Friday, January 25, 2013

Here is That New Paper on Synonymous Nucleotides

Evolutionists Are Bailing Out

One of the most common tests evolutionists use, when studying how genes are supposed to have evolved, is to compare the non-synonymous and synonymous genetic differences. That is, if a gene that codes for a particular protein is found in several species, then evolutionists interpret differences in the gene, across those species, as the result of mutations in the evolutionary process. And while most mutations cause a change in the resulting protein amino acid sequence, some mutations do not affect the amino acid that is coded for. These two kinds of mutations are referred to as non-synonymous and synonymous, respectively, and their relative proportions are important to evolutionists. They believe that the while the non-synonymous mutations are important, because they change the resulting protein, the synonymous mutations on the other hand are not important. Therefore, if the ratio of the non-synonymous to synonymous mutations is high, then evolutionists think most of the mutations are important and so the gene is undergoing strong selection which is driving significant evolutionary change. But if the ratio of the non-synonymous to synonymous mutations is low, then evolutionists think most of the mutations are not important and so the gene is undergoing purifying selection which rejects most changes because the lower fitness. In that case the synonymous mutations occur merely because they don’t change the protein. As you can see this entire approach is deeply wedded to evolutionary assumptions and its main result is an inference about how genes evolved. If evolution is true then that is useful information, but if not then the entire exercise is a waste. Well for several years evidence has been growing that this approach and its results do, in fact, have much less meaning than evolutionists believe and, as we discussed here, there is a much better way.

Very simply put, the problem with comparing non-synonymous to synonymous differences between genes is that synonymous differences are not unimportant as evolutionists have assumed. As we have discussed protein coding genes carry a multitude of signals and the resulting protein amino acid sequence is just one of many layers of information in the gene sequence. And for most of these signals, what are synonymous differences in the protein sequence are most definitely not synonymous in the message the signal sends.

All of this is highlighted in a new survey paper on messenger RNA, the copy of the DNA gene. As the paper explains:

There are several well-documented ways in which synonymous sites exert their impact on gene functions: effect on mRNA splicing, mRNA folding, stability and regulation of translation through utilization of preferred synonymous codons that translate more efficiently and accurately. Additional and sometimes opposing selective forces appear to affect codon frequency as well. Previous findings show roles for synonymous positions in RNA–RNA interactions, which influence the translation efficiency, and in RNA–RNA cross-talk, which is a key to biological regulation of expression and transcriptome complexity. Emerging evidence shows that “silent” substitutions carry a wealth of information, which is written over the encoded amino acid sequence, and that this information can be used to regulate translation speed, protein homeostasis, metabolic fate and even posttranslational modifications, which will be discussed in this review. Here we will focus on the RNA level of regulation and the role of synonymous sites and mRNA structure in generating biological complexity.

Once again evolutionary assumptions are being proven wrong by science. The facts of molecular biology make no sense on evolution, yet untold numbers of evolutionary studies, incorporating this test of the ratio of non-synonymous to synonymous mutations, are beholden to evolutionary assumptions.

20 comments:

  1. Besides falsifying evolutionary presuppositions about synonymous mutations, there is another finding in this paper that places further constraint on neo-Darwinian evolution:

    Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity. – Jan 2013
    Excerpt: Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides.,,,
    Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles.
    http://www.ncbi.nlm.nih.gov/pubmed/23293005

    As well, besides multifunctionality being found for synonymous positions, it is now found, by ENCODE, that the majority of protein coding regions are ‘overlapping’ with one another:

    Time to Redefine the Concept of a Gene? – Sept. 10, 2012
    Excerpt: As detailed in my second post on alternative splicing, there is one human gene that codes for 576 different proteins, and there is one fruit fly gene that codes for 38,016 different proteins!
    While the fact that a single gene can code for so many proteins is truly astounding, we didn’t really know how prevalent alternative splicing is. Are there only a few genes that participate in it, or do most genes engage in it? The ENCODE data presented in reference 2 indicates that at least 75% of all genes participate in alternative splicing. They also indicate that the number of different proteins each gene makes varies significantly, with most genes producing somewhere between 2 and 25.
    http://networkedblogs.com/BYdo8

    It is readily apparent that this ‘overlapping multifunctionality’ places severe constraint on Darwinian evolution:

    If we were to actually get a proper ‘beneficial mutation’ in a ‘overlapping multifunctional’ gene we would be encountering something akin to this illustration found on page 141 of the book “Genetic Entropy” by Dr. Sanford.

    S A T O R
    A R E P O
    T E N E T
    O P E R A
    R O T A S

    Which is translated ;
    THE SOWER NAMED AREPO HOLDS THE WORKING OF THE WHEELS.
    This ancient puzzle, which dates back to 79 AD, reads the same four different ways. Thus, if we change (randomly mutate) any single letter we may get a new meaning for a single reading read any one way but we will consistently destroy the other 3 readings (functions) of the message with the new mutation (save for the center letter).
    For Darwinist to continue to believe in ‘random’ mutations to generate the staggering level of ‘overlapping multifunctionality’ we find in life is absurd in the highest order!

    As to Theistic Evolutionists(TEs), who believe God guides evolution in a ‘bottom up’ fashion, (apparently in a way that is undetectable to humans), all I ask TEs to consider is do you think that it would be easier for God to incrementally change a ‘overlapping multifunctional’ gene of any organism in a bottom up manner or do you think it would be easier for Him to design each kind of organism in a top down manner? Especially considering the fact that many genes are usually associated for any given phenotypic trait?

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    1. Notes:

      “Whatever we may try to do within a given species, we soon reach limits which we cannot break through. A wall exists on every side of each species. That wall is the DNA coding, which permits wide variety within it (within the gene pool, or the genotype of a species)-but no exit through that wall. Darwin’s gradualism is bounded by internal constraints, beyond which selection is useless.”
      R. Milner, Encyclopedia of Evolution (1990)

      Epistasis between Beneficial Mutations - July 2011
      Excerpt: We explored epistasis for beneficial mutations by constructing genotypes with pairs of mutations that had been previously identified as beneficial to the ssDNA bacteriophage ID11 and by measuring the effects of these mutations alone and in combination. We constructed 18 of the 36 possible double mutants for the nine available beneficial mutations. We found that epistatic interactions between beneficial mutations were all antagonistic—the effects of the double mutations were less than the sums of the effects of their component single mutations. We found a number of cases of decompensatory interactions, an extreme form of antagonistic epistasis in which the second mutation is actually deleterious in the presence of the first. In the vast majority of cases, recombination uniting two beneficial mutations into the same genome would not be favored by selection, as the recombinant could not outcompete its constituent single mutations.
      http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002075

      Mutations : when benefits level off - June 2011 - (Lenski's e-coli after 50,000 generations)
      Excerpt: After having identified the first five beneficial mutations combined successively and spontaneously in the bacterial population, the scientists generated, from the ancestral bacterial strain, 32 mutant strains exhibiting all of the possible combinations of each of these five mutations. They then noted that the benefit linked to the simultaneous presence of five mutations was less than the sum of the individual benefits conferred by each mutation individually.
      http://www2.cnrs.fr/en/1867.htm?theme1=7

      Testing Evolution in the Lab With Biologic Institute's Ann Gauger - podcast with link to peer-reviewed paper
      Excerpt: Dr. Gauger experimentally tested two-step adaptive paths that should have been within easy reach for bacterial populations. Listen in and learn what Dr. Gauger was surprised to find as she discusses the implications of these experiments for Darwinian evolution. Dr. Gauger's paper, "Reductive Evolution Can Prevent Populations from Taking Simple Adaptive Paths to High Fitness,".
      http://intelligentdesign.podomatic.com/entry/2010-05-10T15_24_13-07_00

      Response from Ralph Seelke to David Hillis Regarding Testimony on Bacterial Evolution Before Texas State Board of Education, January 21, 2009
      Excerpt: He has done excellent work showing the capabilities of evolution when it can take one step at a time. I have used a different approach to show the difficulties that evolution encounters when it must take two steps at a time. So while similar, our work has important differences, and Dr. Bull’s research has not contradicted or refuted my own.
      http://www.discovery.org/a/9951

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    2. Moreover, it should be noted that,,,

      Time to Redefine the Concept of a Gene? – Sept. 10, 2012
      Excerpt: Based on these results, it seems clear that the RNA transcripts are the real carriers of genetic information. This is why some members of the ENCODE team are arguing that an RNA transcript, not a gene, should be considered the fundamental unit of inheritance.
      http://networkedblogs.com/BYdo8

      Yet, as radical as that ‘redefinition to the RNA transcript,’ of the fundamental unit of inheritance would be to undermining the entire edifice of the modern synthesis upon which neo-Darwinism is built (genetic reductionism), the fact of the matter is, as much as I would love to see that undermining happen, that these current findings present us with yet another irreducibly complex situation in that ANY changes to DNA nucleotides, as Dr. Hunter has pointed out, effect RNA in a multifunctional way, yet, on the other hand, the RNA is regulating the gene in a multifunctional way.,,, Needless to say, this puts neo-Darwinists, once again, between the proverbial ‘rock and a hard place’!,,,
      Perhaps, after getting beat to a pulp with the rock of empirical evidence time after time, it is time for Darwinists to choose to ‘work with with the rock’ instead of choosing to get repeatedly beat to a pulp with it?

      Music, verse and video:

      5th service band Featuring TRU-SERVA – Solid Rock
      http://www.youtube.com/watch?v=G4jD70Y-mQ0

      Matthew 7:24
      “Therefore everyone who hears these words of Mine and acts on them, may be compared to a wise man who built his house on the rock.

      But to the unwise???,,, well perhaps this cartoon will help get the point across,,,

      Wile E. Coyote – cartoon video
      http://www.youtube.com/watch?v=hz65AOjabtM

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    3. Supplemental notes:

      A genome-wide study of dual coding regions in human alternatively spliced genes. - 2006
      Excerpt: Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcripts and show that approximately 7% of alternatively spliced genes contain dual (multiple) coding regions.
      http://www.ncbi.nlm.nih.gov/pubmed/16365380

      Dual-Coding Genes in Mammalian Genomes - 2007
      Excerpt: A textbook human gene encodes a protein using a single reading frame. Alternative splicing brings some variation to that picture, but the notion of a single reading frame remains. Although this is true for most of our genes, there are exceptions. Like viral counterparts, some eukaryotic genes produce structurally unrelated proteins from overlapping reading frames. The examples are spectacular (G-protein alpha subunit [Gnas1] or INK4a tumor suppressor), but scarce. The scarcity is anthropogenic in origin: we simply do not believe that dual-coding genes can occur in eukaryotes. To challenge this assumption, we performed the first genome-wide scan for mammalian genes containing alternative reading frames located out of frame relative to the annotated protein-coding region. Using a newly developed statistical framework, we identified 40 such genes. Because our approach is very conservative, this number is likely a significant underestimate, and future studies will identify more alternative reading frame–containing genes with fascinating biology.
      http://www.plosone.org/article/info:doi/10.1371/journal.pcbi.0030091

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  2. You really should be careful with publishing this sort of work, CH. You know it tends to trigger a quote-dump spasm from BA77.

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  3. While ago we already talked,
    About multi dimensional encoding
    So I must say these articles linked above help
    Understanding how secondary messages are
    Placed into a linear sequence.
    !

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  4. The paper indicates that the selective constraints on synonymous substitution are not as simplistic as might be thought - they are not invariably neutral and bias-free. That things are sometimes neutral and sometimes not is hardly a surprise. Who determined that substitution is subject to systematic biases? CH? Of course not. It was those darned evolutionists. You can hardly use a paper based upon evolutionary assumptions to invalidate evolutionary assumptions.

    Ooh look - Wikipedia on 'Ka/Ks ratio has a section on 'Complications'. And another on 'Limitations'.

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    1. You can hardly use a paper based upon evolutionary assumptions to invalidate evolutionary assumptions.

      If evolutionary assumptions lead to more and more false predictions and increased theory complexity, then it casts doubt on the theory. There is no scientific evidence that genomes spontaneously arise, not to mention the incredible layers of information contained within genes.

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    2. What falsified predictions did you have in mind?

      As for theory complexity, adjusting a theory to conform to new data is good scientific practice. Only with religious dogma is inflexibility held, by some, to be a virtue.

      No, we do not know how the genome arose but that is all we can say, we don't know. It's a perfectly respectable scientific response when you actually don't know. It does not mean that therefore some intelligent agent must have been responsible.

      And treating information as a property of the genome is, in my view, misleading at best. It is akin to saying that redness is a property of a red car when the better explanation, in fact, is that it is how the particular wavelengths of light reflected by the car are represented in our mental image of that car. The suspicion is that the use of an ill-defined notion of "information" plays off the popular usage which, as we know, implies a sender as well as a receiver and purpose.

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    3. It's a perfectly respectable scientific response when you actually don't know.

      And is it then "a perfectly respectable scientific response" to insist it is a fact?

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    4. Cornelius Hunter

      And is it then "a perfectly respectable scientific response" to insist it is a fact?


      Is it a perfectly respectable scientific response to continually lie and equivocate between the observed fact of evolution and the theory of evolution that explains the observed fact?

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    5. thorton- all YOU ever do is equivocate- you equivocate between the observed fact of evolution- things change- and evolutionism. That is your entire "argument"-> equivocation.

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  5. BA
    As to Theistic Evolutionists(TEs), who believe God guides evolution in a ‘bottom up’ fashion, (apparently in a way that is undetectable to humans), all I ask TEs to consider is do you think that it would be easier for God to incrementally change a ‘overlapping multifunctional’ gene of any organism in a bottom up manner or do you think it would be easier for Him to design each kind of organism in a top down manner? Especially considering the fact that many genes are usually associated for any given phenotypic trait


    How does "easier" makes sense in terms of an omnipotent being? Is there some theological reason God must follow a topdown method? Are you saying God is incapable of creating a system of bottom up? Does God require genes to create a phenotype?

    Once you create an unbounded designer you can explain everything, and and explain nothing specifically

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  6. V: Once you create an unbounded designer you can explain everything, and and explain nothing specifically

    J: Theists that posit a designer to account for the FIT of the natural human mode of inductive inference to real caused event regularities (per atheism, deism, etc, that FIT need not even exist), etc can't contend that "everything" is possible. Indeed, once theodicy is shown to be impossible for an inferred world with event regularities discoverable by applying inductive criteria, that species of ID is falsified (contradicted). Unfortunately, short of such an approach, it's impossible to "falsify" (even by parsimony criteria, etc) much of anything for the reasons like that articulated by Sir Martin Rees that I posted to you earlier.

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  7. Jeff January 26, 2013 at 3:26 PM

    [...]

    J: Theists that posit a designer to account for the FIT of the natural human mode of inductive inference to real caused event regularities (per atheism, deism, etc, that FIT need not even exist), etc can't contend that "everything" is possible.


    If the posited designer is held to be unbounded, like the Christian God, then by definition it would be capable of anything possible.

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  8. There's two senses of "possible" for a free-agent. There's that which one COULD do if he/she was so motivated, then there's that which can possibly motivate. The latter is the reason why some theists say God can't choose to be other than sympathetic, etc. They are positing that God simply has no such NATURAL motivation to CHOOSE from.

    The former is acknowledged in court cases. We all COULD murder in the former sense. But apart from actions that are more parsimoniously explained by the motive of murder, one doesn't infer the existence of the motive itself.

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    1. Jeff ,

      There's two senses of "possible" for a free-agent. There's that which one COULD do if he/she was so motivated, then there's that which can possibly motivate


      With an purposely unknown designer, nothing can be said but he is capable of design, his motivation or his abilities can only be assumed from the set of all designers if that can even be known..


      . The latter is the reason why some theists say God can't choose to be other than sympathetic, etc. They are positing that God simply has no such NATURAL motivation to CHOOSE from.


      Some theists might say it is not that a god is not motivated , it is that God cannot do what is not in his nature,it is logically impossible. Now of course there is a lot of wiggle room available, an omnipotent know all. So what can seem bad,ordering children to be chopped to pieces, to a limited being can actually be seem as part of the plan of ultimate good, for the best.

      Indeed, once theodicy is shown to be impossible for an inferred world with event regularities discoverable by applying inductive criteria, that species of ID is falsified (contradicted

      My point is that it is with an unknown designer with unknown abilities nothing logically possible can be shown to be impossible . Would have an example of something impossible?

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  9. Correction:

    J1: But apart from actions that are more parsimoniously explained by the motive of murder, one doesn't infer the existence of the motive itself.

    J2: But apart from actions that are more parsimoniously (or, alternatively, less ad-hoc-ly) explained by the motive of murder, one doesn't infer the existence of the motive itself.

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  10. So, an allegedly unlimited designer-god has limits when it's convenient to your assertions.

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