Theory of Intelligent Design, the best explanation of Origins

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The second code of DNA

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1 The second code of DNA on Sun Sep 27, 2015 3:46 am


Codes Within Codes: How Dual-Use Codons Challenge Statistical Methods for Inferring Natural Selection

The argument of the double function of the genetic code
 1. An “overlapping language” has been found in the genetic code, according to HealthDay News at MedLine Plus from the National Institutes of Health (NIH).
2. One language describes how proteins are made, and the other helps direct genetic activity in cells. One language is written on top of the other, which is why this other language went undiscovered for so long, according to the report in the 2013 Dec. 13 issue of Science.
3. The original paper by Stergachis et al. writes  about “evolutionary constraints” of the overlapping codes. They wrote: “Our results indicate that simultaneous encoding of amino acid and regulatory information within exons is a major functional feature of complex genomes. The information architecture of the received genetic code is optimized for superimposition of additional information, and this intrinsic flexibility has been extensively exploited by natural selection. Although TF [transcription factor] binding within exons may serve multiple functional roles, our analyses above is agnostic to these roles, which may be complex.”
4. According to the research, natural selection constrains or eliminates change (purifying selection) is not helpful for creating new organs or functions. 
5. Thus, for Darwinists to explain unguided physical processes is already impossible and with this new discovery they are even in bigger trouble.
6. The words: information, architecture, optimized, and function are always and only referring to a person with thinking feeling and willing. Other proposed agents cannot on their own give information, design, optimize or execute tasks. This has never been shown.
7. Such an intelligently designed complex genetic code with double or even triple functions could have been created only by God, the Supreme Designer.
8. God exists.

David Klinghoffer recently noted the discovery of dual-use codons, dubbed "duons," where a triplet of nucleotides can have multiple functions. Of course one of those is the standard function of encoding an amino acid. But now it turns out a codon can have another function as well: it can bind transcription factors which regulate the transcription of the gene. As many are now observing, this means that a single nucleotide sequence can have multiple levels of meaning. That is to say, there are multiple codes within the genetic code. In fact, one commentator observed that on the same analysis, codons may have more than two uses:

By this logic one could coin the term "trion" by pointing out that histone binding is also independently affected by A-C-T-G letter frequencies within protein-coding stretches of DNA.
But this isn't the first time that scientists have discovered multiple codes in biology. Earlier this year I discussed research that found an analog code in the DNA that helps regulate gene expression, in addition to the digital code that encodes primary protein sequence. In other cases, multiple proteins are encoded by the same gene! And then of course there's the splicing code, which helps control how RNAs transcribed from genes are spliced together in different ways to construct different proteins (see here and here).
It boggles the mind to think about how such "codes within codes" could evolve by random mutation and natural selection. But now it turns out that evidence of different functions for synonymous codons could threaten many standard methods used to infer selection in the first place

Because of redundancy in the genetic code, there are anywhere between two and six codons that will encode any given amino acid that life uses. These are called "synonymous codons" because they all have the same standard function in the genetic code: encoding the same amino acid. But this new study shows that codons can have other functions as well -- like binding transcription factors. The paper concludes:

Our results indicate that simultaneous encoding of amino acid and regulatory information within exons is a major functional feature of complex genomes. The information architecture of the received genetic code is optimized for superimposition of additional information and this intrinsic flexibility has been extensively exploited by natural selection. Although TF [transcription factor] binding within exons may serve multiple functional roles, our analyses above is agnostic to these roles, which may be complex.
(Stergachis et al., "Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution," Science, Vol. 342: 1367-1372 (December 13, 2013).)
Of course "exploited by natural selection" is another way of saying "these codons are rife with different types of potentially useful functions." A news article in Science elaborates on the findings:
Despite redundancy in the genetic code, the choice of codons used is highly biased in some proteins, suggesting that additional constraints operate in certain protein-coding regions of the genome. ... The authors determined that ~14% of the codons within 86.9% of human genes are occupied by transcription factors. Such regions, called "duons," therefore encode two types of information: one that is interpreted by the genetic code to make proteins and the other, by the transcription factor-binding regulatory code to influence gene expression. This requirement for transcription factors to bind within protein-coding regions of the genome has led to a considerable bias in codon usage and choice of amino acids, in a manner that is constrained by the binding motif of each transcription factor.
The paper argues that because there's often a bias towards certain synonymous codons over other synonymous codons, this shows a "code" where transcription factors can "prefer" to bind to certain codons during processes that regulate gene expression. Because they haven't elucidated the exact workings of this "code," it's hard to say for sure whether codon biases result from an actual "code," or just preferences of the binding motifs of transcription factors. To understand how exactly these mechanisms work, more work will need to be done.
Nonetheless, one thing is clear: there ARE biases towards certain synonymous codons, meaning synonymous codons have some function, meaning synonymous codons are NOT functionally neutral. Given that we know that synonymous codons can preferentially bind transcription factors (or other molecules, like histones), we have a good idea of what kinds of functional mechanisms are causing certain synonymous codons to be preferred.

All of this poses a major conundrum for statistical methods that evolutionists use to infer natural selection in studies purporting to explain the evolution of genes. Last summer here on ENV, I discussed and critiqued such statistical methods. According to this way of thinking, an excess of nonsynonymous mutations implies "positive selection" is preserving mutations that change amino acid sequence. An excess of synonymous mutations implies selection is at work to "weed out" mutations that change amino acid sequence -- i.e., there is no "positive selection." If synonymous and nonsynonymous mutations are fixed at a proportional rate, this indicates no selection pressure, and the gene is undergoing "neutral" evolution.

To use these statistical techniques, evolutionary biologists rely on the crucial assumptions that (1) synonymous mutations are selectively neutral because they don't modify amino acid sequence in a protein or perform any other selectable functions, and (2) nonsynonymous mutations which change the amino acid sequence are preserved because they cause some selectable change in protein function. In my article last summer I cited multiple studies that challenge both assumptions. For example, the first assumption is challenged by a paper in Science which said the "discovery that synonymous codon changes can so profoundly change the role of a protein adds a new level of complexity to how we interpret the genetic code."[***] In other words, synonymous codons can have functions in addition to encoding an amino acid. This recent study in Science, however, provides additional strong evidence refuting the first assumption that synonymous mutations are selectively neutral.

(Indeed, the news article in Science also challenged the second assumption, stating, "Intriguingly, a large fraction of the variants that result in a nonsynonymous change are predicted not to alter protein function.")

But the main point of this new study is as follows: particular synonymous codons can be preferred for functional reasons. This means synonymous codons can have important functions in addition to encoding an amino acid, suggesting that the numerous studies which have purported to detect natural selection in genes, operating under the assumption that synonymous codons are selectively neutral, should be viewed with extreme skepticism.

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2 Duons: Parallel Gene Code Defies Evolution on Tue Nov 24, 2015 1:27 pm


Duons: Parallel Gene Code Defies Evolution 1

Researchers have just characterized a new, previously hidden genetic code embedded within the same sections of genes that code for proteins—utterly defying all naturalistic explanations for its existence.1
In addition to supplying many different types of genetic code that regulate function, the genome also provides highly complex coded templates for making a wide diversity of functional RNA molecules and proteins.

Protein-coding genes—those containing the key information to make proteins—hold the most-studied type of genetic code. Some of the most important chunks of code in genes are the exons, which specify the actual template for protein sequences.

In exons, three consecutive DNA letters form what is called a codon, and each codon corresponds to a specific amino acid in a protein. Long sets of codons in genes contain the protein-making information that ends up being translated into entire proteins that may be hundreds of amino acids in length.
Before this study, scientists were aware that the protein-coding regions of genes had mysterious signals other than codons that told the cell machinery how to regulate and process the RNA transcripts (copies of genes) prior to making the protein. Researchers originally thought that these regulatory codes and the protein template codes containing the codons operated independently of each other.
In reality, the new results showed that these codes actually work both separately and together. While one set of codons specifies the order of amino acids for a protein, the very same sequence of DNA letters also specifies where necessary cellular machinery (transcription factors) are to bind to the gene to make the RNA transcript that codes for a protein. As a result of this new discovery, these dual-function code sites in exons have been labeled “duons.” Scientists just last year reported that transcription factors clamped onto some exons inside genes but did not understand this dual code system until now.2
The human mind struggles to comprehend the overall complexity of the genetic code—especially the emerging evidence showing that some genes have sections that can be read both forward and backward.3Some genes overlap parts of other genes in the genome, and now it has been revealed that many genes have areas that contain dual codes within the very same sequence.1,4
Even the most advanced computer programmers can’t come close to matching the genetic code’s incredible information density and bewildering complexity. An all-powerful Creator appears to be the only explanation for this astounding amount of seemingly infinite bioengineering in the genome.


[1]Stergachis, A. B. et al. 2013. Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution. Science. 342 (6164): 1367-1372.

[2]Neph, S. et al. 2012. An expansive human regulatory lexicon encoded in transcription factor footprints. Nature. 489 (7414): 83-90.

[3]Tomkins, J. Bewildering Pseudogene Functions Both Forwards and Backwards. Creation Science Update. Posted on June 14, 2013, accessed December 19, 2013.

[4]Sanna, C. R., W. H. Li, and L. Zhang. 2008. Overlapping genes in the human and mouse genomes. BMC Genomics. 9: 169.

*Dr. Tomkins is Research Associate at the Institute for Creation Research and received his Ph.D. in genetics from Clemson University.

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