primary genetic code. Within this subspace, however, we argue that the TP language is decoupled from and remains independent of the protein-coding language.
Their conclusion about the high-information capacity of the genetic code is striking:
Redundancy in the primary genetic code allows for additional independent codes. Coupled with the appropriate interpreters and algorithmic processors, multiple dimensions of meaning, and function can be instantiated into the same codon string. We have shown a secondary code superimposed upon the primary codonic prescription of amino acid sequence in proteins. Dual interpretations enable the assembly of the protein's primary structure while enabling additional folding controls via pausing of the translation process. TP provides for temporal control of the translation process allowing the nascent protein to fold appropriately as per its defined function. This duality in the coding function acts to reduce the redundancy in the genetic code when viewed holistically. The functionality of condonic redundancy denies the ill-advised label of "degeneracy." When simultaneously combined with other coding schemas such as intron/exon boundary conditions, and overlapping and oppositely oriented promoters, multiple dimensions of independent coding by the same codon string has become apparent.

In his 2001 book No Free Lunch, William Dembski explained the primary prediction of intelligent design:

[W]hat about the predictive power of intelligent design? Intelligent design offers one obvious prediction, namely, that nature should be chock-full of specified complexity and therefore should contain numerous pointers to design ... This prediction is increasingly being confirmed. (p. 362)
Multidimensional codes and new levels of specified complexity are exactly what ID predicts, and they're exactly what this paper is reporting. It's this sort of sophisticated, information-rich control that is expected by intelligent design, in contrast to Darwinian biology which fails to anticipate it. On the contrary, Darwinian advocates publish mountains of papers banking upon the unquestioned assumption that there is no important, functional reason for the existence of "redundant" or "degenerate" features. Slowly but surely, the data are turning the tide in the evolution debate.

Image source: ka2rina/Flickr.