Intelligent Design

This is embarrassing: “Darwin’s Doubt” debunker is 14 years behind the times

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Over at The Skeptical Zone, Mikkel “Rumraket” Rasmussen has written a post critical of Dr. Stephen Meyer, titled, Beating a dead horse (Darwin’s Doubt), which is basically a rehash of comments he made on a thread on Larry Moran’s Sandwalk blog last year. The author’s aim is to expose Dr. Stephen Meyer’s “extremely shoddy scholarship,” but as we’ll see, Rasmussen’s own research skills leave a lot to be desired.

Did Dr. Meyer fail to document his sources?

Rasmussen focuses his attack on chapter 10 of Dr. Meyer’s book, “Darwin’s Doubt.” He writes:

Having read the book, a recurring phenomenon is that Meyer time and again makes claims without providing any references for them. Take for instance the claim that the Cambrian explosion requires lots of new protein folds, from Chapter 10 The Origin of Genes and Proteins:

(Rasmussen proceeds to quote from Meyer’s book, on which he comments below – VJT.)

In the whole section Meyer dedicates to the origin of novel folds, he makes zero references that actually substantiate [his assertion] that the [C]ambrian diversification, or indeed any kind of speciation, or the [appearance of] new cells types or organs, require[d] new protein folds. ZERO. Not one single reference that supports these claims. At first it reads like what I quote[d] above, lots of claims, no references. Later on he eventually cites the work of Douglas Axe that atte[m]pts to address how hard it is to evolve new folds (and that work has its own set of problems, but never mind that). Axe makes the same claim in his ID-journal Bio-complexity papers (which eventually Meyers cites), but in Axe’s papers, that claim is not supported by any reference either. It’s simply asserted as fact. In other words, Meyer makes a claim, then cites Axe making the same claim. Neither of them give a reference.

(N.B. For ease of readability, I have used square brackets to correct Rasmussen’s spelling and punctuation errors, and I have also inserted four extra words, without which his meaning would have been obscure to readers, in the preceding paragraph – VJT.)

Rasmussen repeats his accusation that Dr. Meyer frequently makes claims in his book without providing any references for them, at the very end of his post:

Later Meyer gets a ID-complexitygasm when he asserts, again without any support, that:

“The Cambrian animals exhibit structures that would have required many new types of cells, each requiring many novel proteins to perform their specialized functions. But new cell types require not just one or two new proteins, but coordinated systems of proteins to perform their distinctive cellular functions.”

Where does he get this? His ass, that’s where.

Do new cell types require new kinds of proteins?

I find it quite astonishing that Rasmussen would require documentation for Dr. Meyer’s claim that new cell types would require new types of proteins, for three reasons. First, it’s a well-known fact that each different cell type has different cluster of differentiation proteins. Bojidar Kojouharov, a Ph.D. Student in Cancer Immunology, describes these proteins as follows:

Clusters of Differentiation (CD) are cell surface proteins used to differentiate one cell type from another. Each CD marker is a different surface protein from the others. As such, it will likely have different functions and may be expressed on different cells. Technically, different CD markers don’t really have to have anything in common, other than the fact that they are on the cell’s surface. Usually, it’s safe to assume any Clusters of Differentiation is a protein.

Second, it is widely admitted by authors in the field that the complex organisms which appeared in the Cambrian would have required a host of new cell types. Here, for instance, is what P. V. Sukumaran, of the Geological Society of India, says in his paper, Cambrian Explosion of Life: the Big Bang in Metazoan Evolution (RESONANCE, September 2004, pp. 38-50):

Yet another feature of the Cambrian explosion is the quantum jump in biological complexity. The early Cambrian animals had roughly 50 cell types while the sponges that appeared a little earlier had only 5… (p. 44, sidebar)

Unicellular life is relatively simple; there is little division of labour and the single cell performs all functions of life. Obviously the genetic information content of unicellular organisms is relatively meagre. Multicellular life, on the other hand, requires more genetic information to carry out myriads of cellular functions as their cells are differentiated into different cell types, tissues and organs. But new cell types themselves require specialised proteins, and novel proteins arise from novel gene sequences, that is new genetic information. As the organisms that appeared in the Cambrian explosion had many more novel and specialised cell types than their prokaryotic ancestors, the amount of new genetic information that arose in the Cambrian explosion represents a large increase in biological information. (p. 47)

Third, it turns out that Dr. Meyer provided the very references that Rasmussen chides him for failing to supply, over 14 years ago, in his 2001 paper, The Cambrian Explosion: Biology’s Big Bang, which he co-authored with Paul Nelson and Paul Chien, which is listed on page 471 of the bibliography of Dr. Meyer’s book, Darwin’s Doubt. (Actually, the bibliography cites a later and slightly more polished 2003 version of the same paper.) Allow me to quote from pages 32-33 of the 2001 paper (emphases mine – VJT):

As noted, the new animals of the Cambrian explosion would have required many new cell types and, with them, many new types of proteins acting in close coordination. It follows, therefore, that if the neo-Darwinian mechanism cannot explain the origin of new cell types (and the systems of proteins they require), it cannot explain the origin of the Cambrian animals. Yet given the number of novel proteins required by even the most basic evolutionary transformations, this now seems to be precisely the case.

Consider, for example, the transition from a prokaryotic cell to a eukaryotic cell. This transition would have produced the first appearance of a novel cell type in the history of life. Compared to prokaryotes, eukaryotes have a more complex structure including a nucleus, a nuclear membrane, organelles (such as mitocondria, the endoplasmic recticulum, and the golgi apparatus), a complex cytoskeloton (with microtubulues, actin microfilaments117 and intermediate filaments) and motor molecules.118 Each of these features requires new proteins to build or service, and thus, as a consequence, more genetic information. (For example, the spooled chromosome in a modern eukaryotic yeast [Saccharomyces] cell has about 12.5 million base pairs, compared to about 580,000 base pairs in the prokaryote Mycoplasma.)119 The need for more genetic information in eukaryotic cells in turn requires a more efficient means of storing genetic information. Thus, unlike prokaryotic cells which store their genetic information on relatively simple circular chromosomes, the much more complex eukaryotic cells store information via a sophisticated spooling mechanism.120 Yet this single requirement — the need for a more efficient means of storing information — necessitates a host of other functional changes each of which requires new specialized proteins (and yet more genetic information) to maintain the integrity of the eukaryotic cellular system.

For example, nucleosome spooling requires a complex of specialized histones proteins (with multiple recognition and initiation factors) to form the spool around which the double stranded DNA can wind.121 Spooled eukaryotic DNA in turn uses “intron spacers,” (dedicated sections of non-coding DNA), in part to ensure a tight electrostatic fit between the nucleosome spool and the cords of DNA.122 This different means of storing DNA in turn requires a new type of DNA polymerase to help access, “read,” and copy genetic information during DNA replication. (Indeed, recent sequence comparisons show that prokaryotic and eukaryotic polymerases exhibit stark differences).123 Further, eukaryotes also require a different type of RNA polymerase to facilitate transcription. They also require a massive complex of five jointly necessary enzymes to facilitate recognition of the promoter sequence on the spooled DNA molecule.124 The presence of intron spacers in turn requires editing enzymes (including endonucleases, exonucleases and splicesomes) to remove the non-coding sections of the genetic text and to reconnect coding regions during gene expression.125 Spooling also requires a special method of capping or extending the end of the DNA text in order to prevent degradation of the text on linear (non-circular) eukaryotic chromosomes.126 The system used by eukaryotes to accomplish this end also requires a complex and uniquely specialized enzyme called a telomerase.127

Thus, one of the “simplest” evolutionary transitions, that from one type of single-celled organism to another, requires the origin of many tens of specialized novel proteins, many of which (such as the polymerases) alone represent massively complex, and improbably specified molecules.128 Moreover, many, if not most, of these novel proteins play functionally necessary roles in the eukaryotic system as a whole. Without specialized polymerases cell division and protein synthesis will shut down. Yet polymerases have many protein subunits containing many thousands of precisely sequenced amino acids. Without editing enzymes, the cell would produce many nonfunctional polypeptides, wasting vital ATP energy and clogging the tight spaces within the cytoplasm with many large useless molecules. Without tubulin and actin the eukaryotic cytoskeloton would collapse (or would never have formed). Indeed, without the cytoskeleton the eukaryotic cell can not maintain its shape, divide, or transport vital materials (such as enzymes, nutrients, signal molecules, or structural proteins).129 Without telomerases the genetic text on a linear spooled chromosome would degrade, again, preventing accurate DNA replication and eventually causing the parent cell to die.130

Even a rudimentary analysis of eukaryotic cells suggests the need for, not just one, but many novel proteins acting in close coordination to maintain (or establish) the functional integrity of the eukaryotic system. Indeed, the most basic structural changes necessary to a eukaryotic cell produce a kind of cascade of functional necessity entailing many other innovations of design, each of which necessitates specialized proteins. Yet the functional integration of the proteins parts in the eukaryotic cell poses a severe set of probabilistic obstacles to the neo-Darwinian mechanism, since the suite of proteins necessary to eukaryotic function must, by definition, arise before natural selection can act to select them.

References:
117 Russell F. Doolittle, “The Origins and Evolution of Eukaryotic Proteins,” Philosophical Transactions of the Royal Society of London B 349 (1995): 235-40.
118 Stephen L. Wolfe, Molecular and Cellular Biology (Belmont, CA: Wadsworth, 1993), pp. 3, 6-19.
119 Rebecca A. Clayton, Owen White, Karen A. Ketchum, and J. Craig Ventner, “The First Genome from the Third Domain of Life,” Nature 387 (1997): 4459-62.
120 Stephen L. Wolfe, Molecular and Cellular Biology, pp. 546-50.
121 Ibid.
122 H. Lodish, D. Baltimore, et. al., Molecular Cell Biology (New York: W.H. Freeman, 1994), pp. 347-48. Stephen L. Wolfe, Molecular and Cellular Biology, pp. 546-47.
123 Edgell and Russell Doolittle, “Archaebacterial genomics: the complete genome sequence of Methanococcus jannaschii,” BioEssays 19 (no. 1, 1997): 1-4. Michael Y. Galperin, D. Roland Walker, and Eugene V. Coonin, “Analogous Enzymes: Independent Inventions in Enzyme Evolution,” Genome Research 8 (1998): 779-90.
124 Stephen L. Wolfe, Molecular and Cellular Biology, pp. 580-81, 597.
125 Ibid., pp. 581-82, 598-600, 894-96.
126 Ibid., p. 975.
127 Ibid., pp. 955-975.
128 Ibid., p. 580.
129 Ibid., pp. 17-19.
130 Ibid., pp. 955-975.

And here’s a highly pertinent quote from pages 5-6 of the paper:

Each new cell type requires many new and specialized proteins. New proteins in turn require new genetic information encoded in DNA. Thus, an increase in the number of cell types implies (at a minimum) a considerable increase in the amount of specified genetic information. For example, molecular biologists have recently estimated that a minimally complex cell would require between 318 to 562 kilobase pairs of DNA to produce the proteins necessary to maintain life.20 Yet to build the proteins necessary to sustain a complex arthropod such as a trilobite would require an amount of DNA greater by several orders of magnitude (e.g., the genome size of the worm Caenorhabditis elegans is approximately 97 million base pairs21 while that of the fly Drosophila melanogaster (an arthropod), is approximately 120 million base pairs.22 For this reason, transitions from a single cell to colonies of cells to complex animals represent significant (and in principle measurable) increases in complexity and information content. Even C. elegans, a tiny worm about one millimeter long, comprises several highly specialized cells organized into unique tissues and organs with functions as diverse as gathering, processing and digesting food, eliminating waste, external protection, internal absorption and integration, circulation of fluids, perception, locomotion and reproduction. The functions corresponding to these specialized cells in turn require many specialized proteins, genes and cellular regulatory systems, representing an enormous increase in specified biological complexity. Figure 5 shows the complexity increase involved as one moves upward from cellular grade to tissue grade to organ grade life forms. Note the jump in complexity required to build complex Cambrian animals starting from, say, sponges in the late Precambrian. As Figure 5 shows Cambrian animals required 50 or more different cell types to function, whereas sponges required only 5 cell types.

(Note: Figure 5 can be viewed in this later version of the paper, where it is labeled as Figure 10 – VJT.)

References:
20 Mitsuhiro Itaya, “An estimation of the minimal genome size required for life,” FEBS Letters 362
(1995): 257-60. Claire Fraser, Jeannine D. Gocayne, Owen White, et. al., “The Minimal Gene Complement of Mycoplasma genitalium,” Science 270 (1995): 397-403. Arcady R. Mushegian and Eugene V. Koonin, “A minimal gene set for cellular life derived by comparison of complete bacterial genomes,” Proceedings of the National Academy of Sciences USA 93 (1996): 10268-73.
21 The C. elegans Sequencing Consortium, “Genome Sequence of the Nematode C. elegans: A Platform for Investigating Biology,” Science 282 (1998): 2012-18.
22 John Gerhart and Marc Kirschner, Cells, Embryos, and Evolution (London: Blackwell Science, 1997), p.
121

Did Dr. Meyer distort the words of geneticist Susumu Ohno?

Rasmussen also accuses Dr. Meyer of distorting the words of Susumu Ohno, a geneticist and evolutionary biologist whose work he discussed in chapter 10 of his book, Darwin’s Doubt:

It gets much worse, turns out Meyer is making assertions diametrically opposite to what his very very few references say. Remember what Meyer wrote above?

“The late geneticist and evolutionary biologist Susumu Ohno noted that Cambrian animals required complex new proteins such as, for example, lysyl oxidase in order to support their stout body structures.”

Well, much later in the same chapter, Meyer finally references Ohno:

“Third, building new animal forms requires generating far more than just one protein of modest length. New Cambrian animals would have required proteins much longer than 150 amino acids to perform necessary, specialized functions.21”

What is reference 21? It’s “21. Ohno, “The Notion of the Cambrian Pananimalia Genome.”

What does that reference say? Let’s look:

Reasons for Invoking the Presence of the Cambrian Pananimalia Genome.
Assuming the spontaneous mutation rate to be generous 10^-9 per base pair per year and also assuming no negative interference by natural selection, it still takes 10 million years to undergo 1% change in DNA base sequences. It follows that 6-10 million years in the evolutionary time scale is but a blink of an eye. The Cambrian explosion denoting the almost simultaneous emergence of nearly all the extant phyla of the kingdom Animalia within the time span of 6-10 million years can’t possibly be explained by mutational divergence of individual gene functions. Rather, it is more likely that all the animals involved in the Cambrian explosion were endowed with nearly the identical genome, with enormous morphological diversities displayed by multitudes of animal phyla being due to differential usages of the identical set of genes. This is the very reason for my proposal of the Cambrian pananimalia genome. This genome must have necessarily been related to those of Ediacarian predecessors, representing the phyla Porifera and Coelenterata, and possibly Annelida. Being related to the genome – possessed by the first set of multicellular organisms to emerge on this earth, it had to be rather modest in size. It should be recalled that the genome of modern day tunicates, representing subphylum Urochordata, is made of 1.8 x 10^8 DNA base pairs, which amounts to only 6% of the mammalian genome (9). The following are the more pertinent of the genes that were certain to have been included in the Cambrian pananimalia genome.”

The bold is my emphasis. I trust you can see the problem here. So, Meyer makes a single goddamn reference to support the claim that the Cambrian explosion required a lot of innovation of new proteins, folds, cell-types and so on. What do we find in that references? That Ohno is suggesting the direct opposite, that he is in fact supporting the standard evo-devo view that few regulatory changes were what happened, that the genes and proteins were already present and had long preceding evolutionary histories.

Once again, Rasmussen hasn’t done his homework. A little digging on my part revealed that Dr. Meyer had previously discussed the Dr. Ohno’s claims at considerable length and responded to those claims, in his 2001 paper, The Cambrian Explosion: Biology’s Big Bang, which he co-authored with Paul Nelson and Paul Chien (bolding mine – VJT):

Ironically, even attempts to avoid the difficulty posed by the Cambrian explosion often presuppose the need for such foresight. As noted, Susumo Uno, the originator of the hypothesis of macroevolution by gene duplication, has argued that mutation rates of extant genes are not sufficiently rapid to account for the amount of genetic information that arose suddenly in the Cambrian.114 Hence he posits the existence of a prior “pananimalian genome” that would have contained all the genetic information necessary to build every protein needed to build the Cambrian animals. His hypothesis envisions this genome arising in a hypothetical common ancestor well before the Cambrian explosion began. On this hypothesis, the differing expression of separate genes on the same master genome would explain the great variety of new animal forms found in the Cambrian strata.

While Ohno’s hypothesis does preserve the core evolutionary commitment to common descent (or monophyly), it nevertheless has a curious feature from the standpoint of neo-Darwinism. In particular, it envisions the pananimalian genome arising well before its expression in individual animals.115 Specific genes would have arisen well before they were used, needed or functionally advantageous. Hence, the individual genes within the pananimalian genome would have arisen in a way that, again, would have made them imperceptible to natural selection. This not only creates a problem for the neo-Darwinian mechanism, but it also seems to suggest, as Simon Conway Morris has recently intimated,116 the need for foresight or teleology to explain the Cambrian explosion. Indeed, the origin of a massive, unexpressed pre-Cambrian genome containing all the information necessary to build the proteins required by not-yet-existent Cambrian animals, would strongly suggest intelligent foresight or design at work in whatever process gave rise to the pananimalian genome. (pp. 31-32)

In short: Dr. Meyer was not only aware that Dr. Ohno had proposed the existence of a pananimalian genome; he also explicitly referred to it in his 2001 paper, in order to demonstrate that Intelligent Design would be the best explanation of such a genome.

I’ll leave it to my readers to decide whether it is Dr. Meyer or Rasmussen who is guilty of “extremely shoddy scholarship.” Let me conclude by recalling an old saying: “People who live in glass houses shouldn’t throw stones.”

177 Replies to “This is embarrassing: “Darwin’s Doubt” debunker is 14 years behind the times

  1. 1
    NickMatzke_UD says:

    VJ Torley, your post is silly in several ways:

    1. “New genes” and “new proteins” are not the same thing as “new protein folds”. You can have many different kinds of proteins that all draw from the same folds. You can’t quote sources talking about new genes/new proteins/new information and just blithely assume this automatically means new folds. Rasmussen gets this, Meyer misses this, you miss this.

    2. The pan-animalian genome idea means that all of these animals are built with not only the same basic folds, but the same basic gene set. This is dramatically less of an “information explosion” than would be required if they all needed different genes.

    (All that said, Ohno isn’t even particularly an expert on the Cambrian Explosion. The pan-animalian genome idea is a good one nevertheless. But he misses things, which the ID advocates then naively take as gospel truth, since they have such a blind and un-nuanced idea of “authority” in science.

    E.g., because he’s not a paleontologist, one thing Ohno misses, IIRC, is that there is clear evidence of bilaterians in the Precambrian — trackways and burrows indicating billaterial symmetry, a coelom, etc., and these continually increase in complexity through the small shelly fossils, only reaching the “classic” Cambrian Explosion tens of millions of years later. This is all true regardless of one’s interpretation of the Edicarans etc. Thus, it’s idiotic to say, as Meyer does, that Ohno’s hypothesis means “the pananimalian genome ar[ose] well before its expression in individual animals.” Fossil traces of bilaterians are there before the Explosion, they had worm-level complexity, all of those common genes between all the phyla basically are what is required to specify a bilaterian body plan, which is what worms have.

    3. Bringing in the origin of eukaryotes is also silly, since eukaryotes arose probably a billion years before the Cambrian. Whether or not new protein folds originated with eukaryotes (probably, although many many folds are shared between eukaryotes and prokaryotes), this is in no possible way an argument that new folds originated in the Cambrian. This is totally obvious! How can you not get this is, in a post allegedly taking on Rasmussen head-on?

    Even the intended argument is hazy, but seems to be something like: the origin of the first eukaryotic cell, a “simple” transition, required lots of new proteins and protein folds, therefore the origin of new cell types must also. But that’s just crazy. Different cell types in a multicellular eukaryote will have much more in common than a eukaryote cell and a prokaryote cell. The origin of eukaryotes is probably the biggest and most fundamental evolutionary event apart from the origin of life itself. The origin of multicellularity, the Cambrian Explosion (not the same thing as the origin of multicellularity, another thing ID/creationists often miss), etc. are all minor by comparison.

    These kinds of catastrophic, fundamental mistakes and lack of knowledge of absolute basics — which are totally obvious to anyone who has a basic grasp of the field — are exactly why biologists are so dismissive of Meyer, ID, and UD. Imagine if someone went around claiming that the U.S. Constitution was fatally flawed, and then claimed that the First Amendment was about gun control. Most people would just shake their heads and walk away, concluding that kooks who can’t get these basics right aren’t worth listening to.

  2. 2
    anthropic says:

    2. “The pan-animalian genome idea means that all of these animals are built with not only the same basic folds, but the same basic gene set. This is dramatically less of an “information explosion” than would be required if they all needed different genes.”

    So if someone chips rocks to make a spearhead, and then someone else uses the minerals in the rock to build a skyscraper or a computer, there has been no information explosion.

    You’re kidding, right?

  3. 3
    Mung says:

    1. “New genes” and “new proteins” are not the same thing as “new protein folds”. You can have many different kinds of proteins that all draw from the same folds. You can’t quote sources talking about new genes/new proteins/new information and just blithely assume this automatically means new folds. Rasmussen gets this, Meyer misses this, you miss this.

    Oh please. This is just silly. Actually, it’s just false.

    Meyer clearly understands the difference and VJT doesn’t even address protein folds.

  4. 4
    Mung says:

    The notion of the Cambrian pananimalia genome.

    People can see for themselves whether what Nick says can be found in the paper.

  5. 5
    Barry Arrington says:

    NickMatzke

    VJ Torley, your post is silly in several ways.

    But you will have to admit it is not as silly as when you said that 500 coins on a table all heads would “not really” warrant a design inference. Nick, you still hold the record for the single stupidest thing ever said on UD. I suspect your record is like DiMaggio’s consecutive games with a hit record — theoretically breakable but not practically.

  6. 6
    Mung says:

    Nick Matzke:

    But he misses things, which the ID advocates then naively take as gospel truth, since they have such a blind and un-nuanced idea of “authority” in science.

    All these things Ohno misses and fails to mention, somehow ID advocates take this stuff that was never written and turn it into gospel truth. That’s hilarious. Really.

  7. 7
    Mung says:

    Starting at this link people can read quotes from the Erwin and Valentine book The Cambrian Explosion: The Construction of Animal Biodiversity.

    Nick’s probably not read it.

    Starting at this link people can read quotes from the T. Ryan Gregory edited book The Evolution of the Genome

    Nick’s probably not read that one either.

  8. 8
    NickMatzke_UD says:

    Oh please. This is just silly. Actually, it’s just false.

    Meyer clearly understands the difference and VJT doesn’t even address protein folds.

    Dood! Read the opening post. Search on the word “fold”. VJ Torley quotes Rasmussen. Rasmussun is talking about folds. In the part that Torley quotes.

    It’s true VJT doesn’t really address folds, but that’s just more evidence that VJT’s “rebuttal” is totally incomprehending of Rasmussen’s critique of Meyer. VJT couldn’t find anything in Meyer addressing the hole that Rasmussen points out, so he ignorantly quoted a bunch of irrelevant stuff, because I guess Quoting Big Words N Stuff constitutes a rebuttal in his book.

    All the other irrelevanices in this thread are even more supporting evidence that ID guys just don’t know what they are talking about.

  9. 9
    RexTugwell says:

    it is not as silly as when you said that 500 coins on a table all heads would “not really” warrant a design inference. Nick, you still hold the record for the single stupidest thing ever said on UD.

    Did Nick really make such a ridiculous claim? That explains everything. Hey Nick, how’s your review of Denton’s book coming along?

  10. 10
    Mapou says:

    Nick:

    These kinds of catastrophic, fundamental mistakes and lack of knowledge of absolute basics — which are totally obvious to anyone who has a basic grasp of the field — are exactly why biologists are so dismissive of Meyer, ID, and UD.

    And yet, one does not need to be a biologist to understand that the combinatorial explosion kills ANY stochastic search mechanism dead. This means RM+NS and the whole abiogenesis nonsense.

    So they give PhDs in biology for flipping burgers, now? You people are both mentally and morally challenged.

  11. 11
    Mung says:

    Mung: Meyer clearly understands the difference and VJT doesn’t even address protein folds.

    Nick Matzke: It’s true VJT doesn’t really address folds

    LoL. Dood. I know. That’s what I said.

    …but that’s just more evidence that VJT’s “rebuttal” is totally incomprehending of Rasmussen’s critique of Meyer.

    Move the goalposts. Fine, Nick.

  12. 12
    Mung says:

    The origin of multicellularity, the Cambrian Explosion (not the same thing as the origin of multicellularity, another thing ID/creationists often miss), etc. are all minor by comparison.

    Whatever you say Nick.

    There’s a very nice figure in the Erwin/Valentine book. Figure 9.2 on page 299.

  13. 13
    CLAVDIVS says:

    Mapou – What do you mean by ‘combinatorial explosion’ in this context?

  14. 14
    Mapou says:

    CLAVDIVS @13,

    Anytime one must create a new useful protein, one is faced with a combinatorial explosion that kills any stochastic search. The search space is so huge, it might as well be called “infinite”.

    PS. It’s all extremely simple math, the kind that Darwinists seem to have a lot of trouble grasping.

  15. 15
    bpragmatic says:

    Matzke:

    New “genes” and “new proteins” are not the same thing as “new protein folds”.

    Until you can empirically demonstrate through multiple scientific test results, repeatedly, and with independent verification that the alleged mechanisms of evolution can produce the molecular machinery required to produce any old functioning protein with contextual relevance of what a so called primitive alleged precursor organism has need of, your argument regarding “New “genes” and “new proteins” are not the same thing as “new protein folds”…. is
    MEANINGLESS within this context.

    It is UNBELIEVABLE someone with this perspective can actually get some sort of academic degree under the guise of “science”. And actually be employed by a publicly funded institution to represent some sort of “scientific” endeavor. And not understand the lack of true SCIENCE in their public proclamations that are mere philosophical conjecture.

  16. 16
    Barry Arrington says:

    Rex @ 9:

    Did Nick really make such a ridiculous claim?

    Indeed he did Rex. See comment 13 (and the comments leading up to it for context) of this post.

  17. 17
    Mung says:

    In contrast to Matzke’s “there’s nothing new here folks, move along.”

    Creatures of Accident: The Rise of the Animal Kingdom

    Yes, there really are differences between a sponge and a jellyfish.

    Maybe Nick believes in front-loading. 🙂

  18. 18
    gpuccio says:

    Of course new folds, superfamilies and families of proteins appear in metazoa. Just look at this paper:

    http://www.plosone.org/article.....tation=PDF

    Table 1 attributes 58 new domains and 557 new domain combinations at the root of metazoa.

    OK, it’s not exactly as much as the 1984 domains and 4631 domain combinations at the root of cellular organisms, but we certainly know that OOL is a much bigger problem for darwinists than the origin of metazoa in terms of origin of protein coding sequences. That’s probably why Meyer dedicated his previous book to OOL, and dealed with the Cambrian explosion after that.

    But the important points are:

    a) Metazoa certainly require new protein folds, protein superfamilies and proteins families, and new combinations too, in a rather abundant neasure. It is really silly to try to deny that.

    b) The origin of metazoa certainly requires a lot more of new epigenetic information. Unless darwinists still want to believe that cell differentiation is just a lucky way of using what already is there, in spite of all that epigenetics is discovering, then certainly the evolution from metazoa on is mainly an evolution of epigenetic procedures.

    It is true that the bulk of protein sequences and folds appears at OOL. Many of the most important acquisitions in that realm are already present in LUCA.

    The second main jump is certainly the appearance of eukaryotes (492 new domains, 6056 new domain combinations, according to that paper). And the third big jump is the appearance of metazoa. In terms of protein sequences.

    On the contrary, there are very good reasons to believe, even with our still rudimentary understanding of epigenetics, that the acquisition of new epigenetic information follows an opposite trend: some of it is already in prokaryotes, but a lot of it appears in eukaryotes, and the biggest jump of all takes place with the appearance of metazoa.

    IOWs, the desing of life works at the beginning prevalently on the gross structure of the final effectors (proteins), while gradually it shifts to much more complex control networks (epigenetics).

    But again, Meyer’s statements about new protein folds in metazoa are simply true and obvious.

  19. 19
    RexTugwell says:

    Thank you for the link, Barry. A truly fascinating look into the mind of a committed Darwinist with a zero-concession policy.

    Matzke snivels

    …are exactly why biologists are so dismissive of Meyer, ID, and UD

    Right. And yet here you are Nick, continuing to haunt the pages of UD year after year. Do you spend as much time at websites advocating geocentrism?

    Remember this?

    It’s over for the Discovery Institute. Turn out the lights. The fat lady has sung. The emperor of ID has no clothes. The bluff is over. Oh sure, they’ll continue to pump out the blather. They’ll find more funding, at least for a while, from some committed ideologue or another. But no one with any objectivity will take them seriously any longer as scientists.

  20. 20
    News says:

    All great stuff. Keep in mind, though, that in these times, fact and evidence matter very little compared to narrative and spin.

    Matzke can say anything he likes, as long as the narrative an spn put off the day of reckoning for those he speaks for.

    In fact, if science were simply to devolve into finding support for naturalism, that day would never come.

    Science would decline but not everyone would be wore off for that.

  21. 21
    bornagain77 says:

    Actually it has recently been found that unique ORFan proteins are a far bigger problem than Darwinists would have preferred to believe:

    Unexpected features of the dark proteome – Oct. 2015
    Excerpt: Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions,,,
    We deliberately chose this stringent definition of “darkness,” so we can be confident that the dark proteome has completely unknown structure.,,,
    ,,,in eukaryotes and viruses, about half (44–54%) of the proteome was dark (Fig. 1B). Of the total dark proteome, nearly half (34–52%) comprised dark proteins.
    We repeated the above analysis using an even more stringent definition for darkness—combining PMP (2) and Aquaria (SI Methods) — but this had little effect (Fig. S1).,,,
    Lower Evolutionary Reuse.
    For each protein, we calculated how frequently any part of its sequence has been reused across all other known proteins (SI Methods). Dark proteins were reused much less frequently than nondark proteins (Fig. 4 C and Fig. S8), suggesting that dark proteins may be newly evolved proteins or rare proteins adapted to specific functional niches. This result was partly expected, given how darkness was defined and given the progress of structural genomics in targeting large protein families with unknown structure (8). Low evolutionary reuse also partly explains why dark proteins have few known interactions (Fig. 4 B and Fig. S8), because many interactions are inferred by homology (33).
    http://www.pnas.org/content/ea.....2.full.pdf

    The Dark Proteome and Dark Evolution – Evolution Did It – Cornelius Hunter – Nov. 23, 2015
    Excerpt: “Thus, our results suggest that many of the uncharacterized orphan sequences … are indeed real proteins.”
    http://darwins-god.blogspot.co.....ution.html

    Moreover, it is not as if Darwinists have ever demonstrated the origin of a new protein by unguided Darwinian processes and that they therefore have a plausible mechanism in place for explaining the origin of new proteins.
    The last four decades worth of lab work are surveyed here, and no evidence for Darwinian evolution creating new proteins surfaces. In fact it is found that unguided material processes excel at breaking things rather than creating anything new:

    “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain – Michael Behe – December 2010
    Excerpt: In its most recent issue The Quarterly Review of Biology has published a review by myself of laboratory evolution experiments of microbes going back four decades.,,, The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.,,, I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain.
    http://behe.uncommondescent.co.....evolution/

    More from Behe

    Michael Behe – Observed (1 in 10^20) Edge of Evolution – video – Lecture delivered in April 2015 at Colorado School of Mines
    25:56 minute quote – “This is not an argument anymore that Darwinism cannot make complex functional systems; it is an observation that it does not.”
    https://www.youtube.com/watch?v=9svV8wNUqvA

    Kenneth Miller Steps on Darwin’s Achilles Heel – Michael Behe – January 17, 2015
    Excerpt: Enter Achilles and his heel. It turns out that the odds are much better for atovaquone resistance because only one particular malaria mutation is required for resistance. The odds are astronomical for chloroquine because a minimum of two particular malaria mutations are required for resistance. Just one mutation won’t do it. For Darwinism, that is the troublesome significance of Summers et al.: “The findings presented here reveal that the minimum requirement for (low) CQ transport activity … is two mutations.”
    Darwinism is hounded relentlessly by an unshakeable limitation: if it has to skip even a single tiny step — that is, if an evolutionary pathway includes a deleterious or even neutral mutation — then the probability of finding the pathway by random mutation decreases exponentially. If even a few more unselected mutations are needed, the likelihood rapidly fades away.,,,
    So what should we conclude from all this? Miller grants for purposes of discussion that the likelihood of developing a new protein binding site is 1 in 10^20. Now, suppose that, in order to acquire some new, useful property, not just one but two new protein-binding sites had to develop. In that case the odds would be the multiple of the two separate events — about 1 in 10^40, which is somewhat more than the number of cells that have existed on earth in the history of life. That seems like a reasonable place to set the likely limit to Darwinism, to draw the edge of evolution.
    http://www.evolutionnews.org/2.....92771.html

    As Behe touched upon, the numbers coming out for the evolution of novel proteins by unguided processes are prohibitive:

    The Evolutionary Accessibility of New Enzyme Functions: A Case Study from the Biotin Pathway – Ann K. Gauger and Douglas D. Axe – April 2011
    Excerpt: We infer from the mutants examined that successful functional conversion would in this case require seven or more nucleotide substitutions. But evolutionary innovations requiring that many changes would be extraordinarily rare, becoming probable only on timescales much longer than the age of life on earth.
    http://bio-complexity.org/ojs/.....O-C.2011.1

    “Biologist Douglas Axe on Evolution’s (non) Ability to Produce New (Protein) Functions ” – video
    Quote: It turns out once you get above the number six [changes] — and even at lower numbers actually — but once you get above the number six you can pretty decisively rule out an evolutionary transition because it would take far more time than there is on planet Earth and larger populations than there are on planet Earth.
    https://www.youtube.com/watch?v=8ZiLsXO-dYo

    “Enzyme Families — Shared Evolutionary History or Shared Design?” – Ann Gauger – December 4, 2014
    Excerpt: If enzymes can’t be recruited to genuinely new functions by unguided means, no matter how similar they are, the evolutionary story is false.,,,
    Taken together, since we found no enzyme that was within one mutation of cooption, the total number of mutations needed is at least four: one for duplication, one for over-production, and two or more single base changes. The waiting time required to achieve four mutations is 10^15 years. That’s longer than the age of the universe. The real waiting time is likely to be much greater, since the two most likely candidate enzymes failed to be coopted by double mutations.
    We have now addressed two objections raised by our critics: that we didn’t test the right mutation(s), and that we didn’t use the right starting point. We tested all possible single base changes in nine different enzymes, Those nine enzymes are the most structurally similar of BioF’s entire family We also tested 70 percent of double mutations in the two closest enzymes of those nine.
    Finally, some have said we should have used the ancestral enzyme as our starting point, because they believe modern enzymes are somehow different from ancient ones. Why do they think that? It’s because modern enzymes can’t be coopted to anything except trivial changes in function. In other words, they don’t evolve!
    That is precisely the point we are making.
    http://www.evolutionnews.org/2.....91701.html

    “Shared Evolutionary History or Shared Design?” – Ann Gauger – January 1, 2015
    Excerpt: The waiting time required to achieve four mutations is 10^15 years. That’s longer than the age of the universe. The real waiting time is likely to be much greater, since the two most likely candidate enzymes failed to be coopted by double mutations.
    per ENV

  22. 22
    Florabama says:

    Nick Matzke — biology’s Baghdad Bob.

  23. 23
    Barry Arrington says:

    Nick,

    Ohno misses, IIRC, is that there is clear evidence of bilaterians in the Precambrian — trackways and burrows indicating billaterial symmetry, a coelom, etc., and these continually increase in complexity through the small shelly fossils

    It appears that you are admitting there are no actual bilaterian fossils in the precambrian layers; instead, you are inferring they nevertheless existed based on certain “trackways and burrows.”

    Is that what you are saying Nick? If not, you need to clear it up, because it certainly appears that is what you are saying. If yes, *palm-forehead* you people are getting desperate. I will give you some time to clear this up before I make an OP of it.

  24. 24
    Mung says:

    I heard that the Bilateria appeared before the Porifera. Is that true Nick?

  25. 25
    Mung says:

    Nick comes stops by and tries to smear Meyer and VJT. Is he reduced to trolling these days?

    And for what it’s worth, Nick, if you’re still watching, I think this piece at ENV was in very poor taste and I hope West will issue an apology.

  26. 26
    Mung says:

    gpuccio:

    But again, Meyer’s statements about new protein folds in metazoa are simply true and obvious.

    Meyer claims that new cell type and organs appeared and that new genes and proteins appeared do, to me at least, not seem to require that he cite his sources. They seem to me obvious.

    But if you’re going to be an anti-ID skeptic you may as well go whole hog and blame Meyer for poor scholarship because he doesn’t provide a source for everything he says.

    Whether new protein folds were required though, seems less obvious. And even if we could show that new protein folds also appeared, wouldn’t phylogenetic analysis push them way back in time so that a committed anti-Meyer skeptic could claim they were already there, in advance?

    The last refuge of the anti-ID skeptic, it was already there, in the beginning. The irony. 🙂

    Thanks gpuccio!

  27. 27
    Mapou says:

    Nick:

    E.g., because he’s not a paleontologist, one thing Ohno misses, IIRC, is that there is clear evidence of bilaterians in the Precambrian — trackways and burrows indicating billaterial symmetry, a coelom, etc., and these continually increase in complexity through the small shelly fossils, only reaching the “classic” Cambrian Explosion tens of millions of years later.

    If true, so what?. Why is this evidence for Darwinian evolution and not for Design evolution? Besides, 10 million years is not nearly enough to go from preCambrian to Cambrian via random incremental evolutionary steps. No amount of time is ever enough. Why? Simply because the combinatorial explosion kills ANY stochastic search mechanism dead. Read and weep, troll.

  28. 28
    gpuccio says:

    Mung:

    The paper I quoted deals with protein families, but I am rather sure that the new domain families at the root of metazoa include new protein superfamilies and folds.

    However, the important point is another one: the huge epigenetic information which allows metazoa to appear includes also a lot of new information at the level of protein coding genes. Even those folds and superfamilies which in some way already existed in single celled eukaryotes, or even in prokaryotes, have to change a lot to support the new functions implied in cell differentiation.

    Moreover, the whole network of transcription factors, the systems to generate and control cell asymmetry and gradients, the complex interactions between promoters and enhancers, the regulation of chromatin 3d structure, and so on, all require consistent changes and acquisitions at the level of both coding and non coding DNA, and probably at other levels that we still don’t understand.

    However you interpret natural history and the appearance of metazoa, no range of time would have been enough for that in a neo-darwinian context, least of all the few tens of million years which seem to be implied in the Cambrian explosion.

    The problem is the same for OOL, where a huge quantity of basic protein structure information appears in a range of time which is certainly not so large, since when our planer became compatible with life to when LUCA inhabited it.

    And the same is true for the appearance of eukaryotes, which remains probably the least well established event with regards to its chronology, but which is certainly one of the most amazing engineering innovations in the whole history of the design of life.

  29. 29
    vjtorley says:

    Hi Nick Matzke,

    Thank you for your comments. I’ll address your objections in reverse order. You write:

    Bringing in the origin of eukaryotes is also silly, since eukaryotes arose probably a billion years before the Cambrian. Whether or not new protein folds originated with eukaryotes (probably, although many many folds are shared between eukaryotes and prokaryotes), this is in no possible way an argument that new folds originated in the Cambrian. This is totally obvious! How can you not get this is, in a post allegedly taking on Rasmussen head-on?

    Numbers are easy for me to remember. I carry a geological timescale around with me, in my head. So I’m perfectly well aware that prokaryotes and eukaryotes probably diverged over two billion years ago, long before the Cambrian.

    The reason why I think the timing of the divergence is irrelevant is that Dr. Stephen Meyer does, too. Frankly I couldn’t care less whether the new proteins required by complex life-forms appeared in the Cambrian or in the much more distant pre-Cambrian. The central question is: how did they appear, and more specifically, could they have arisen via an undirected process? Meyer’s contention is that even if we grant evolutionists billions of years (rather than just a few million years), there still wouldn’t have been enough time for these proteins to have arisen by unguided natural processes.

    Dr. Meyer brings this point out in the video showing his reflections on the debate he had with Dr. Charles Marshall (August 5, 2014), which you appear not to have viewed. Meyer declares [2:18-3:49] (emphases mine – VJT):

    Another interesting point that came out in the debate with Marshall was the way in which he pushed the information problem back into the pre-Cambrian. And he posited the possibility that there might have been a pre-Cambrian pan-animalian genome, as it’s sometimes called: a vast store of genetic information in some ancestral form which hasn’t been documented in the fossil record but which we might infer by some other means. And I pointed out in my response to him that that might be the case, but that still doesn’t solve the information problem, because you’ve just pushed the origin of that information back into the dark recesses of the pre-Cambrian: a cryptic history that hasn’t been documented in the fossil record. But even if some ancestral form existed, that had all the information for all the animals that came later, you’d still have to explain the origin of those genes.

    Now Marshall took my response to be something of a concession – that maybe the pre-Cambrian animals might have evolved from some pre-Cambrian common ancestor. And maybe it is a concession of sorts: it’s certainly a possibility. It doesn’t look very plausible to me from the fossil evidence or the genetic evidence, but maybe there was such an animal. But it’s not really a concession on the key information argument, that you still need to explain those genes. And Marshall repeatedly presupposed but didn’t explain genetic information.

    Meyer says the same thing in an earlier response to Marshall (October 7, 2013):

    The article “The Causes of the Cambrian Explosion,” which accompanies Marshall’s review of my book in Science, also presupposes such a universal gene toolkit and suggests that it might have arisen 100 million years or more before the explosion of animal life in the Cambrian period.18

    Nevertheless, this question-begging assumption does not solve the central problem posed by Darwin’s Doubt — that of the origin of the genetic (and epigenetic) information necessary to produce the Cambrian animals. It merely pushes the problem back several tens or hundreds of millions of years, assuming that such a universal genetic toolkit ever existed… In any case, Marshall does not explain how the neo-Darwinian mechanism could have overcome the combinatorial search problem described in Darwin’s Doubt to produce even the new genetic information necessary to build new proteins and Cambrian animals.

    From the foregoing quotes, I hope you can see that the timing of the Cambrian explosion isn’t central to Meyer’s argument: it’s peripheral. Even if the proteins and genes were already there in the pre-Cambrian, we need to explain how they originated.

  30. 30
    vjtorley says:

    Hi Nick Matzke,

    You also write:

    The pan-animalian genome idea means that all of these animals are built with not only the same basic folds, but the same basic gene set. This is dramatically less of an “information explosion” than would be required if they all needed different genes…

    [I]t’s idiotic to say, as Meyer does, that Ohno’s hypothesis means “the pananimalian genome ar[ose] well before its expression in individual animals.” Fossil traces of bilaterians are there before the Explosion, they had worm-level complexity, all of those common genes between all the phyla basically are what is required to specify a bilaterian body plan, which is what worms have.

    It’s quite obvious to me that when Dr. Meyer wrote that Ohno’s hypothesis means that “the pananimalian genome ar[ose] well before its expression in individual animals,” he was referring to individual kinds of animals – in particular, phyla. The bilaterian tracks which you refer to are not clearly identifiable as members of any particular phylum: they predate that. All we can say is that they were worms.

    Moreover, even if it’s the case that all animals share the same set of genes (and proteins), it would still need to be a very large set. At the very minimum, we’re talking thousands here – not hundreds or dozens. The origin of this vast set needs to be accounted for.

  31. 31
    vjtorley says:

    Hi Nick Matzke,

    You write:

    “New genes” and “new proteins” are not the same thing as “new protein folds”. You can have many different kinds of proteins that all draw from the same folds. You can’t quote sources talking about new genes/new proteins/new information and just blithely assume this automatically means new folds. Rasmussen gets this, Meyer misses this, you miss this.

    I don’t know what Rasmussen’s background is, so I’d be wary of assuming that he “gets” anything about new protein folds. But if you’ll have a look at his post, you’ll see that what he takes issue with is Dr. Meyer’s claim that “the Cambrian explosion required a lot of innovation of new proteins, folds, cell-types and so on” (emphasis mine). In my post, I deliberately chose to focus on new proteins. Thus my first heading in my OP is: “Do new cell types require new kinds of proteins?”

    I should add that the question of how many protein folds exist in Nature is not well-defined, as this summary by Professor Andrew Torda points out. It acknowledges that “folds are not well defined,” that “similar folds are not easy to recognise” and that statistical methods for counting protein folds “all use an arbitrary definition of fold.” The paper’s answer to the question of how many folds exist is: “as many as you want,” and it adds that while 10^3 smaller structures (of 50 residues) have been identified, there are some “very big numbers for larger structures.” In its statistical summary, it declares that “estimates vary from 1 000 to 4 000,” with a few estimates going as high as 8,000.

    For my part, I’ll leave the question of how many protein folds there are to the experts. All I can say is: there are a lot, and we can certainly say that there are thousands. I can’t see how that helps your case, Nick. You still need to explain how all these folds arose in the first place. And as Dr. Douglas Axe has pointed out, The Case Against a Darwinian Origin of Protein Folds is mathematically overwhelming.

  32. 32
    NickMatzke_UD says:

    Of course new folds, superfamilies and families of proteins appear in metazoa. Just look at this paper:

    http://www.plosone.org/article…..tation=PDF

    Table 1 attributes 58 new domains and 557 new domain combinations at the root of metazoa.

    Ah, finally some relevant literature. Funny that everyone before this was talking irrelevancies.

    And actually, that paper says only 17 new domains at the root of bilateria, which is what the Cambrian Explosion is about (sponges and cnidarians are older). (Another way to look at this number is to say that thousands of domains are shared between bilaterians, cnidarians, and sponges, and only 17 domains are unique to bilaterians.)

    Given that there are thousands of domains, 17 new ones in that part of the tree of life is not any kind of “Explosion” or even particularly surprising. “1% increase in the number of domains” would have a rather different ring to it than Meyer’s rhetoric.

    (An aside: I tend to think these numbers, based on homology searches, are more about how far back homology can be detected for proteins with different average rates of sequence change. Fast proteins will have domains that appear to “emerge” after the Cambrian, medium-rate proteins with just the right rate will appear on that bilaterian branch, slower proteins will be traced back further.)

    The question remains, gpuccio: Was VJ Torley’s rebuttal even in the ballpark? Were he and his defenders before you anywhere in the zone of talking sense about the issues raised by Rasmussen?

  33. 33
    NickMatzke_UD says:

    VJ Torley writes,

    But if you’ll have a look at his post, you’ll see that what he takes issue with is Dr. Meyer’s claim that “the Cambrian explosion required a lot of innovation of new proteins, folds, cell-types and so on” (emphasis mine). In my post, I deliberately chose to focus on new proteins. Thus my first heading in my OP is: “Do new cell types require new kinds of proteins?”

    Heh, nice try to retcon this, but no. Rasmussen’s post is mostly about *folds*. It’s all throughout his post. And the quote you put prominently in your opening post was about folds, not proteins. This is the quote of Rasmussen you yourself put forward:

    Having read the book, a recurring phenomenon is that Meyer time and again makes claims without providing any references for them. Take for instance the claim that the Cambrian explosion requires lots of new protein folds, from Chapter 10 The Origin of Genes and Proteins:

    (Rasmussen proceeds to quote from Meyer’s book, on which he comments below – VJT.)

    In the whole section Meyer dedicates to the origin of novel folds, he makes zero references that actually substantiate [his assertion] that the [C]ambrian diversification, or indeed any kind of speciation, or the [appearance of] new cells types or organs, require[d] new protein folds. ZERO. Not one single reference that supports these claims. At first it reads like what I quote[d] above, lots of claims, no references. Later on he eventually cites the work of Douglas Axe that atte[m]pts to address how hard it is to evolve new folds (and that work has its own set of problems, but never mind that). Axe makes the same claim in his ID-journal Bio-complexity papers (which eventually Meyers cites), but in Axe’s papers, that claim is not supported by any reference either. It’s simply asserted as fact. In other words, Meyer makes a claim, then cites Axe making the same claim. Neither of them give a reference.

    …which you then attempted to rebut with total irrelevancies which would only make sense to someone unclear on the difference between mere new genes/proteins and new folds.

  34. 34
    NickMatzke_UD says:

    For my part, I’ll leave the question of how many protein folds there are to the experts. All I can say is: there are a lot, and we can certainly say that there are thousands. I can’t see how that helps your case, Nick. You still need to explain how all these folds arose in the first place. And as Dr. Douglas Axe has pointed out, The Case Against a Darwinian Origin of Protein Folds is mathematically overwhelming.

    Even if true (it’s not), none of this is particularly relevant to the Cambrian Explosion, which is allegedly what Meyer’s book was about, because the Cambrian phyla share virtually all of their folds with each other and with pre-Cambrian Explosion organisms. The origin of new folds is just not that relevant. But Meyer tries to shoehorn it in there for some reason, without anything that actually supports the idea, and in total ignorance of the actual literature on the topic which suggests that protein folds trace back way further.

    Like Rasmussen said.

    (And, like I said back in 2013, reviewing Meyer:

    “The basic protein domains mostly originated very far back in evolutionary history, where things like ultrahigh population sizes help out, as well as the fact that there are probably a fairly limited number of protein domains, and the fact that point mutations and rearrangements can, on occasion, produce new or modified protein folds, in some cases without having much effect on enzymatic activity.”)

  35. 35
    NickMatzke_UD says:

    The reason why I think the timing of the divergence is irrelevant is that Dr. Stephen Meyer does, too. Frankly I couldn’t care less whether the new proteins required by complex life-forms appeared in the Cambrian or in the much more distant pre-Cambrian. The central question is: how did they appear, and more specifically, could they have arisen via an undirected process? Meyer’s contention is that even if we grant evolutionists billions of years (rather than just a few million years), there still wouldn’t have been enough time for these proteins to have arisen by unguided natural processes.

    This is retconning too. Meyer’s book emphasizes again and again the alleged high rate of information acquisition, allegedly in the “Cambrian Explosion”, and how this “amount” of new information in this amount of time is an ID argument, It’s true that he also seems to think that any new information or new gene, anywhere, must be the product of intelligent intervention (a silly position — even Behe and Berlinski concede that evolution can produce new genes with new functions), but this only became part of the “timing is irrelevant” rebuttal after critics pointed out just how silly it was to assert that the Cambrian Explosion itself took lots of new genes, proteins, folds, etc.

  36. 36
    NickMatzke_UD says:

    Also — the whole idea that “timing isn’t central” to an argument about an “explosion” is ridiculous. If the word “explosion” means anything, it means that whatever you are examining is changing much faster than usual during the “explosion.”

    Morphology changes quickly during the Cambrian Explosion, and Meyer made the mistake of thinking that this must have meant lots of “new information” and thus new genes, proteins, and folds. But it just ain’t so, as anyone actually familiar with the topic would have known. The last 2 years have just been attempts to hide this mistake from the naive ID fans.

  37. 37
    Virgil Cain says:

    Earth to Nick Matzke- You don’t have any idea what is required in order to account for the diversity of life in the Cambrian nor any epoch. There aren’t any known evolutionary mechanisms capable of producing it. And everyone familiar with the topic knows that.

    And no intervention is required if the organisms were designed to evolve and evolved by design. It’s amazing that after all of these years you still misrepresent ID and what is being debated. Shame on you, your willful ignorance and your overselling of evolutionism.

    Talk about naive…

  38. 38
    NickMatzke_UD says:

    Then there’s how Rasmussen himself describes his own post:

    He doesn’t give a single reference that shows the cambrian diversification required new protein folds to evolve.

    He asks in his title “Do new cell types require new kinds of proteins?”

    What’s a “new kind” of protein? We’re talking about folds, Vincent.

  39. 39
    NickMatzke_UD says:

    Meyer’s original argument, as quoted by Rasmussen:

    “In some cases new proteins, while functionally new, would perform their different functions with essentially the same fold or tertiary structure as earlier proteins. But more often, proteins capable of performing new functions require new folds to perform these functions. That means that explosions of new life-forms must have involved bursts of new protein folds as well.”

  40. 40
    Virgil Cain says:

    Nick, You don’t have an argument and you don’t have a mechanism capable of explaining the Cambrian diversity.

    You really should focus on that.

  41. 41
    Mapou says:

    Matzke’s on fire. It’s a sign of panic and despair in the Darwinist camp.

  42. 42
    Mung says:

    Nick Matzke:

    Were he and his defenders before you anywhere in the zone of talking sense about the issues raised by Rasmussen?

    What issues, Nick? Rumraket asserts [now] that he’s only raised one issue, that of protein folds. You two ought to get on the same page, else you’re the one introducing irrelevancies.

  43. 43
    Mung says:

    The idea that it’s all about protein folding has already been adequately debunked at TSZ. Maybe Nick should read that, instead of cherry-picking.

    Now all of a sudden everyone has tunnel vision.

  44. 44
    Mung says:

    I’ve been debating the issues raised by the post by Rumraket at TSZ since the 22nd. Nick’s a johnny-come-lately and really has some catching up to do.

    Here’s Rumraket himself saying what his post is about:

    My post, which is a repost of something I also brought up in a thread on Larry Moran’s sandwalk blog, is about a chapter in Stephen Meyer’s book Darwin’s Doubt and what I can, if I’m being generous, only attribute to extremely shoddy scholarship.

    Nary a mention of protein folding, Nick.

  45. 45
    Mung says:

    Nick must not have received his Christmas spanking.

  46. 46
    RexTugwell says:

    One thing is for certain: Meyer, ID and UD are being dismissed. 🙂

  47. 47
    bornagain77 says:

    As briefly highlighted in post 21, as bad as the probabilities are for Darwinists to ever coherently explain the origin of new proteins by unguided material processes, that is only the tip of the iceberg as far as coherently explaining the origination of novel ‘form’ in the fossil record.

    In fact, the reductive materialistic foundation upon which neo-Darwinian evolution rests is not even in the right ballpark as to being a coherent explanation for the origination of novel ‘form’ in the fossil record.

    As Dr. Meyer puts the problem, “Genetic mutations are simply the wrong tool for the job at hand.”

    “These different sources of epigenetic information in embryonic cells pose an enormous challenge to the sufficiency of the neo-Darwinian mechanism. According to neo-Darwinism, new information, form, and structure arise from natural selection acting on random mutations arising at a very low level within the biological hierarchy—within the genetic text. Yet both body-plan formation during embryological development and major morphological innovation during the history of life depend upon a specificity of arrangement at a much higher level of the organizational hierarchy, a level that DNA alone does not determine. If DNA isn’t wholly responsible for the way an embryo develops—for body-plan morphogenesis—then DNA sequences can mutate indefinitely and still not produce a new body plan, regardless of the amount of time and the number of mutational trials available to the evolutionary process. Genetic mutations are simply the wrong tool for the job at hand.”
    Stephen Meyer – Darwin’s Doubt (p. 281)

    “In addition to the information stored in individual genes and the information present in the integrated networks of genes and proteins in dGRNs [developmental gene regulatory networks], animal forms exemplify hierarchical arrangements or layers of information-rich molecules, systems, and structures. For example, developing embryos require epigenetic information in the form of specifically arranged (a) membrane targets and patterns, (b) cytoskeletal arrays, (c) ion channels, and (d) sugar molecules on the exterior of cells (the sugar code)… Much of this information resides in the structure of the maternal egg and is inherited directly from membrane to membrane independently of DNA…
    “…This information at a higher structural level in the maternal egg helps to determine the function of both whole networks of genes and proteins (dGRNs) and individual molecules (gene products) at a lower level within a developing animal.”
    Stephen Meyer – Darwin’s Doubt – (pp. 364-365)

    Body Plans Are Not Mapped-Out by the DNA – Jonathan Wells – video
    http://www.youtube.com/watch?v=meR8Hk5q_EM

    Peer-Reviewed Paper: Development Needs Ontogenetic Information that Cannot Arise from Neo-Darwinian Mechanisms – Casey Luskin – June 2, 2014
    Excerpt: Jonathan Wells has published a new peer-reviewed scientific paper in the journal BIO-Complexity, “Membrane Patterns Carry Ontogenetic Information That Is Specified Independently of DNA.” With over 400 citations to the technical literature, this well-researched and well-documented article shows that embryogenesis depends on crucial sources of information that exist outside of the DNA.
    This ontogenetic information guides the development of an organism, but because it is derived from sources outside of the DNA, it cannot be produced by mutations in DNA. Wells concludes that because the neo-Darwinian model of evolution claims that variation is produced by DNA mutations, neo-Darwinism cannot account for the origin of epigenetic and ontogenetic information that exists outside of DNA. (Read more here:)
    http://www.evolutionnews.org/2.....86201.html

    Moreover, regulatory networks, which, as Meyer and Wells pointed out, are not able to be explained solely by reference to mutations to DNA, are turning out to be, unsurprisingly, ‘species specific’:

    Evolution by Splicing – Comparing gene transcripts from different species reveals surprising splicing diversity. – Ruth Williams – December 20, 2012
    Excerpt: A major question in vertebrate evolutionary biology is “how do physical and behavioral differences arise if we have a very similar set of genes to that of the mouse, chicken, or frog?”,,,
    A commonly discussed mechanism was variable levels of gene expression, but both Blencowe and Chris Burge,,, found that gene expression is relatively conserved among species.
    On the other hand, the papers show that most alternative splicing events differ widely between even closely related species. “The alternative splicing patterns are very different even between humans and chimpanzees,” said Blencowe.,,,
    http://www.the-scientist.com/?.....plicing%2F

    Gene Regulation Differences Between Humans, Chimpanzees Very Complex – Oct. 17, 2013
    Excerpt: Although humans and chimpanzees share,, similar genomes, previous studies have shown that the species evolved major differences in mRNA (messenger RNA) expression levels.,,,
    http://www.sciencedaily.com/re.....144632.htm

    ,,,Alternative splicing,,, may contribute to species differences – December 21, 2012
    Excerpt: After analyzing vast amounts of genetic data, the researchers found that the same genes are expressed in the same tissue types, such as liver or heart, across mammalian species. However, alternative splicing patterns—which determine the segments of those genes included or excluded—vary from species to species.,,,
    The results from the alternative splicing pattern comparison were very different. Instead of clustering by tissue, the patterns clustered mostly by species. “Different tissues from the cow look more like the other cow tissues, in terms of splicing, than they do like the corresponding tissue in mouse or rat or rhesus,” Burge says. Because splicing patterns are more specific to each species, it appears that splicing may contribute preferentially to differences between those species, Burge says,,,
    Excerpt of Abstract: To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified;
    http://phys.org/news/2012-12-e.....wires.html

    “Where (chimps and humans) really differ, and they differ by orders of magnitude, is in the genomic architecture outside the protein coding regions. They are vastly, vastly, different.,, The structural, the organization, the regulatory sequences, the hierarchy for how things are organized and used are vastly different between a chimpanzee and a human being in their genomes.”
    Raymond Bohlin (per Richard Sternberg) – 9:29 minute mark of video
    http://www.metacafe.com/watch/8593991/

    On Human Origins: Is Our Genome Full of Junk DNA? Pt 2. – Richard Sternberg PhD. Evolutionary Biology
    Excerpt: “Here’s the interesting thing, when you look at the protein coding sequences that you have in your cell what you find is that they are nearly identical to the protein coding sequences of a dog, of a carp, of a fruit fly, of a nematode. They are virtually the same and they are interchangeable. You can knock out a gene that encodes a protein for an inner ear bone in say a mouse. This has been done. And then you can take a protein that is similar to it but from a fruit fly. And fruit flies aren’t vertebrates and they certainly are not mammals., so they don’t have inner ear bones. And you can plug that gene in and guess what happens? The offspring of the mouse will have a perfectly normal inner ear bone. So you can swap out all these files. I mentioning this to you because when you hear about we are 99% similar (to chimps) it is almost all referring to those protein coding regions. When you start looking, and you start comparing different mammals. Dolphins, aardvarks, elephants, manatees, humans, chimpanzees,, it doesn’t really matter. What you find is that the protein coding sequences are very well conserved, and there is also a lot of the DNA that is not protein coding that is also highly conserved. But when you look at the chromosomes and those banding patterns, those bar codes, (mentioned at the beginning of the talk), its akin to going into the grocery store. You see a bunch of black and white lines right? You’ve seen one bar code you’ve seen them all. But those bar codes are not the same.,, Here’s an example, aardvark and human chromosomes. They look very similar at the DNA level when you take small snippets of them. (Yet) When you look at how they are arranged in a linear pattern along the chromosome they turn out to be very distinct (from one another). So when you get to the folder and the super-folder and the higher order level, that’s when you find these striking differences. And here is another example. They are now sequencing the nuclear DNA of the Atlantic bottle-nose dolphin. And when they started initially sequencing the DNA, the first thing they realized is that basically the Dolphin genome is almost wholly identical to the human genome. That is, there are a few chromosome rearrangements here and there, you line the sequences up and they fit very well. Yet no one would argue, based on a statement like that, that bottle-nose dolphins are closely related to us. Our sister species if you will. No one would presume to do that. So you would have to layer in some other presumption. But here is the point. You will see these statements throughout the literature of how common things are.,,, (Parts lists are very similar, but how the parts are used is where you will find tremendous differences)
    http://www.discovery.org/multi.....-dna-pt-2/

    Of supplemental note to Richard Sternberg’s ‘bar codes are not the same’ between species quote. It turns out that the bar code pattern that Dr. Sternberg alluded to is irreducibly complex in its organizational relation to the individual genes:

    Refereed scientific article on DNA argues for irreducible complexity – October 2, 2013
    Excerpt: This paper published online this summer is a true mind-blower showing the irreducible organizational complexity (author’s description) of DNA analog and digital information, that genes are not arbitrarily positioned on the chromosome etc.,,
    ,,,First, the digital information of individual genes (semantics) is dependent on the the intergenic regions (as we know) which is like analog information (syntax). Both types of information are co-dependent and self-referential but you can’t get syntax from semantics. As the authors state, “thus the holistic approach assumes self-referentiality (completeness of the contained information and full consistency of the different codes) as an irreducible organizational complexity of the genetic regulation system of any cell”. In short, the linear DNA sequence contains both types of information. Second, the paper links local DNA structure, to domains, to the overall chromosome configuration as a dynamic system keying off the metabolic signals of the cell. This implies that the position and organization of genes on the chromosome is not arbitrary,,,
    http://www.christianscientific.....omplexity/

  48. 48
    bornagain77 says:

    Moreover, unlike protein coding regions where there is some ‘non-catastrophic’ tolerance to random mutations, randomly mutating gene regulatory networks is found to be ‘always catastrophically bad’:

    A Listener’s Guide to the Meyer-Marshall Debate: Focus on the Origin of Information Question -Casey Luskin – December 4, 2013
    Excerpt: “There is always an observable consequence if a dGRN (developmental gene regulatory network) subcircuit is interrupted. Since these consequences are always catastrophically bad, flexibility is minimal, and since the subcircuits are all interconnected, the whole network partakes of the quality that there is only one way for things to work. And indeed the embryos of each species develop in only one way.” –
    Eric Davidson – developmental biologist
    http://www.evolutionnews.org/2.....79811.html

    Darwin or Design? – Paul Nelson at Saddleback Church – Nov. 2012 – ontogenetic depth (excellent update) – video
    Text from one of the Saddleback slides:
    1. Animal body plans are built in each generation by a stepwise process, from the fertilized egg to the many cells of the adult. The earliest stages in this process determine what follows.
    2. Thus, to change — that is, to evolve — any body plan, mutations expressed early in development must occur, be viable, and be stably transmitted to offspring.
    3. But such early-acting mutations of global effect are those least likely to be tolerated by the embryo.
    Losses of structures are the only exception to this otherwise universal generalization about animal development and evolution. Many species will tolerate phenotypic losses if their local (environmental) circumstances are favorable. Hence island or cave fauna often lose (for instance) wings or eyes.
    http://www.saddleback.com/mc/m/7ece8/

    Thus, where Darwinists most need plasticity in the genome to be viable as a theory, (i.e. developmental Gene Regulatory Networks), is the place where mutations are found to be ‘always catastrophically bad’. Yet, it is exactly in this area of the genome (i.e. regulatory networks) where substantial, ‘orders of magnitude’, differences are found between even supposedly closely related species.
    Needless to say, this is the exact opposite finding for what Darwinism would have predicted for what should have been found in the genome.
    If Darwinism were a normal science, instead of being basically the unfalsifiable ‘blind faith’ religion of atheists, this finding, by itself, should have been more than enough to falsify Darwinian claims.

    Of related note is the question of ‘what is making the billion-trillion protein molecules cohere as a single unified whole for precisely a lifetime?

    The Unbearable Wholeness of Beings – Stephen L. Talbott – 2010
    Excerpt: Virtually the same collection of molecules exists in the canine cells during the moments immediately before and after death. But after the fateful transition no one will any longer think of genes as being regulated, nor will anyone refer to normal or proper chromosome functioning. No molecules will be said to guide other molecules to specific targets, and no molecules will be carrying signals, which is just as well because there will be no structures recognizing signals. Code, information, and communication, in their biological sense, will have disappeared from the scientist’s vocabulary.
    ,,, the question, rather, is why things don’t fall completely apart — as they do, in fact, at the moment of death. What power holds off that moment — precisely for a lifetime, and not a moment longer?
    Despite the countless processes going on in the cell, and despite the fact that each process might be expected to “go its own way” according to the myriad factors impinging on it from all directions, the actual result is quite different. Rather than becoming progressively disordered in their mutual relations (as indeed happens after death, when the whole dissolves into separate fragments), the processes hold together in a larger unity.
    http://www.thenewatlantis.com/.....-of-beings

    Though I will not go into the details of quantum information in DNA and proteins, the answer to the question of ‘what is cohering the billion-trillion proteins of a human body together as a single unified whole for precisely a lifetime?’ is one that I am sure many atheistic Darwinists will, for personal reasons, find unpalatable:

    picture – What power holds off that moment — precisely for a lifetime, and not a moment longer?
    http://img.hithenews.com/image.....photo4.jpg

    Verse:

    Matthew 16:26
    What good will it be for someone to gain the whole world, yet forfeit their soul? Or what can anyone give in exchange for their soul?

  49. 49
    J-Mac says:

    I’ve just realized that the only reason why Nick Matzke hasn’t been banned here at UD is so that the honest observers can see his and Darwinist’s shamelessness.

    This is nothing new. No Darwinist can survive unless he/she has the ability to deny the obvious evidence or conclusion and move on as if nothing happen.

  50. 50
    NickMatzke_UD says:

    44
    MungDecember 26, 2015 at 2:15 pm
    I’ve been debating the issues raised by the post by Rumraket at TSZ since the 22nd. Nick’s a johnny-come-lately and really has some catching up to do.

    Here’s Rumraket himself saying what his post is about:

    My post, which is a repost of something I also brought up in a thread on Larry Moran’s sandwalk blog, is about a chapter in Stephen Meyer’s book Darwin’s Doubt and what I can, if I’m being generous, only attribute to extremely shoddy scholarship.

    Nary a mention of protein folding, Nick.

    Um, wha? Rasmussen/Rumraket says Meyer’s scholarship is shoddy because of Meyer’s uninformed claims about lots of protein folds having to originate in the Cambrian Explosion.

  51. 51
    ppolish says:

    Isn’t it about time to retire the expression “Intelligent Design”? Replace it with “Biological Fine Tuning”? More scientific, BFT.

    Anyway, Joy to the world:)
    Let Heaven & Nature sing!

    “Wait, Nature does not sing:(!”. Well if Nature isn’t singing, who/what is?

  52. 52
    Mung says:

    Yes, yes, Nick. There’s what Rumraket says his OP is about and there’s Rumraket’s OP which says what it’s about.

    Here’s another example from his OP, also quoted in the OP by VJT:

    It gets much worse, turns out Meyer is making assertions diametrically opposite to what his very very few references say. Remember what Meyer wrote above?

    “The late geneticist and evolutionary biologist Susumu Ohno noted that Cambrian animals required complex new proteins such as, for example, lysyl oxidase in order to support their stout body structures.”

    Well, much later in the same chapter, Meyer finally references Ohno:

    “Third, building new animal forms requires generating far more than just one protein of modest length. New Cambrian animals would have required proteins much longer than 150 amino acids to perform necessary, specialized functions.21”

    What is reference 21? It’s “21. Ohno

    Nary a mention of protein folds, Nick. Zero.

    And then there is the long quote from Ohno, also containing nothing about protein folds.

    Then there’s Rumraket again:

    I trust you can see the problem here. So, Meyer makes a single goddamn reference to support the claim that the Cambrian explosion required a lot of innovation of new proteins, folds, cell-types and so on.


    1. New Proteins
    2. New Folds
    3. New Cell Types
    4. and so on

    But really, it’s all about just the folds. Hah. Good one.

  53. 53
    Mung says:

    ppolish, Nature does sing.

  54. 54
    groovamos says:

    Matzke: biologists are so dismissive of Meyer, ID, and UD.

    Well now that would seem to conform with quoted biologist being dismissive of UD and proving it by staying away from the site wouldn’t it?

    The guy is laughable, just can keep his hands to himself, and continue with his business. Could it be he is alarmed at ID now spreading to other countries, and is a little bit desperate?

  55. 55
    ppolish says:

    Going from a dead rock to a live 5 octave voice is unnatural Mung. That is not supposed to happen. Ever. But yes, Nature has done it. Not unguided btw. Not even close.
    https://m.youtube.com/watch?v=dXlLXeK3ZiY

  56. 56
    Andre says:

    I am trying to give Nick Matzke the benefit of doubt but here is the thing…Darwin himself saw issues with the Cambrian. Did Nick Matzke or any of the Darwin Disciples prove Charles Darwin wrong yet?

  57. 57
    Mung says:

    I give Nick the benefit of the doubt too. His argument goes something like this.

    Rumraket says his OP is about protein folds.
    Rumraket wrote his OP, therefore he ought to know what it’s about.
    Therefore, it’s about protein folds.
    And ID’ists are dumb and dumber.

    Unfortunately for Nick, anyone can read the OP and see for themselves that it’s about more than just protein folds appearing in the Cambrian.

    Not only that, anyone can read the thread itself, Nick included, and see how it has been pointed out that Rumraket has misread or misunderstood Meyer’s argument.

    Now it’s very unlikely that Nick will want to repeat the history of that thread here at UD, because he’d look like a fool. Better to pretend that it’s only about protein folding.

    Yeah, I give him the benefit of the doubt too.

  58. 58
    Mung says:

    Of all the differences between ourselves and our amoeba-like ancestors a billion years ago, one is paramount: we have bodies. Instead of a single cell, we are made of trillions. This vast collection isn’t just a bag of identical copies, but a menagerie of dozens of types of cells, organized into hundreds of body parts [some are organs] from spleens to eyelashes to skeletons to brains. And most remarkable of all, each of our bodies is built out of a single original cell. As that cell multiplies into an embryo, genes begin producing proteins that control its development.

    – Carl Zimmer. Evolution.

    It is absolutely mind-boggling to think that what everyone ought to know is held against Meyer because he failed to cite all his sources for all his claims.

    Oh, wait. It’s not about that!

  59. 59
    Mung says:

    Most animals, including us, use a standard tool kit of body-building genes. It contains tools for marking off the coordinates of an animals body – front and back, left and right, head and tail. It also contains a set of genes that control the development of entire organs such as eyes and limbs. The tool kit is remarkably unchanged from one species to another…

    Judging from the fossil record, this tool kit must have gradually evolved in the millions of years that preceded that Cambrian explosion.

    – Carl Zimmer. Evolution.

    I just love the “toolkit” and “tools for” language. Warms the heart of a designer.

    Must have evolved in the millions of years before the Cambrian? Why?

    What are some of the remarkable features of this “toolkit” that existed before the animals in the Cambrian came along?

    Nick? Anyone?

  60. 60
    groovamos says:

    RexT: One thing is for certain: Meyer, ID and UD are being dismissed.

    Yes true, thanks to the idea that stupid nature could accidentally come up with a spectacular work of art, a stunning symphony, or the invention of mathematics. Cuz see, stupid nature has this principle it must live by called survival, which requires spectacular works of art, stunning symphonies, and the invention and application of say, the Jacobian determinant. Plain as day, can’t everybody see it? Except we’re left with where did the principle of survival get invented, maybe stupid nature itself did so which would mean that the principle itself would have to be stupid, and therefore not have any way of motivating itself to attain the hegemony required of itself in order to write a beautiful symphony sometime to maintain itself i.e. survive, and then prove it isn’t stupid after all. But rather, possibly intelligent.

  61. 61
    vjtorley says:

    Hi Nick Matzke,

    Thank you for your posts. It’s perfectly consistent for Dr. Meyer to argue that (a) judging from the fossil evidence, the Cambrian explosion appears to have happened very quickly, over a few million years, but that (b) even if the underlying events at the biochemical level and the genetic level occurred more slowly, over a few billion years, there still wouldn’t be enough time available.

    You take issue with Meyer’s statement:

    “In some cases new proteins, while functionally new, would perform their different functions with essentially the same fold or tertiary structure as earlier proteins. But more often, proteins capable of performing new functions require new folds to perform these functions. That means that explosions of new life-forms must have involved bursts of new protein folds as well.”

    Note that Meyer himself admits that in some cases, new proteins can perform a new function “with essentially the same fold or tertiary structure as earlier proteins.” What he contends is that it’s more common, however, for proteins capable of performing new functions to require new folds to perform these functions. All you’ve said, in response to Meyer, is that “[y]ou can have many different kinds of proteins that all draw from the same folds.” That in no way invalidates Meyer’s point.

    If you think Dr. Meyer’s claim is factually mistaken, then where’s your documentation to back it up?

  62. 62
    Mung says:

    Meyer’s argument regarding protein folds depends on the work of Douglas Axe. There can be no doubt about this upon any fair reading of chapter 10 of Darwins Doubt.

    Further, it has been extensively documented at TSZ that the time scale involved is the entire history of life. Again, there can be no doubt about this upon any fair reading of chapter 10 of Darwins Doubt.

    It was also explained over at TSZ that the claim that there wasn’t enough time in the Cambrian is merely a corollary of the overall conclusion of the argument.

    Nick is probably unaware of any of this.

  63. 63
    YouThinkSo says:

    Evolution is a fascinating thing indeed. All sorts of things can evolve. For instance, something very fascinating evolved, something involving text, something that eventually showed up within the Bible. I can’t explain exactly how this evolved. A crystal clear repetitive and logical pattern appears over and over within the Bible. But, since it is of no immediate financial benefit to anyone, nor any other immediate benefit that I can think of, it therefore is of no interest. If insane, meaning if you are interested in the non-interesting, go to http://goo.gl/38qhp and click on the flashing words “Watch/Listen”.

  64. 64
    gpuccio says:

    To all:

    The following paper, kindly linked by Dionisio in another thread, is probably of some relevance for the discussion here:

    Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

    http://genome.cshlp.org/conten.....1.full.pdf

    Abstract:
    Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.

  65. 65
    Virgil Cain says:

    Nick Matzke:

    Rasmussen/Rumraket says Meyer’s scholarship is shoddy because of Meyer’s uninformed claims about lots of protein folds having to originate in the Cambrian Explosion.

    No one knows what was required, Nick. Meyer could be right and no one can show that he is wrong. And there isn’t any known mechanism to account for the diversity observed. You lose.

  66. 66
    vjtorley says:

    Hi everyone,

    May I note for the record that protein folds are mentioned in only a single sentence of Nick Matzke’s review of Dr. Meyer’s book, Darwin’s Doubt. The relevant sentence reads: “The basic protein domains mostly originated very far back in evolutionary history, where things like ultrahigh population sizes help out, as well as the fact that there are probably a fairly limited number of protein domains, and the fact that point mutations and rearrangements can, on occasion, produce new or modified protein folds, in some cases without having much effect on enzymatic activity.” However, no references are given to support this claim – the very failure that Mikkel “Rumraket” Rasmussen upbraids Dr. Meyer for.

    By the way, David Berlinski and Tyler Hampton have written a devastating reply to Matzke’s review of Dr. Meyer’s book. The reply is titled, Hopeless Matzke.

  67. 67
    RexTugwell says:

    @vjt, FWIW I had the same thought this morning. Matzke also gave short shrift (one sentence) to developmental biology in his review. Alas, when you’re acting like a second grader and jockeying to be first in line (in this case the first to “review” Darwin’s Doubt) shortcuts are taken and details are overlooked.

  68. 68
    Barry Arrington says:

    Nick,

    Your “review” came out 24 hours after the book was published. When are you going to admit that it is impossible to read a book and write a 9,000 word review of the book in 24 hours? What really happened Nick (he asked as if he did not already know the answer)?

  69. 69
    NickMatzke_UD says:

    Note that Meyer himself admits that in some cases, new proteins can perform a new function “with essentially the same fold or tertiary structure as earlier proteins.” What he contends is that it’s more common, however, for proteins capable of performing new functions to require new folds to perform these functions. All you’ve said, in response to Meyer, is that “[y]ou can have many different kinds of proteins that all draw from the same folds.” That in no way invalidates Meyer’s point.

    If you think Dr. Meyer’s claim is factually mistaken, then where’s your documentation to back it up?

    I can’t believe you haven’t gotten it yet. It’s very simple. We have genomes from many bilaterian phyla. We can look at what genes/proteins they have, and what protein folds they have. And as far as we can tell, they all have basically the same collection of protein folds (and, mostly, the same genes/proteins too, although there are many duplications and rearrangements, so it depends what you mean here).

    Therefore, whatever new functions, new developmental biology, new “information”, etc., that originated with the Cambrian Explosion phyla, did not actually require lots of new protein folds. Because they don’t actually have lots of new protein folds.

    This is known to every serious student of the question, but apparently not to Meyer and his followers. That, or it’s ignored because they desperately want to somehow make Axe relevant to the Cambrian Explosion.

  70. 70
    NickMatzke_UD says:

    66
    vjtorleyDecember 27, 2015 at 9:35 am
    Hi everyone,

    May I note for the record that protein folds are mentioned in only a single sentence of Nick Matzke’s review of Dr. Meyer’s book, Darwin’s Doubt. The relevant sentence reads: “The basic protein domains mostly originated very far back in evolutionary history, where things like ultrahigh population sizes help out, as well as the fact that there are probably a fairly limited number of protein domains, and the fact that point mutations and rearrangements can, on occasion, produce new or modified protein folds, in some cases without having much effect on enzymatic activity.” However, no references are given to support this claim – the very failure that Mikkel “Rumraket” Rasmussen upbraids Dr. Meyer for.

    Well, I was writing an off-the-cuff blogpost in a limited amount of time, Meyer and allies were claiming that Meyer’s book deserved attention as a revolutionary new scientific work that was overthrowing a good chunk of modern mainstream biology.

    But, since you asked, I was referring to the work of people like Nick Grishin:

    Evolution of protein structures and functions
    LN Kinch, NV Grishin – Current opinion in structural biology, 2002

    Within the ever-expanding repertoire of known protein sequences and structures, many examples of evolving three-dimensional structures are emerging that illustrate the plasticity and robustness of protein folds. The mechanisms by which protein folds change often include the fusion of duplicated domains, followed by divergence through mutation. Such changes reflect both the stability of protein folds and the requirements of protein function.

    Fold change in evolution of protein structures
    NV Grishin – Journal of structural biology, 2001

    Typically, protein spatial structures are more conserved in evolution than amino acid sequences. However, the recent explosion of sequence and structure information accompanied by the development of powerful computational methods led to the accumulation of examples of homologous proteins with globally distinct structures. Significant sequence conservation, local structural resemblance, and functional similarity strongly indicate evolutionary relationships between these proteins despite pronounced structural differences at the fold level. Several mechanisms such as insertions/deletions/substitutions, circular permutations, and rearrangements in ?-sheet topologies account for the majority of detected structural irregularities. The existence of evolutionarily related proteins that possess different folds brings new challenges to the homology modeling techniques and the structure classification strategies and offers new opportunities for protein design in experimental studies.

    Discrete–continuous duality of protein structure space
    RI Sadreyev, BH Kim, NV Grishin – Current opinion in structural biology, 2009

    Recently, the nature of protein structure space has been widely discussed in the literature. The traditional discrete view of protein universe as a set of separate folds has been criticized in the light of growing evidence that almost any arrangement of secondary structures is possible and the whole protein space can be traversed through a path of similar structures. Here we argue that the discrete and continuous descriptions are not mutually exclusive, but complementary: the space is largely discrete in evolutionary sense, but continuous geometrically when purely structural similarities are quantified. Evolutionary connections are mainly confined to separate structural prototypes corresponding to folds as islands of structural stability, with few remaining traceable links between the islands. However, for a geometric similarity measure, it is usually possible to find a reasonable cutoff that yields paths connecting any two structures through intermediates.

    What? Reading Meyer and Axe didn’t inform you of any of this?

    I saw Nick Grishin speak at SMBE 2014:
    https://twitter.com/NickJMatzke/status/476357446160502784

    My main impression from seeing his more recent work is that the evolution of protein fold change is a whole subfield with more people involved than there are active ID authors. Yet you could read the ID literature and never even know this existed.

    By the way, David Berlinski and Tyler Hampton have written a devastating reply to Matzke’s review of Dr. Meyer’s book. The reply is titled, Hopeless Matzke.

    Heh. That review is ridiculous. If you fight through Berlinski’s pointlessly purple prose, you end up realizing that Berlinski concedes that, yes, natural evolutionary processes *can* produce new genes with new functions. This undermines Meyer’s fundamental argument that only intelligence can produce new information, as well as shooting down a whole more specific section of Meyer’s book where Meyer claims that the extensive evolutionary literature on the origin of new genes is all doubtful.

  71. 71
    Andre says:

    Nick

    Nice litrature bluffing again. As soon as you give us in the lab evidence that new genes just poof into existence be sure to drop by and deliver the news. Until then you may huff and puff all you like.

    For those wondering what Nick is all excited about his “proof” is good old designed programs doing directed simulations and is in no way an indication that undirected evolution is responsible because Nick, tbe upstanding and honest person that he is, won’t tell you that it does not fit in with his agenda of being a book burner.

  72. 72
    CharlieM says:

    The living world as we know it would not exist without features that are put in place to allow future events to come to fruition. for example birds build nests to house the eggs which are yet to be laid. The genome of an animal contains the information to build the tissues of the adult form well before differentiation takes place.

    So if the protein folds necessary to construct the diversity of forms known to have appeared during the Cambrian explosion were in place before that event occurred then that would be consistent with the preparative nature of unfolding life. Growth and expansion precede differentiation and diversity of form.

    Life had prepared for the sudden appearance of the Cambrian forms just as the organs of an individual animal were prepared in the blastula.

  73. 73
    Mung says:

    Without those new Cambrian genes, we might still be like the lancelets, our tiny brainless heads still swaying in the tides.

    – Carl Zimmer. Evolution p. 126

    Don’t know why Nick made me think of that.

  74. 74
    Mung says:

    The earliest animals were extremely simple, with only a handful of different kinds of cells, assembled by relatively few developmental genes. By the end of the Cambrian explosion, their descendants had evolved many different types of cells and used a complicated network of interacting genes to build their bodies.

    – Carl Zimmer. Evolution p. 128

  75. 75
    Virgil Cain says:

    Nick Matzke:

    If you fight through Berlinski’s pointlessly purple prose, you end up realizing that Berlinski concedes that, yes, natural evolutionary processes *can* produce new genes with new functions.

    That is your interpretation. However there isn’t any evidence for such a thing.

  76. 76
    Arthur Hunt says:

    Nice litrature bluffing again. As soon as you give us in the lab evidence that new genes just poof into existence be sure to drop by and deliver the news. Until then you may huff and puff all you like.

    I believe Dembski as much as stated that new protein-coding genes can poof into existence. IIRC, check out pp.218–219 of No Free Lunch.

    Want to (re)discover one on your own? The route taken to identify the so-called ecf mutant in E. coli in the 1970’s is pretty intriguing and suggestive. And the phenotype is quite in line with the gene he talks about in NFL. Maybe some enterprising IDer can see if the Discovery Institute would pay for, say, a couple of months of lab work and sequencing.

  77. 77
    bornagain77 says:

    The interesting thing about Darwinists claiming that genes/proteins can randomly ‘poof’ into existence is that no one can seem to catch this random ‘poofing’ in action.

    First off, it is hard to find anything that is truly ‘random’ in its action in the cell as is presupposed in Darwinian thought:

    “It is difficult (if not impossible) to find a genome change operator that is truly random in its action within the DNA of the cell where it works. All careful studies of mutagenesis find statistically significant non-random patterns”
    James Shapiro – Evolution: A View From The 21st Century – (Page 82)

    In fact, the genome is best viewed as a read/write memory instead of a read only memory as is viewed in Darwinian thought:

    How life changes itself: the Read-Write (RW) genome. – 2013
    Excerpt: Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences.
    http://www.ncbi.nlm.nih.gov/pubmed/23876611

    Secondly, unguided material processes are far more likely to break something in the cell to gain a short term fitness advantage that they are ever likely to build up functional complexity/information for future use:

    “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain – Michael Behe – December 2010
    Excerpt: In its most recent issue The Quarterly Review of Biology has published a review by myself of laboratory evolution experiments of microbes going back four decades.,,, The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.,,, I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain.
    http://behe.uncommondescent.co.....evolution/

    Moreover, in the four decades worth of lab work that Dr. Behe surveyed, there was not even any evidence of just one novel gene being created. Instead, all gain of function mutations, as far as I could tell, involved ‘compensatory mutations’ that compensated for a gene that was deleted.

    Thirdly, humans trying to intelligently design proteins that outperform what is already found in life fall far short of what is already found in life. To believe unguided material processes can out engineer our best molecular engineers of today is logically absurd to a very high degree.

    Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for the Creator – Fazale Rana
    Excerpt of Review: ‘Another interesting section of Creating Life in the Lab is one on artificial enzymes. Biological enzymes catalyze chemical reactions, often increasing the spontaneous reaction rate by a billion times or more. Scientists have set out to produce artificial enzymes that catalyze chemical reactions not used in biological organisms. Comparing the structure of biological enzymes, scientists used super-computers to calculate the sequences of amino acids in their enzymes that might catalyze the reaction they were interested in. After testing dozens of candidates,, the best ones were chosen and subjected to “in vitro evolution,” which increased the reaction rate up to 200-fold. Despite all this “intelligent design,” the artificial enzymes were 10,000 to 1,000,000,000 times less efficient than their biological counterparts. Dr. Rana asks the question, “is it reasonable to think that undirected evolutionary processes routinely accomplished this task?”
    http://www.amazon.com/gp/product/0801072093

    Dr. Fuz Rana, at the 41:30 minute mark of the following video, speaks on the tremendous effort that went into building the preceding protein:

    Science – Fuz Rana – Unbelievable? Conference 2013 – video
    http://www.youtube.com/watch?v.....38;index=8

    Computer-designed proteins programmed to disarm variety of flu viruses – June 1, 2012
    Excerpt: The research efforts, akin to docking a space station but on a molecular level, are made possible by computers that can describe the landscapes of forces involved on the submicroscopic scale.,, These maps were used to reprogram the design to achieve a more precise interaction between the inhibitor protein and the virus molecule. It also enabled the scientists, they said, “to leapfrog over bottlenecks” to improve the activity of the binder.
    http://phys.org/news/2012-06-c.....ruses.html

    Exactly how is it possible for unguided material processes, without intelligent foresight, to ‘leapfrog over bottlenecks’ to improve the activity of a binder?

    “I build molecules for a living, I can’t begin to tell you how difficult that job is. I stand in awe of God because of what he has done through his creation. Only a rookie who knows nothing about science would say science takes away from faith. If you really study science, it will bring you closer to God.”
    James Tour – one of the leading nano-tech engineers in the world – Strobel, Lee (2000), The Case For Faith, p. 111

    Dr. James Tour, who, in my honest opinion, currently builds the most sophisticated man-made molecular machines in the world, will buy lunch for anyone who can explain to him exactly how Darwinian evolution works:

    Does Science Make Faith Obsolete? James Tour – video – March 9, 2015 (talk given February 18, 2015 – 30:20 minute mark – he publicly asks Darwinists to explain macro-evolution to him)
    https://www.youtube.com/watch?feature=player_detailpage&v=CB3ZmLatcUI#t=1827

    After commenting on the failure of ANY atheist to ever respond to his request for lunch for 8 or 10 years in order to explain macro-evolution to him, Dr Tour comments:

    “One graduate student from Berkeley, (i.e. Matzke), said that he would come if he had a ticket so somebody said “I’ll buy you the ticket”, but then he said, “Well, I’m not going to go because Tour doesn’t want it recorded.” The reason I didn’t want it recorded is because I did not want one-ups-man-ship.
    I said ‘I’ll buy you lunch, just explain it to me’.
    And then the guy said he would send me some articles on evolution of a complex system from a molecular perspective and I am still waiting. That’s over one year ago he was suppose to send them to me. They don’t exist.”
    – James Tour – 35:22 minute mark of the video
    https://youtu.be/CB3ZmLatcUI?t=2122

    I guess that Dr. Matzke thought it wise not to try his usual literature bluff on a leading nano-tech engineer in the world.

    Given Dr. Tour’s prestige and expertise, it is one literature bluff that certainly could have backfired on Matzke big time

    A short history of Matzke’s literature bluffing – Nov. 2015
    http://www.uncommondescent.com.....ent-589458

  78. 78
    vjtorley says:

    Hi Nick Matzke,

    I’m afraid I don’t buy your excuse for mentioning protein folds just once in your review of Darwin’s Doubt. You state that you were pressed for time. OK, but eight days later, when you responded to Casey Luskin’s rebuttal of your review, you had much more time at your disposal. Why, then, does the word “protein” not appear even once in your reply to Luskin? And why doesn’t the word “fold” appear either? Strange.

    I can only conclude that at the time when you penned your reviews, you didn’t know enough about proteins or protein folds to rebut Dr. Meyer’s argument concerning the rarity of functional proteins in protein space, and about the need for thousands of different kinds of protein folds in order to account for the diversity of animal life. However, you’ve done a bit of reading since then, and now you’re trying to pretend that you’ve known all along that Meyer was wrong on this point. Am I right?

    “Oh yeah? Where’s your evidence?” I hear you ask. Happy to oblige. I did a quick Google search on the terms “Nick Matzke” and “Grishin”, and the earliest document I could find where your names were associated was comment of yours in an article you wrote on Panda’s Thumb, titled, “Game over for antievolutionary No Free Lunch argument.” The date of the comment: December 5, 2015. The article itself was written on December 4, 2015 – just a little over three weeks ago. As far as I can tell, that’s your earliest mention of Grishin’s work on proteins. I also searched on Google Scholar for anything containing both your names, but came up blank.

    Here’s what you said in your comment on December 5, 2015:

    Protein folds are the emergency backup-backup-backup argument after claims about specified complexity, “evolution can’t produce new information”, “evolution can’t produce new genes”, etc., have been debunked and tacitly abandoned. Most protein folds are very widespread (shared not just among animals but across eukaryotes and often prokaryotes also) so their origins must be very ancient – the argument that Meyer, Luskin etc. have been making lately, which is that a whole bunch of new protein folds had to originate in the Cambrian Explosion, is just ignorant crazypants.

    So the origin of protein folds will typically be rarer and more ancient than almost anything short of the origin of life itself, and thus harder to study. But all that said, there is nevertheless a lot that can be said. In fact, there are known cases where tiny amounts of mutation can convert one protein fold into another one.

    Look up: Nick Grishin.
    https://scholar.google.com.au/scholar?q=Nick+Grishin%2C+protein+folds&btnG=&hl=en&as_sdt=0%2C5

    Michael Buratovich (2015). Leaving the Fold. “Darwin’s Doubt and the Evolution of Protein Folds.” Reports of the National Center for Science Education Vol 35, No 5 (2015)
    http://reports.ncse.com/index......ew/379/751

    I note that your first link takes us to a Google page with the search parameters “Nick Grishin, protein folds”. That’s rather sloppy, Nick. Your second link is much more substantive: it takes the reader to an article that actually addresses Dr. Axe’s and Dr. Meyer’s arguments. However, I was totally unimpressed with Buratovich’s response to Axe’s arguments on the rarity of functional proteins in protein space.

    First, he takes issue with Meyer’s use of Axe’s lower estimate of 1 in 10^77, saying that he neglected to mention an upper bound of 1 in 10^53. In fact, Meyer’s book, Signature in the Cell, cites both upper and lower estimates, and argues that since the simplest living cells require about 250 different proteins, it doesn’t make much practical difference we use: we still obtain a vanishingly low probability. I might add that Taylor et al. have acknowledged that “Even a library with the mass of the Earth itself — 5.98 × 10^27 g — would comprise at most 3.3 × 10^47 different sequences, or a miniscule (sic) fraction of such diversity.”

    Second, Buratovich says that the numbers aren’t that bad for proteins shorter than 150 amino acids, and there are plenty of those in Nature. True, but what he omits to mention is that all living things require at least some proteins which are 150 amino acids long. What’s more, as Dr. Cornelius Hunter has previously pointed out, there are no good scientific grounds for thinking that life-forms based on shorter, simpler proteins could have existed in the beginning, giving rise to more advanced life-forms requiring larger, more complex ones later on. As he puts it: “The larger ones appear to be needed, and there are not obvious gradual pathways to forming them.”

    Third, Buratovich argues that the estimate refers only to the proportion of amino acids that will perform a specified function, and that it is not (his italics) the estimation of the (probability of the) evolution of a protein fold. That’s just flat out false. He’s mis-read Axe’s argument: basically, he’s accusing Axe (or Meyer) of committing Hoyle’s fallacy. If it were that simple, Meyer and Axe would have been utterly discredited long ago.

    Fourth, Buratovich states that the proportion of amino acid sequences that are functional depends on the way you define functionality, and that if you define it in a more relaxed way, the true proportion is about 1 in 5×10^23. But the protein they used was a short one (95 amino acids). And as Dr. Cornelius Hunter wrote to me in a personal communication back in 2014:

    Taylor, et. al. deals with a simple, helix only, protein (homodimeric AroQ), biased the sequence toward helix forming amino acids and sequence patterns, did not fully randomize the sequence but only randomized regions, and is vague about how they arrive at their 10^24 tries required. Even if their calculation of 10^24 is reasonable, you’re dealing with a pretty simple protein… AroQ is toward the simple end of the spectrum… And finally there are several studies on slightly more complex, challenging proteins, all of which come in at around 10^60 – 10^80 attempts required.”

    I refuted most of Buratovich’s silly arguments in section 11 of my June 2014 post, The dirty dozen: Twelve fallacies evolutionists make when arguing about the origin of life. I note that some of them reference articles dating back to 2001. That’s ancient history.

    As for protein folds: I can’t really comment here, except to say that: (i) even if all animals share the same set of protein folds, the question we need to answer in order to ascertain how old they are is whether closely related organisms (e.g. fungi) share them as well; (ii) even if it should turn out that these folds go back to the dawn of life, the point is that there are still thousands of them, and the question we need to answer is: how did unguided processes manage to locate these “needles in a haystack”? Until you can address those questions, Nick, you can’t expect to be taken seriously.

  79. 79
    Bob O'H says:

    vjtorley – There’s evidence that Nick M. knew of Nick G. in June 2014.

  80. 80
    NickMatzke_UD says:

    Wow, that’s a really long way of avoiding admitting error in your Opening Post, VJ Torley. Meyer asserted the Cambrian explosion required many new protein folds. This is clearly false and has been disproven, and Meyer definitely should have known this, and his defenders should have also (Most of the folds are indeed shared with fungi — but also closer outgroups — choanoflagellates, sponges, etc.) Until you admit Meyer made a mistake there, there is little point in continuing. Start a new thread if you want to talk about new topics, and everyone can make up their own minds about whether to discuss those.

    PS: Your Google skills need work. I’ve known about Grishin’s work for a long time. Whether or not I ever had occasion to reference it is a different question – I don’t think I’ve ever written an extended discussion of the origin of protein folds. But, as it happens, I used to save potentially useful references on CiteUlike, and lo and behold: http://www.citeulike.org/user/matzke/tag/evolution . That’s 2 Grishin articles and several others on the same topic. In April 2005.

  81. 81
    bornagain77 says:

    I would not be too quick to presuppose that no new protein folds were required for the Cambrian explosion:

    It has recently been found that unique ORFan proteins are a far bigger problem than Darwinists would have preferred to believe:

    Unexpected features of the dark proteome – Oct. 2015
    Excerpt: Nearly half of the dark proteome comprised dark proteins, in which the entire sequence lacked similarity to any known structure. Dark proteins fulfill a wide variety of functions,,,
    We deliberately chose this stringent definition of “darkness,” so we can be confident that the dark proteome has completely unknown structure.,,,
    ,,,in eukaryotes and viruses, about half (44–54%) of the proteome was dark (Fig. 1B). Of the total dark proteome, nearly half (34–52%) comprised dark proteins.
    We repeated the above analysis using an even more stringent definition for darkness—combining PMP (2) and Aquaria (SI Methods) — but this had little effect (Fig. S1).,,,
    Lower Evolutionary Reuse.
    For each protein, we calculated how frequently any part of its sequence has been reused across all other known proteins (SI Methods). Dark proteins were reused much less frequently than nondark proteins (Fig. 4 C and Fig. S8), suggesting that dark proteins may be newly evolved proteins or rare proteins adapted to specific functional niches. This result was partly expected, given how darkness was defined and given the progress of structural genomics in targeting large protein families with unknown structure (8). Low evolutionary reuse also partly explains why dark proteins have few known interactions (Fig. 4 B and Fig. S8), because many interactions are inferred by homology (33).
    http://www.pnas.org/content/ea.....2.full.pdf

    The Dark Proteome and Dark Evolution – Evolution Did It – Cornelius Hunter – Nov. 23, 2015
    Excerpt: “Thus, our results suggest that many of the uncharacterized orphan sequences … are indeed real proteins.”
    http://darwins-god.blogspot.co.....ution.html

    Moreover, ‘context dependency’, where quantum information is shown to physically reside along the entire protein chain, greatly exasperates the search problem for unguided Darwinian processes.

    Quantum criticality in a wide range of important biomolecules
    Excerpt: “Most of the molecules taking part actively in biochemical processes are tuned exactly to the transition point and are critical conductors,” they say.
    That’s a discovery that is as important as it is unexpected. “These findings suggest an entirely new and universal mechanism of conductance in biology very different from the one used in electrical circuits.”
    The permutations of possible energy levels of biomolecules is huge so the possibility of finding even one that is in the quantum critical state by accident is mind-bogglingly small and, to all intents and purposes, impossible.,, of the order of 10^-50 of possible small biomolecules and even less for proteins,”,,,
    “what exactly is the advantage that criticality confers?”
    https://medium.com/the-physics-arxiv-blog/the-origin-of-life-and-the-hidden-role-of-quantum-criticality-ca4707924552

    Proteins ‘ring like bells’ – June 2014
    As far back as 1948, Erwin Schrödinger—the inventor of modern quantum mechanics—published the book “What is life?”
    In it, he suggested that quantum mechanics and coherent ringing might be at the basis of all biochemical reactions. At the time, this idea never found wide acceptance because it was generally assumed that vibrations in protein molecules would be too rapidly damped.
    Now, scientists at the University of Glasgow have proven he was on the right track after all.
    Using modern laser spectroscopy, the scientists have been able to measure the vibrational spectrum of the enzyme lysozyme, a protein that fights off bacteria. They discovered that this enzyme rings like a bell with a frequency of a few terahertz or a million-million hertz. Most remarkably, the ringing involves the entire protein, meaning the ringing motion could be responsible for the transfer of energy across proteins.
    The experiments show that the ringing motion lasts for only a picosecond or one millionth of a millionth of a second. Biochemical reactions take place on a picosecond timescale and,,, (are) optimised enzymes to ring for just the right amount of time. Any shorter, and biochemical reactions would become inefficient as energy is drained from the system too quickly. Any longer and the enzyme would simple oscillate forever: react, unreact, react, unreact, etc. The picosecond ringing time is just perfect for the most efficient reaction.
    These tiny motions enable proteins to morph quickly so they can readily bind with other molecules, a process that is necessary for life to perform critical biological functions like absorbing oxygen and repairing cells.,,,
    Klaas Wynne, Chair in Chemical Physics at the University of Glasgow said: “This research shows us that proteins have mechanical properties that are highly unexpected and geared towards maximising efficiency.”
    http://www.gla.ac.uk/news/headline_334344_en.html

    Proteins with cruise control provide new perspective:
    Excerpt: “A mathematical analysis of the experiments showed that the proteins themselves acted to correct any imbalance imposed on them through artificial mutations and restored the chain to working order.”
    http://www.princeton.edu/main/...../60/95O56/

    (A Reply To PZ Myers) Estimating the Probability of Functional Biological Proteins? Kirk Durston , Ph.D. Biophysics – 2012
    Excerpt (Page 4): The Probabilities Get Worse
    This measure of functional information (for the RecA protein) is good as a first pass estimate, but the situation is actually far worse for an evolutionary search. In the method described above and as noted in our paper, each site in an amino acid protein sequence is assumed to be independent of all other sites in the sequence. In reality, we know that this is not the case. There are numerous sites in the sequence that are mutually interdependent, (i.e. context dependent), with other sites somewhere else in the sequence. A more recent paper shows how these interdependencies can be located within multiple sequence alignments.[6] These interdependencies greatly reduce the number of possible functional protein sequences by many orders of magnitude which, in turn, reduce the probabilities by many orders of magnitude as well. In other words, the numbers we obtained for RecA above are exceedingly generous; the actual situation is far worse for an evolutionary search.
    http://powertochange.com/wp-co.....Myers_.pdf

    “Why Proteins Aren’t Easily Recombined, Part 2” – Ann Gauger – May 2012
    Excerpt: “So we have context-dependent effects on protein function at the level of primary sequence, secondary structure, and tertiary (domain-level) structure. This does not bode well for successful, random recombination of bits of sequence into functional, stable protein folds, or even for domain-level recombinations where significant interaction is required.”
    http://www.biologicinstitute.o.....ned-part-2

    Explaining Innovation – Ann Gauger – January 20, 2015
    Excerpt: Even though the two enzymes (Kbl2 and BioF2) we worked with look alike, the way they are put together is distinct. The particular amino acids that cause them each to fold into the same structure are unique in sequence and holistic in their interactions. Each requires high-level, top-down design.
    As we discuss in our recent paper:
    “It may be that our prior attempts to convert Kbl2 to perform the function of BioF2 failed not because we made the wrong alterations but rather because it is misguided even to think of this as an exercise in alteration.
    … They use similar structures not because they are both adjusted versions of some older enzyme, but instead because the purposes they serve happen to call for similar structures. As we found in this work, it is not that Kbl has amino acid residues that are incompatible with the function of BioF2, but rather that Kbl2 is comprehensively suited to one function, while BioF2 is comprehensively suited to another.”
    ,,, Kbl2 and BioF2 represent two distinct ideas or concepts requiring holistic design.
    http://www.evolutionnews.org/2.....92861.html

  82. 82
    Virgil Cain says:

    Nick Matzke:

    Meyer asserted the Cambrian explosion required many new protein folds. This is clearly false and has been disproven,

    Except it hasn’t been disproven as no one knows what is required to account for the diversity observed.

  83. 83
    vjtorley says:

    Hi Nick Matzke,

    You write:

    I’ve known about Grishin’s work for a long time. Whether or not I ever had occasion to reference it is a different question – I don’t think I’ve ever written an extended discussion of the origin of protein folds. But, as it happens, I used to save potentially useful references on CiteUlike, and lo and behold: http://www.citeulike.org/user/matzke/tag/evolution . That’s 2 Grishin articles and several others on the same topic. In April 2005.

    You did indeed save two articles by Grishin in 2005 (under the name “matzke” rather than “Nick Matzke,” which is why my Google search never picked it up), but you didn’t use them for a long time afterwards. I might add that the articles by Grishin which you saved were written in 2001 and 2002 – i.e. at least two years before the publication of Dr. Douglas Axe’s paper, “Estimating the prevalence of protein sequences adopting functional enzyme folds” (Journal of Molecular Biology, 2004 Aug; 341(5):1295-315). Neither of the papers you saved even attempts to estimate the antiquity of the various protein folds found in animals – in fact, neither paper even mentions animals as such (Metazoa). So the relevance of these articles to Intelligent Design or to Dr. Meyer’s book, Darwin’s Doubt, is highly debatable.

    From what I can tell (h/t Bob O’H), you never mentioned Grishin’s work in your posts until June 2014 – and that was in a very brief Twitter post.

    You also write:

    Meyer asserted the Cambrian explosion required many new protein folds. This is clearly false and has been disproven, and Meyer definitely should have known this, and his defenders should have also (Most of the folds are indeed shared with fungi — but also closer outgroups — choanoflagellates, sponges, etc.) Until you admit Meyer made a mistake there, there is little point in continuing.

    I really think you’re being a bit rude to Dr. Meyer here. Take a look at his Acknowledgments page (p. 414), where he states: “I’d also like to acknowledge the two anonymous biologists and two paleontologists who gave such careful attention to improving the scientific rigor and accuracy of the manuscript during the peer-review process.” If there are any scientific mistakes in Meyer’s book, it’s these guys who should take the fall for it, not Meyer. He did, after all, do his level best to ensure that his book from free from mistakes. He is, as he states, “not a biologist, but a philosopher of biology.”

    You write that most of the protein folds found in animals are indeed shared with fungi. Since you’re a biologist working in the field, I’ll take your word for it, although I still have a question as to how scientists determine that fold A and fold B are in fact the same fold: is “sameness” a clear-cut term, in this context, or does “the same” just mean highly similar?

    Granting that the protein folds found in animals are more ancient than animals themselves, it would appear that the protein folds shared by animals and fungi go back about 1,300 million years, since that’s the time when timetree.org estimates that animals and fungi diverged. (Animals and plants diverged about 200 million years earlier, but you do not claim that plants possess these protein folds too.) However, the actual proteins that are used by the various phyla of animals are likely to be far more recent, and may well go back no further than the Ediacaran period (ca. 635-542 Mya) in most cases, which is much closer to Dr. Meyer’s timetable.

    Dr. Meyer may have gotten his facts somewhat wrong on the antiquity of protein folds, but he was basically right on proteins – which is what my OP discussed. And you still haven’t refuted the arguments in Dr. Axe’s paper, The Case Against a Darwinian Origin of Protein Folds, which Meyer cites repeatedly in Darwin’s Doubt and Signature in the Cell.

  84. 84
    Mung says:

    Do IDer’s know know about ancient genes?

    These signaling pathways pre-date the animals that use them now. Based on genomic analyses, these signaling molecules have been around well before the first bilaterian animals ever existed. They are expressed in organisms that lack these body axes completely. Even more surprising, many of the molecules used to make complex structures such as muscles, eyes, and brains also predate their use for those purposes.

    http://www.evolutionnews.org/2.....01891.html

  85. 85
    Arthur Hunt says:

    vjtorley, you continue to rely on arguments made by Axe and Meyer that concern the supposed rarity of function in protein sequence space. If Axe and Meyer were correct, then the Southern corn leaf blight epidemic of 1969-1970 cannot have possibly occurred – the “math” of Axe and Meyer (and Behe) is pretty clear on this, SCLB is an impossibility if they are correct.

    Are you of the opinion that this epidemic is a fiction? If not, then why to you cling to an incorrect view of protein structure, function, and evolution, one that demands that you deny obvious historical facts such as this? Has the Agriculture Dept. of the Discovery Institute come up with a way to revise history when it comes to this series of events? I am curious as to your thought processes when it comes to this subject.

  86. 86
    Mung says:

    Nick Matzke then: It’s true VJT doesn’t really address folds.

    Nick Matzke now: Wow, that’s a really long way of avoiding admitting error in your Opening Post, VJ Torley.

    The OP doesn’t even deal with protein folds and Nick knows it.

  87. 87
    Virgil Cain says:

    Arthur Hunt- Corn is the result of artificial selection. That means variations occurred that normally would not have. This has been pointed out to you before and you ignored it then too.

    Willful ignorance is not an argument.

    T-cytoplasm was a man-made change in corn plants used to foster the quick and profitable production of high-yielding, hybrid corn seed.

    from blight in the corn belt

  88. 88
    Mung says:

    vjtorley:

    Dr. Meyer may have gotten his facts somewhat wrong on the antiquity of protein folds, but he was basically right on proteins…

    I don’t recall Meyer making any claim about the antiquity of proteins folds. I think he should at least be credited with understanding they are as old as the oldest prokaryote.

    The debate is over whether any new protein folds were needed for the Cambrian animals.

    The alternative is front-loading. 🙂

  89. 89
    Arthur Hunt says:

    Virgil Cain, the sorts of random shufflings and rearrangements that underlie the SCLB epidemic happen in nature all the time. And they yield similar phenotypic outcomes.

    You seem to be claiming that some plant breeders somewhere in the 1950s deliberately, using recombinant DNA methods, crafted the mitochondrial genome seen in CMS-T corn. That’s just preposterous. The fact is that the trait was the result of random genome shuffling that created a gated ion channel from scratch. That’s random shuffling, and Axe et al. claim that such processes cannot, regardless of the context in which the trait originated, produce something as complex as a multi subunit gated ion channel.

  90. 90
    Virgil Cain says:

    Arthur Hunt- You have no idea if the shuffling is random or by design

    You seem to be claiming that some plant breeders somewhere in the 1950s deliberately, using recombinant DNA methods, crafted the mitochondrial genome seen in CMS-T corn.

    Nope. Try again.

    The fact is that the trait was the result of random genome shuffling that created a gated ion channel from scratch.

    That is your opinion and not a fact.

    The fact is corn is the result of many generations of human tinkering, including the cytoplasm. And because of that fact alone weird things happened.

  91. 91
    Mung says:

    Art, neither Axe nor Meyer have anything against random shuffling.

    If you shuffle a poker deck you get a card belong to one of 13 ranks and one of 4 suits. You don’t get a community chest card from Monopoly.

  92. 92
    Arthur Hunt says:

    So, Virgil Cain, you continue to insist that plant breeders in the 50’s and 60’s knew, from first principles, that a gated ion channel would lead to the CMS trait. That is, after all, the only alternative to the mechanism that was (and is) actually in play. How, pray tell, did breeders manage this impressive feat of logic, given that the relevant theory (the chemisomotic hypothesis) had yet to be formulated in the 50’s and wasn’t widely accepted until the late 70’s?

    The fact is, we know enough about the enzymes that catalyze homologous and non-homologous recombination to state in no uncertain terms that, as far as the CMS-T trait is concerned, the rearrangements involved were random, not guided towards the production of this specific gated ion channel.

  93. 93
    Arthur Hunt says:

    Mung, if Axe et al. are correct, then the chances that a breeder could hit this jackpot via random shuffling are so low as to completely preclude the generation of the trait. History says otherwise.

    Axe et al. may have nothing against shuffling as a biochemical occurrence, but they most definitely rule out this process as a way to new protein-coding genes. History tells us that they are wrong.

  94. 94
    Virgil Cain says:

    Arthur Hunt:

    So, Virgil Cain, you continue to insist that plant breeders in the 50’s and 60’s knew, from first principles, that a gated ion channel would lead to the CMS trait.

    Nonsense. The fact is that trait would never have appeared if we had never messed with corn.

    That is, after all, the only alternative to the mechanism that was (and is) actually in play.

    More nonsense.

    You think it was all sheer dumb luck. How, exactly, is that science?

    The fact is, we know enough about the enzymes that catalyze homologous and non-homologous recombination to state in no uncertain terms that, as far as the CMS-T trait is concerned, the rearrangements involved were random, not guided towards the production of this specific gated ion channel.

    The fact is we have no idea if recombination is random or part of the design of organisms. And the fact is all you have to explain it is sheer dumb luck and the fact is positions that rely on sheer dumb luck are not scientific.

    As far as anyone knows this new gene was a result of human intervention and the reaction the organism had towards that.

  95. 95
    Arthur Hunt says:

    The fact is that trait would never have appeared if we had never messed with corn.

    Since CMS is known to occur in plants in nature, quite apart from any sort of breeding, this statement implies that, according to Virgil Cain, there was no recombination in the mitochondria of the wild relatives of maize. And that this capacity was restored by ancient Americans some thousands of years ago.

    Of course we know this is not correct.

  96. 96
    Arthur Hunt says:

    I would note that, by equating “random” with “non-scientific”, Virgil Cain is essentially tossing out many (most, all?) uses of formal statistical testing as tools in science (and engineering, for that matter).

  97. 97
    Mung says:

    Art, there’s nothing new about gated ion channels.

  98. 98
    Arthur Hunt says:

    Mung, do you mean this in a book-learning sense (we’ve known about gated ion channels for a long time) or an evolutionary sense (gated ion channels are ancient proteins)?

  99. 99
    Mung says:

    Arthur Hunt:

    Mung, do you mean this in a book-learning sense (we’ve known about gated ion channels for a long time) or an evolutionary sense (gated ion channels are ancient proteins)?

    Both. They are essential for life as we know it.

  100. 100
    Virgil Cain says:

    And more pap from Arthur Hunt:

    Since CMS is known to occur in plants in nature, quite apart from any sort of breeding, this statement implies that, according to Virgil Cain, there was no recombination in the mitochondria of the wild relatives of maize.

    Wrong again, Art. Recombination is a design feature of living organisms. Meaning organisms were designed to do so.

    I would note that, by equating “random” with “non-scientific”,

    Except I didn’t do that. What are you, 5 years old?

    Even Dawkins said that science can only allow so much luck. Saying that generations of recombinations- ie random shuffling- produces new genes, is saying nothing more than sheer dumb luck produced the genes.

    What I said was:

    The fact is we have no idea if recombination is random or part of the design of organisms. And the fact is all you have to explain it is sheer dumb luck and the fact is positions that rely on sheer dumb luck are not scientific.

    As far as anyone knows this new gene was a result of human intervention and the reaction the organism had towards that.

    The organism engineered the new gene, Art.

  101. 101
    NickMatzke_UD says:

    83
    vjtorleyDecember 28, 2015 at 8:38 am
    Hi Nick Matzke,

    You write:

    I’ve known about Grishin’s work for a long time. Whether or not I ever had occasion to reference it is a different question – I don’t think I’ve ever written an extended discussion of the origin of protein folds. But, as it happens, I used to save potentially useful references on CiteUlike, and lo and behold: http://www.citeulike.org/user/matzke/tag/evolution . That’s 2 Grishin articles and several others on the same topic. In April 2005.

    You did indeed save two articles by Grishin in 2005 (under the name “matzke” rather than “Nick Matzke,” which is why my Google search never picked it up), but you didn’t use them for a long time afterwards. I might add that the articles by Grishin which you saved were written in 2001 and 2002 – i.e. at least two years before the publication of Dr. Douglas Axe’s paper, “Estimating the prevalence of protein sequences adopting functional enzyme folds” (Journal of Molecular Biology, 2004 Aug; 341(5):1295-315). Neither of the papers you saved even attempts to estimate the antiquity of the various protein folds found in animals – in fact, neither paper even mentions animals as such (Metazoa). So the relevance of these articles to Intelligent Design or to Dr. Meyer’s book, Darwin’s Doubt, is highly debatable.

    Aggggh. There are two claims Meyer makes:

    1. The natural evolution of new protein folds is wildly improbable.

    2. The Cambrian Explosion required lots of new protein folds.

    Grishin’s work (and related work) addresses #1. He shows examples where minor mutational changes cause proteins to shift fold — even while maintaining function!

    Point #2 is addressed by looking at the distribution of folds amongst organisms, and observing that there are few folds unique to bilaterian animals. This has been obvious for years — Ohno’s paper on the pan-animalian genome points out that these bilaterians all share their basic gene/protein set, and if this is true, then anyone who knows that folds are even more conserved than proteins on average knows that the folds must be mostly shared also.

    But point #2 is also addressed, more explicitly, also in this very thread, in this article:

    Song Yang, Philip E. Bourne (2009). The Evolutionary History of Protein Domains Viewed by Species Phylogeny. PLoS ONE 4(12): e8378. doi:10.1371/
    journal.pone.0008378 http://www.plosone.org/article.....tation=PDF

    How can you have possibly missed this?? It’s like you have short-term memory loss or something…

    From what I can tell (h/t Bob O’H), you never mentioned Grishin’s work in your posts until June 2014 – and that was in a very brief Twitter post.

    Who cares? I even mentioned in my Panda’s Thumb review of Meyer that I was doing it quickly and wouldn’t have time to introduce everything in a for-beginners way, or put in all relevant citations.

    I think you are just grasping at straws, trying to find any possible way of saving Meyer’s reputation, and by implication yours.

    Note that in real science, it is better to just fess up to mistakes, issue a correction, and move on. That’s how you build a reputation in science.

    You also write:

    Meyer asserted the Cambrian explosion required many new protein folds. This is clearly false and has been disproven, and Meyer definitely should have known this, and his defenders should have also (Most of the folds are indeed shared with fungi — but also closer outgroups — choanoflagellates, sponges, etc.) Until you admit Meyer made a mistake there, there is little point in continuing.

    I really think you’re being a bit rude to Dr. Meyer here. Take a look at his Acknowledgments page (p. 414), where he states: “I’d also like to acknowledge the two anonymous biologists and two paleontologists who gave such careful attention to improving the scientific rigor and accuracy of the manuscript during the peer-review process.” If there are any scientific mistakes in Meyer’s book, it’s these guys who should take the fall for it, not Meyer.

    What? The author isn’t responsible for what he writes? This is, though, evidence that whatever reviewers Meyer got were not serious people. Probably they were either creationists or off-the-deep-end people like Mark McMenamin.

    He did, after all, do his level best to ensure that his book from free from mistakes. He is, as he states, “not a biologist, but a philosopher of biology.”

    There were so many mistakes in the book, I doubt this is true. He did his level best to make a pro-ID case from the Cambrian Explosion, based on what he thought he learned about the topic in the 1980s, and doing his best to ignore everything that has happened since then indicating that the “lawn of phyla” view, popular in the 1980s, is incorrect. Then he stuck in a bunch of basically irrelevant material, like assertions about how lots of protein folds had to originate in the Cambrian, basically because he thought it helped his argument to cite Axe.

    You write that most of the protein folds found in animals are indeed shared with fungi. Since you’re a biologist working in the field, I’ll take your word for it, although I still have a question as to how scientists determine that fold A and fold B are in fact the same fold: is “sameness” a clear-cut term, in this context, or does “the same” just mean highly similar?

    It is a safe generalization that if two protein sequences have statistical similarity indicating homology, then they have the same structure. Note that this generalization is not absolute — Nick Grishin and colleagues have collected cases where similar sequences produce different structures. But this is rare.

    This is protein homology 101, if you don’t understand stuff like this, what basis do you have for even having an opinion on these topics, or on the correctness of Meyer?

    Granting that the protein folds found in animals are more ancient than animals themselves, it would appear that the protein folds shared by animals and fungi go back about 1,300 million years, since that’s the time when timetree.org estimates that animals and fungi diverged. (Animals and plants diverged about 200 million years earlier, but you do not claim that plants possess these protein folds too.) However, the actual proteins that are used by the various phyla of animals are likely to be far more recent, and may well go back no further than the Ediacaran period (ca. 635-542 Mya) in most cases, which is much closer to Dr. Meyer’s timetable.

    100 million years wrong would still quite a lot of wrong, actually. And once it’s conceded that the protein folds came long before the Cambrian Explosion, then you’ve conceded that Meyer was wrong to raise Douglas Axe in the context of the Cambrian Explosion! Game over!

    Dr. Meyer may have gotten his facts somewhat wrong on the antiquity of protein folds, but he was basically right on proteins – which is what my OP discussed.

    Heh! You’ve argued in a circle! The whole friggin’ point of Ohno’s article on the pan-animalian genome was that the gene and protein complements are basically shared across bilaterians as well! There was, in fact, not a huge amount of origination of genes and proteins required to produce the Cambrian phyla, and we know this because they all have the same basic complement of genes and proteins. The differences that they have are basically due to differential duplication of genes and subsequent modification of genes, and sometimes rearrangement/recombination of pre-existing gene chunks. All of this is totally obvious from actually reading Ohno with any care — but you and Meyer just can’t seem to get it through your skulls, I think because have such a strong, unquestioned prior belief that the origin of morphological diversity just has to involve lots of new genes and new proteins. Ohno’s point was that the main thing going on was just redeployment (different regulation) of preexisting genomes.

    This was Rasmussen’s original point also! It’s just stunning that you are still trying to resuscitate Meyer’s dead horse on this point.

  102. 102
    Barry Arrington says:

    Nick:

    Note that in real science, it is better to just fess up to mistakes, issue a correction, and move on.

    Then why haven’t you fessed up to your mistake that I pointed out in comment 5, issued a correction, and moved on?

    BTW, when you are going to answer the question that has been on the table for two and a half years? (See here) It is a simple question Nick.

  103. 103
    Andre says:

    Nick

    Since when is computer simulations facts? Your litrature bluff are not real world examples, they are intellegent designed software that are working towards a goal to achieve a specific result. This to you are facts? Then it stands to reason that you are a very religious person taking assumptions by faith and converting them with your weak intentional states to facts. Shameful. You are what we call a religious zealot.

  104. 104
    vjtorley says:

    Hi Nick,

    I’d like to address a brief remark of yours in #101 above:

    The whole friggin’ point of Ohno’s article on the pan-animalian genome was that the gene and protein complements are basically shared across bilaterians as well! There was, in fact, not a huge amount of origination of genes and proteins required to produce the Cambrian phyla, and we know this because they all have the same basic complement of genes and proteins. The differences that they have are basically due to differential duplication of genes and subsequent modification of genes, and sometimes rearrangement/recombination of pre-existing gene chunks. All of this is totally obvious from actually reading Ohno with any care — but you and Meyer just can’t seem to get it through your skulls, I think because have such a strong, unquestioned prior belief that the origin of morphological diversity just has to involve lots of new genes and new proteins. Ohno’s point was that the main thing going on was just redeployment (different regulation) of preexisting genomes.

    Might I remind you that Ohno’s hypothesis of a pan-animalian genome is just that: a hypothesis.

    Might I also remind you that even if all animal phyla turn out to have the same basic complement of genes and proteins, there is also abundant evidence of genes and proteins which are unique to each phylum. The origin of these genes and proteins needs to be accounted for.

    As I have repeatedly stated in my comments above, the question of when these genes and proteins originated does not concern me greatly. Meyer maintains in his book, Darwin’s Doubt (p. 189), that many of them must have originated in (or very shortly before) the Cambrian. On this point, he is probably wrong, as you’ve pointed out. However, in his 2001 article, Biology’s Big Bang, which I cited above, Meyer briefly considers the possibility that Ohno’s “pan-animalian genome” theory may be correct after all, but points out that even if it were true, it would raise a problem for Darwinism: “Specific genes would have arisen well before they were used, needed or functionally advantageous.”

    But even if Meyer were wrong here as well, and the genes in the ancestral pan-animalian genome turned out to have functions that were later co-opted or ex-apted by their Cambrian descendants, the much larger point which Meyer makes on pages 192 to 207 of his book, in which he discusses the work of Dr. Douglas Axe, is that the likelihood of even one functional protein fold originating on the primordial Earth is vanishingly low – especially when we’re talking about the kinds of long-chain proteins required for the appearance of animal life. This is the argument on which Meyer’s whole case stands or falls.

    In your reviews of Darwin’s Doubt, you’ve failed to address this central argument, instead focusing your fire on peripheral issues like the duration of the Cambrian explosion (frankly, who cares if it was 10 million years or 30 million?) and whether Anomalocaris was an arthropod or not.

    You ask why I haven’t discussed the article by Yang and Bourne. My take on the article is that while its phylogeny is plausible enough, it fails to establish that the mechanisms which it mentions could have actually generated new protein domains, as proposed by the authors. In particular, the authors nowhere reference Dr. Axe’s work or his arguments.

    You also mention Grishin’s work, which, you say, “shows examples where minor mutational changes cause proteins to shift fold — even while maintaining function!”

    For a rebuttal of Grishin’s claims, I suggest you have a look at this article by Casey Luskin. Luskin argues that Grishin “assumes from the outset that there are Darwinian pathways, but it does not demonstrate that those pathways exist… Rather than showing how natural selection and random mutation might have increased the information in these genes, what the paper primarily finds is mere sequence homology… No step-by-step Darwinian pathway for the evolution of … proteins is given.” The article quotes Professor Michael Behe, who writes: “Like the sequence analysts, I believe the evidence strongly supports common descent. But the root question remains unanswered: What has caused complex systems to form?”

    If you think that Luskin has done Meyer a grave injustice and that Meyer’s central argument is badly flawed, then by all means, make your case. But before you do, please read Dr. Axe’s article, Correcting Four Misconceptions about my 2004 Article in JMB, in which he responds to common criticisms of his work by Venema, Matheson, Hunt and others.

    And finally, if you think Dr. Axe’s claims are wrong, then I suggest you devote a full-length post on Panda’s Thumb to that very issue. I think it’s fair to say that if you could successfully refute the arguments in Axe’s 2010 paper, The Case Against a Darwinian Origin of Protein Folds, then the scientific case for biological (as opposed to cosmological) Intelligent Design would come crashing to the ground.

    So get to work, Nick. What’s holding you back?

  105. 105
    Mung says:

    Nick Matzke:

    Ohno’s paper on the pan-animalian genome points out that these bilaterians all share their basic gene/protein set…

    This is simply false, Nick. Ohno’s paper shows no such thing. (Yes, I’ve read the paper.)

    …and if this is true, then anyone who knows that folds are even more conserved than proteins on average knows that the folds must be mostly shared also.

    I also think it’s reasonable to assume that you know it is false considering your further qualification “if this is true.”

    Have you even read the paper Nick?

  106. 106
    Mung says:

    Nick Matzke:

    This is protein homology 101, if you don’t understand stuff like this, what basis do you have for even having an opinion on these topics, or on the correctness of Meyer?

    That’s an easy one, Nick. We look at other things Meyer said in the same argument, the things you keep wanting to ignore, the things we know are true.

    New genes
    New proteins
    New cell types
    New organs

    These things are simpler to validate and their origins in the Cambrian animals is far less controversial.

    Which of those did Meyer get wrong, Nick?

    From the above, Meyer makes an inference about new protein folds. It’s an inference. The problem you have, and other critics like Rumraket, is that you fail to properly grasp the argument and instead of addressing the argument you try to focus on details that are of little to no relevance.

  107. 107
    Mung says:

    Nick Matzke:

    The differences that they have are basically due to differential duplication of genes and subsequent modification of genes, and sometimes rearrangement/recombination of pre-existing gene chunks.

    So, new genes and new proteins, and by your own references to Grishin this could easily result in new folds. That’s what you’re saying? Help me out here Nick.

  108. 108
    Mung says:

    The vertebrate homeotic complex comprises four distinct Hox gene clusters (Hox A, B, C, D) that are organized into thirteen homology (or paralogue) groups.

    http://people.ucalgary.ca/~bro.....o/hox.html

  109. 109
    Mung says:

    I have a couple questions for people to consider.

    If it’s such a simple thing to evolve new protein folds, why are there not more of them?

    If it’s such a simple thing to evolve new protein folds, why not believe that new ones arose during the Cambrian explosion?

  110. 110
    Zachriel says:

    Mung: If it’s such a simple thing to evolve new protein folds, why are there not more of them?

    Is the choice of extant folds contingent or necessary? A frozen accident, or optimized through selection? To what degree? The geometry of the vast Protein Universe is still largely unknown.

    Mung: If it’s such a simple thing to evolve new protein folds, why not believe that new ones arose during the Cambrian explosion?

    Some did, but they are small in number. Most folds were inherited. Think of it as an erector set. Once you have the basic components, you can build most anything you want. In the case of proteins, the components can even be extensively modified.

  111. 111
    Virgil Cain says:

    Only artificial selection can optimize. Natural selection is a process of elimination. It is not an optimizing process.

  112. 112
    Axel says:

    @florabama #22

    ‘Nick Matzke — biology’s Baghdad Bob.’

    How about :

    Nick Matzke – biology’s Donald Rumsfeld :

    “That’s not the way the world really works anymore.” He continued “We’re an empire now, and when we act, we create our own reality. And while you’re studying that reality—judiciously, as you will — we’ll act again, creating other new realities, which you can study too, and that’s how things will sort out. We’re history’s actors … and you, all of you, will be left to just study what we do.”

    Unfortunately, in means modern man is doomed thereby to hear the endlessly repeated refrain : “Gee! Isn’t Evolution wonderful. It never ceases to surprise us ? And there were we thinking bla bla bla.”

  113. 113
    PaV says:

    Nick Matzke:

    I’m just coming onto the scene, but a few reactions nonetheless:

    NM says:

    VJ Torley, your post is silly in several ways:

    1. “New genes” and “new proteins” are not the same thing as “new protein folds”. You can have many different kinds of proteins that all draw from the same folds. You can’t quote sources talking about new genes/new proteins/new information and just blithely assume this automatically means new folds. Rasmussen gets this, Meyer misses this, you miss this.

    Nick, this is pure silliness. The ‘critical’ need of specificity has to do with “new proteins,” not “new folds.” I think it’s fairly obvious that the combinatorial space for DNA is much, much more specified, and hence, improbable, than the ‘physical space’ that proteins require as they fold.

    Can you not see that there are infinitely less configurations of ‘folds’ as compared to configurations of ‘new proteins’? Then why this silly attempt to ‘impeach’ the scientific credentials of Meyer?

    2. The pan-animalian genome idea means that all of these animals are built with not only the same basic folds, but the same basic gene set. This is dramatically less of an “information explosion” than would be required if they all needed different genes.

    And where is the ‘evidence’ for this “pan-animalian genome”? It’s no more than a theoretical construct built out of necessity.

    (All that said, Ohno isn’t even particularly an expert on the Cambrian Explosion. The pan-animalian genome idea is a good one nevertheless. But he misses things, which the ID advocates then naively take as gospel truth, since they have such a blind and un-nuanced idea of “authority” in science.

    E.g., because he’s not a paleontologist, one thing Ohno misses, IIRC, is that there is clear evidence of bilaterians in the Precambrian — trackways and burrows indicating billaterial symmetry, a coelom, etc., and these continually increase in complexity through the small shelly fossils, only reaching the “classic” Cambrian Explosion tens of millions of years later. This is all true regardless of one’s interpretation of the Edicarans etc. Thus, it’s idiotic to say, as Meyer does, that Ohno’s hypothesis means “the pananimalian genome ar[ose] well before its expression in individual animals.” Fossil traces of bilaterians are there before the Explosion, they had worm-level complexity, all of those common genes between all the phyla basically are what is required to specify a bilaterian body plan, which is what worms have.

    But, Nick, you’ve succeeded here in missing Meyer’s devastating critcism of Ohno’s hypothesis: viz., as pointed out in bold type by vjt:

    While Ohno’s hypothesis does preserve the core evolutionary commitment to common descent (or monophyly), it nevertheless has a curious feature from the standpoint of neo-Darwinism. In particular, it envisions the pananimalian genome arising well before its expression in individual animals.115 Specific genes would have arisen well before they were used, needed or functionally advantageous. Hence, the individual genes within the pananimalian genome would have arisen in a way that, again, would have made them imperceptible to natural selection. This not only creates a problem for the neo-Darwinian mechanism, but it also seems to suggest, as Simon Conway Morris has recently intimated,116 the need for foresight or teleology to explain the Cambrian explosion. [My italics]

    Again, Nick, you miss Meyer’s point. The whole notion of a “pan-animalian” genome is hypothetical, and, worse, contradictory to Darwinian expectations.

    3. Bringing in the origin of eukaryotes is also silly, since eukaryotes arose probably a billion years before the Cambrian. Whether or not new protein folds originated with eukaryotes (probably, although many many folds are shared between eukaryotes and prokaryotes), this is in no possible way an argument that new folds originated in the Cambrian. This is totally obvious! How can you not get this is, in a post allegedly taking on Rasmussen head-on?

    Nick, this is blather. Where did you pull up the “billion years” from? Is it your ‘guess’? And, again, who cares about protein folds when we’re talking about new proteins. Where does the information for these new proteins come from? (And, this says nothing of the new “co-chaperone” proteins that would be necessary for folding)

    Even the intended argument is hazy, but seems to be something like: the origin of the first eukaryotic cell, a “simple” transition, required lots of new proteins and protein folds, therefore the origin of new cell types must also. But that’s just crazy. Different cell types in a multicellular eukaryote will have much more in common than a eukaryote cell and a prokaryote cell. The origin of eukaryotes is probably the biggest and most fundamental evolutionary event apart from the origin of life itself. The origin of multicellularity, the Cambrian Explosion (not the same thing as the origin of multicellularity, another thing ID/creationists often miss), etc. are all minor by comparison.

    Nick, you’ve moved from blather to bluster here.

    What was the ‘first’ eukaryotic cell? Was it yeast? Now compare a yeast cell to an axion. Is this “minor by comparison”? All of this is speculation, yet you act as if all of this is perfectly known.

    These kinds of catastrophic, fundamental mistakes and lack of knowledge of absolute basics — which are totally obvious to anyone who has a basic grasp of the field — are exactly why biologists are so dismissive of Meyer, ID, and UD. Imagine if someone went around claiming that the U.S. Constitution was fatally flawed, and then claimed that the First Amendment was about gun control. Most people would just shake their heads and walk away, concluding that kooks who can’t get these basics right aren’t worth listening to.

    Wow. Here’s what you said just above: “The origin of eukaryotes is probably the biggest and most fundamental evolutionary event apart from the origin of life itself.” Did you notice you used the word “probably”? I did.

    You want to compare contentious, poorly known areas of knowledge to clearly known areas of knowledge? We KNOW what the U.S. Constitution says. We know what the First Amendment says. But we don’t know if: (i) eukaryotes developed a “billion years ago,” or (ii) what the “evolutionary” transition between prokaryotes and eukaryotes looked like.

    Bluster is still not a substitute for rational argument.

  114. 114
    Mung says:

    The group believed to be closest to the animals is the Choanoflagellates. Single-cell with asexual reproduction.

    So on the road to all the Cambrian animals we need multi-cellularity and sexual reproduction, at a minimum.

  115. 115
    Mung says:

    More evidence for the mystical front-loading hypothesis:

    https://en.wikipedia.org/wiki/Meiosis

    https://en.wikipedia.org/wiki/Sexual_reproduction

    There simply must have been a single-cell, asexually reproducing, front-loaded organism.

  116. 116
    Arthur Hunt says:

    vjtorley,

    I see that you mentioned Axe’s alleged response to my discussion of Axe’s 2004 article. What you fail to point out that Axe almost completely ignored my criticisms and conclusions, and he continues, to this day, to pretend that these valid arguments do not exist.

    To briefly summarize: in the purported response you linked to, Axe said (among other things – the other alleged responses to my essay miss the points entirely):

    According to Hunt, I “molded a variant that would be exquisitely sensitive to mutation.” [2] Venema expressed the same concern, that the starting sequence I used was “intentionally ‘hamstrung’ with multiple mutations to render it far less functional than its natural counterpart.” [7]
    Both Hunt and Venema seem to think the outcome would have been more favorable (i.e., functional sequences would have been more prevalent) had I used the highly proficient natural enzyme as a starting point rather than the handicapped version. Actually, as a demonstration will show, the opposite is true.

    Axe’s demonstration does no such thing. Furthermore, he completely ignores the crux of my criticism. Referring to Figures 1 and 3 from my essay: The point of Axe’s study was to enumerate the totality of sequences that could give rise to a particular functionality. This totality of sequences is represented by the base of the hill shown in Fig. 1. To do this, Axe crafted, by extensive mutagenesis and deliberate selection, a feeble enzyme that would be exceedingly sensitive to mutation. Importantly, the variant he created was temperature-sensitive. This means that he deliberately molded an enzyme that would have very steep sides (that is the necessary outcome of a ts mutant – even tiny straying from the ts sequence necessarily will destroy function) and a very small base, as I show in Fig. 3. What Axe claims is that the base of the hill in Fig. 3 is, not just representative to that of the natural enzyme shown in Fig. 1, but identical to the base of the hill shown in Fig. 1. He not only provides zero evidence, or even theoretical argument, for this claim, he ignores the fact that the hill that defines the ts variant will undoubtedly have a very different shape, including at its base. In other words, he completely ignores the fundamental flaw in his study, and he continues to this day to pretend that the flaw does not exist.

    At the end of my discussion of Axe’s 2004 article my essay, I state:
    10^-10 -> 10^-63 (or thereabout): this is the range of estimates of the density of functional sequences in sequence space that can be found in the scientific literature. The caveats given in Section 2 notwithstanding, Axe’s work does not extend or narrow the range.

    This statement was true in 2004, it was true in 2007, and it is true today. As long as this is the case, any arguments that rely on Axe’s work to “prove” the unevolvability of proteins are wrong.

  117. 117
    Mung says:

    Proteins are easy to evolve, except in the Cambrian. there’s no evidence of any evolution at all during the Cambrian. Just a bunch of shuffling.

    It’s like coming up with a whole bunch of new card games just by shuffling a deck of cards.

  118. 118
    Zachriel says:

    Mung: The group believed to be closest to the animals is the Choanoflagellates. Single-cell with asexual reproduction.

    Levin & King, Evidence for sex and recombination in the choanoflagellate Salpingoeca rosetta, Current Biology 2013.

    Birds do it, bees do it
    Even educated fleas do it
    Let’s do it, let’s fall in love.

    Romantic sponges, they say, do it
    Choanoflagellates do it
    Let’s do it, let’s fall in love.

    Mung: Proteins are easy to evolve, except in the Cambrian. there’s no evidence of any evolution at all during the Cambrian.

    There’s plenty of protein evolution associated with the advent of metazoa, but the question concerned protein folds.

  119. 119
    Virgil Cain says:

    If you want to talk about protein folds you need to be prepared to talk about chaperones. And once you start talking about chaperones evolutionism falls silent.

  120. 120
    jerry says:

    If new proteins arise by reshuffling then evidence will be in the genomes of current species. Has any been provided?

    Reshuffling of what part of the genomes is supposedly the source of new proteins? Current coding regions? Non-coding regions?

  121. 121
    NickMatzke_UD says:

    119
    Virgil CainDecember 29, 2015 at 5:14 pm
    If you want to talk about protein folds you need to be prepared to talk about chaperones. And once you start talking about chaperones evolutionism falls silent.

    Where do you guys come up with this stuff?

    Here, let me help:

    https://scholar.google.com/scholar?q=Evolution+chaperones&btnG=&hl=en&as_sdt=0%2C38

  122. 122
    NickMatzke_UD says:

    120
    jerryDecember 29, 2015 at 5:16 pm
    If new proteins arise by reshuffling then evidence will be in the genomes of current species. Has any been provided?

    Reshuffling of what part of the genomes is supposedly the source of new proteins? Current coding regions? Non-coding regions?

    https://scholar.google.com/scholar?q=domain+shuffling&btnG=&hl=en&as_sdt=0%2C38

  123. 123
    Mung says:

    Nick Matzke: Where do you guys come up with this stuff?

    I keep a barrel of it out on the patio.

    Do you have an explanation why the shuffling stopped in the Cambrian? The dealer got tired?

  124. 124
    Mung says:

    Zachriel:

    There’s plenty of protein evolution associated with the advent of metazoa, but the question concerned protein folds.

    We could go by what you say, but we’re talking about what Meyer wrote, so I am going to go with what Meyer says on this one. For example:

    “The Cambrian animals exhibit structures that would have required many new types of cells, each requiring many novel proteins to perform their specialized functions. But new cell types require not just one or two new proteins, but coordinated systems of proteins to perform their distinctive cellular functions.”


    New types of cells.
    Novel proteins.
    Coordinated systems of proteins.

    Now if we agree there were new proteins, and new protein folds are do darned easy to evolve, what made them stop during the Cambrian?

    Was there like this protein fold traffic cop out there telling evolution to stop, that all the protein folds had already been discovered, and that there was no need for any more?

    Sure, that must be it.

  125. 125
    Virgil Cain says:

    Yes, Nick, we already know that you are a grand equivocator and a literature bluffer. Please tell us which of those papers demonstrates that blind and undirected chemical processes- ie natural selection, drift and neutral changes can produce chaperones. The first paper fails in that regard…

  126. 126
    jerry says:

    https://scholar.google.com/scholar?q=domain+shuffling&btnG=&hl=en&as_sdt=0%2C38

    What percentage of new genes originate this way? Are they shufflings of another coding region? A non-coding region?

    I assume that if there is a reshuffling, there is knowledge of what got reshuffled?

    What percentage of genes can they not identify their origin? Why can they not identify an origin?

    The answers to these questions would go a long way to answering questions people have about the origin of coding areas.

    I would assume the answers to these questions would be of interest to researchers and part of research reviews.

  127. 127
    Mung says:

    Nick Matzke: All of this is totally obvious from actually reading Ohno with any care — b

    Haha. Good one Nick.

    Reasons for Invoking the Presence of the Cambrian Pananimalia Genome. Assuming the spontaneous mutation rate to be generous 10^-9 per base pair per year and also assuming no negative interference by natural selection, it still takes 10 million years to undergo 1% change in DNA base sequences. It follows that 6-10 million years in the evolutionary time scale is but a blink of an eye. The Cambrian explosion denoting the almost simultaneous emergence of nearly all the extant phyla of the kingdom Animalia within the time span of 6-10 million years can’t possibly be explained by mutational divergence of individual gene functions. Rather, it is more likely that all the animals involved in the Cambrian explosion were endowed with nearly the identical genome, with enormous morphological diversities displayed by multitudes of animal phyla being due to differential usages of the identical set of genes. This is the very reason for my proposal of the Cambrian pananimalia genome.

    That the stated reason, by the author.

    Ohno’s paper on the pan-animalian genome points out that these bilaterians all share their basic gene/protein set…

    An actual reading, with care, shows that it does no such thing.

  128. 128
    Arthur Hunt says:

    Mung, the two sentences immediately following the one you bolded say exactly what Nick is saying.

    Methinks you’ve been trying again to slake your thirst by eating sugar. Gotta stop doing that. Go ahead, drink some water.

  129. 129
    vjtorley says:

    Hi Arthur Hunt,

    Thank you for your post. Regardless of whether they are justified or not, the methodological criticisms you make of Dr. Axe’s research are certainly substantive, and I think they deserve a fair hearing. Dr. Ann Gauger has contacted me previously and informed me that BioComplexity is happy to publish scientific critiques of Intelligent Design, in addition to scientific articles supporting the case for ID. If you wish to compose a short article outlining your concerns with Dr. Axe’s protein studies, then I would be delighted to forward it to Dr. Axe and Dr. Gauger. I’m sure they’d publish it: after all, they could hardly ignore it.

    I do, however, wish to take issue with a statement toward the end of your post, which you made back in 2004, and which you still endorse today:

    10^-10 -> 10^-63 (or thereabout): this is the range of estimates of the density of functional sequences in sequence space that can be found in the scientific literature. The caveats given in Section 2 notwithstanding, Axe’s work does not extend or narrow the range.

    First, if this statement were true, it would stand as a living reproach to biologists all around the world. 10^-10 to 10^-63 is an uncertainty spanning 53 orders of magnitude – and you’re telling me that after 11 years of research, biologists still haven’t succeeded in narrowing that estimate?!?! That’s disgraceful. Someone needs to get off their lazy backsides.

    Second, what kind of proteins are we talking about here? In particular, how many amino acids? As biophysicist Dr. Cornelius Hunter has previously pointed out (see my post, The dirty dozen: Twelve fallacies evolutionists make when arguing about the origin of life), the larger proteins (150+ amino acids) appear to be needed for all known forms of life, and there are still no obvious gradual pathways to forming these proteins.

    Dr. Hunter adds:

    And finally there are several studies on slightly more complex, challenging proteins, all of which come in at around 10^60 – 10^80 attempts required.

    10^60 – 10^80 is very different from your estimate of 10^10 to 10^63. May I ask: what’s going on here?

  130. 130
    Mung says:

    Arthur Hunt:

    Mung, the two sentences immediately following the one you bolded say exactly what Nick is saying.

    These two sentences?

    Rather, it is more likely that all the animals involved in the Cambrian explosion were endowed with nearly the identical genome, with enormous morphological diversities displayed by multitudes of animal phyla being due to differential usages of the identical set of genes.

    This is an inference. The paper does not show or point out what Nick claims it does. It merely declares it must be so. The alternative is simply too unbelievable.

  131. 131
    Mung says:

    Art, what does the Ohno paper say about protein folds?

  132. 132
    gpuccio says:

    vjtorley:

    I suspect that the 10^10 figure is derived from the Szostak paper. I have discussed many times here in detail, even recently, why that paper is completely irrelevant to the discussion.

  133. 133
    Mung says:

    More Meyer:

    Third, building new animal forms requires generating far more than just one protein of modest length. New Cambrian animals would have required proteins much longer than 150 amino acids to perform necessary, specialized functions.

    Who here is denying that the Cambrian animals would have required proteins much longer than 150 amino acids to perform necessary, specialized functions?

    Nick?

  134. 134
    Arthur Hunt says:

    gpuccio, you are mistaken. Rather than toss around some misguided guesses, why don’t you spend some time and go through my essay in detail?

  135. 135
    Mung says:

    Levin & King, Evidence for sex and recombination in the choanoflagellate Salpingoeca rosetta, Current Biology 2013.

    This was interesting.

    Nearly all animals reproduce sexually through the production and fusion of sperm and egg cells, yet little is known about the ancestry of animal sexual reproduction. Moreover, the sexual cycle of the closest living relatives of animals, the choanoflagellates, remains completely unknown.

    Looks like steps are finally being taken to remedy that. I wonder what they will find when they study other choanoflagellates.

  136. 136
    Zachriel says:

    Mung: but we’re talking about what Meyer wrote

    Meyer: “Axe knew that as new life-forms arose during the history of life—in events such as the Cambrian explosion—many new proteins must also have arisen. New animals typically have new organs and cell types, and new cell types often call for new proteins to service them. In some cases new proteins, while functionally new, would perform their different functions with essentially the same fold or tertiary structure as earlier proteins. But more often, proteins capable of performing new functions require new folds to perform these functions. That means that explosions of new life-forms must have involved bursts of new protein folds as well.”

    This is contradicted by the relative rate of production of new proteins vs. protein folds in metazoan evolution.

    Mung: Now if we agree there were new proteins, and new protein folds are do darned easy to evolve, what made them stop during the Cambrian?

    Some new folds were introduced, but the inherited folds were generally sufficient to the task. Most of metazoan evolution was due to new uses for existing structures.

  137. 137
    Andre says:

    Zachriel

    You are talking twaddle because the fold determine the function.

  138. 138
    Zachriel says:

    gpuccio: I have discussed many times here in detail, even recently, why that paper is completely irrelevant to the discussion.

    None of your arguments were convincing, though. Szostak shows that at least some folds are fairly common in sequence space — and that’s using random sequences, which are probably much less likely to yield usable proteins than recombinations of functional proteins.

  139. 139
    Arthur Hunt says:

    Piggy backing on Zachriel’s comment, when it comes to the matter of the frequency of occurrence of function in sequence space, mRNA display is not only entirely appropriate, it is superior to some of the other things I allude to in my essay.

  140. 140
    Andre says:

    Arthur

    Are you.another RNA world preacher? Seriously? Why is it that people with dubious IQ always hang onto nonsense? Is it the superstitious side that makes you hang onto utter nonsense?

  141. 141
    Arthur Hunt says:

    Andre, what does the RNA World have to do with anything that has been mentioned in this discussion?

  142. 142
    Dr JDD says:

    Arthur, would you care to elaborate on frequency of function in mRNA space? Would you (presumably) argue that it is low?

    On another note, the whole protein fold is a bit if a misnomer IMO based on the fact with a limited ser of amino acids with grouped sidechain properties, you will inevitably get a dominant ser of protein folds. Yet protein fold combine in many different ways with each other to firm vastly different functions. Even those that perform similar functions and bind similar targets in theory will not bind the same. The immune system is a good example of that, and the limits of hypermutation to merely have an interaction with an antigen. Quite a clever design really.

  143. 143
    Mung says:

    Zachriel:

    Some new folds were introduced, but the inherited folds were generally sufficient to the task. Most of metazoan evolution was due to new uses for existing structures.

    Over at TSZ the claim is that Meyer is a liar and a con man and that he is pulling things “out of his ass.”.

    So let’s review.

    Meyer is right about new cell types.
    Meyer is right about new organs.
    Meyer is right about new genes.
    Meyer is right about new proteins.
    Meyer is right about new folds.

    Are we now going to argue over how many new folds?

  144. 144
    Mung says:

    Andre: You are talking twaddle because the fold determine the function.

    There appear to be far more proteins than protein folds, which would indicate that while folds may be necessary for function they are not sufficient for function.

  145. 145
    Virgil Cain says:

    Some new folds were introduced, but the inherited folds were generally sufficient to the task.

    Unfortunately you don’t have any idea what was and wasn’t introduced.

    Most of metazoan evolution was due to new uses for existing structures.

    Unfortunately your opinion isn’t evidence.

    The sad part is they say Meyer is wrong and yet they don’t have any idea what was required to produce the Cambrian diversity.

  146. 146
    PaV says:

    Arthur Hunt:

    I’d like to respond to your 2007 Panda’s Thumb post:

    You first give a summary of the experiment: [My few comments are interspersed]

    First, a brief overview of the experiment and results. The object of interest was the so-called large domain of the TEM-1 penicillinase, an enzyme that breaks down antibiotics related to penicillin. . . . Axe was interested in using a mutational approach to explore the constraints for forming a functional large TEM-1 domain, and applying these results to estimate of the density of functional sequences in the space of all possible amino acid sequences

    The approach taken was to generate collections of randomized mutant sequence variants in a functional TEM-1 variant and “count” the numbers of mutants that retained some measure of activity. Activity was measured by growth of bacteria containing the variants on relatively low levels of ampicillin, a target (or substrate) of TEM-1. (Cells with active TEM-1 can break down the ampicillin and thus survive, whereas cells with mutant TEM-1 variants that can no longer maintain a stably-folded enzyme cannot break down the antibiotic, and this will not grow.)

    Axe anticipated that the native TEM-1 would be rather “resistant” to random mutagenesis, owing to a “buffering effect” contributed by what is probably a robust structural fold.[ IOW, this “resistance” is really a non-tolerance for sequences that won’t form this “robust structural fold,” which means that Axe’s results are actually conservative, rendering Darwinian approaches an even greater opportunity]. This would preclude a proper assessment of the constraints governing low-level function, which in turn are the constraints relevant to the question of the emergence of functional sequences. [What I just wrote is confirmed by this last sentence.] Accordingly, he first isolated, by targeted mutagenesis, a so-called “reference sequence”, a TEM-1 variant that was expected to be much more susceptible to the effects of mutational change. (This is a crucial aspect of the experiment, the ramifications of which are discussed in Section 2.) The variant was identified as a temperature-sensitive enzyme that permitted growth of bacteria on selective (ampicillin-containing) media at a permissive temperature (25 °C), and differs from the wild-type at 22% of the 153 positions. [Doesn’t this mean, then, that you would have to have 22 mutations to take place to get from this “low activity” form of LEM-1 to the wild-type? So, again we’re a long ways off from where evolution needs to get.](“Temperature-sensitive” enzymes lose function after a small change in temperature. Here, the enzyme had some modicum of activity at a lower temperature – 25 °C – but was inactive at elevated temperatures – e.g., 37°C, the temperature at which E. coli is usually grown.)

    This is a fine overview of the experiment.
    You, then, continue:

    There is, however, a fly in the ointment. (Actually, there are many.) Recall that Axe did not work with the native TEM-1 penicillinase, but rather with a variant that had a lower activity. The assay system made this necessary. (Scoring bacteria on antibiotic-containing media isn’t particularly discriminating, and it’s hard to tell is, say, if a wild-type detoxifying enzyme has lost 90% of its activity.) In other words, Axe decided to select a particular part of the “hill” such as that shaded in black in the following illustration (Figure 2):

    But, of course, Axe “had” to do it this way, or, as I noted above in my comments, nothing would have likely happened since the structural fold would not have formed. Your comment to the effect that the “assay” system required Axe to use a “variant” misses the mark. In fact, given your comment about “scoring,” he would have been advised to work with something with ‘more’ activity, say, with the wild type TEM-1.

    You then refer to one of the figures you include. But, as I’ve pointed out before, you haven’t come close to actually visualizing the “base” of the ‘functional’ part of ‘sequence space.’ You’re using ‘two’ dimensions, when the actual dimensions of this space is ‘153’. And, if you want to portray the 153 dimensions as two, and if Axe has determined that the number of functional sequences is 10^-77 of the actual sequence space, then the ‘line’ you show, or ‘peak,’ should be almost invisibly small, with NO “base” whatsoever.
    Pictures can lie.

    In addition, Axe deliberately identified and chose for study a temperature sensitive variant. In altering the enzyme in this way, he molded a variant that would be exquisitely sensitive to mutation. In terms of our illustrations, Axe’s TEM-1 variant is a tiny “hill” with very steep sides, as shown in the following (Figure 3):

    Even “Figure 3” is almost ‘infinitely’ larger than should be depicted.

    Obviously, from these considerations, we can see that assertions that the tiny base of the “hill” in Figure 3 in any way reflects that of a normal enzyme are not appropriate. On this basis alone, we may conclude that the claims of ID proponents vis-à-vis Axe 2004 are exaggerated and wrong.

    On the contrary, your “figure” is what is “exaggerated and wrong.” There should be NO “base,” not even a “tiny base” at the bottom of the figure.

    Axe’s numbers tell us about the apparent isolation of the low-activity variant, but reveal little (nor can it be expected to) about the “isolation” or evolution of TEM-1 penicillinase. (Or any other enzyme, for that matter.)

    As I’ve noted above, evolution would be required to ‘find’ 32 more a.a. mutations (22% of 153) to get to a fully-functioning TEM-1 protein. IOW, the actual protein is even more remotely isolated evolutionarily.

    Of course, there is more. Most naturally-occurring enzymes are not isolated activities as Figure 1 would imply. Something like the next illustration (Figure 4) is a better depiction – distinct activities and enzymes are often derived from common structural and sequence themes.

    How do you get “distinct activities” from “common” structural and sequence themes???

    This expands the base of the “hill” to include those of the neighboring activities; this may be considerable indeed. (In the example of TEM-1 penicillinases, the neighbors would include DD-peptidases; Knox et al, 1996; Adediran et al., 2005.)

    But to “randomly” get to the low-activity TEM-1, 10^77 mutations must occur. Isn’t it obvious that ‘more’ mutations would be needed to get to either of the “neighbors”? I don’t see how this helps your argument.

    However, a relatively recent development, the so-called “mRNA display” technique, allows one to screen random sequences that are much larger (approaching 100 amino acids in length). What is interesting is that the forward approach typically yields a “success rate” in the 10^-10 to 10^-15 range – one usually need screen between 10^10 -> 10^15 random sequences to identify a functional polymer.

    How do you define “success rate”?
    Is it the ability to bind to one, single binding site?

    Why haven’t you called it a “functional protein”?
    Is it because of what you mean by “success rate”?
    Where is your citation? Is it the Cho article?

    This is true even for mRNA display. These numbers are a direct measurement of the proportion of functional sequences in a population of random polymers, and are estimates of the same parameter – density of sequences of minimal function in sequence space – that Axe is after.

    Naturally, the ‘larger’ the sequence space, the more possibilities emerge for ‘binding’ to the ‘target’ sequence. So, the relatively large number of successes should not be surprising.

    1.0^-10 -> 10^-63 (or thereabout): this is the range of estimates of the density of functional sequences in sequence space that can be found in the scientific literature. The caveats given in Section 2 notwithstanding, Axe’s work does not extend or narrow the range.

    While indeed this is true, you have somehow accreted to the revised number for Axe—i.e., ‘your’ 10^-59—(which gives it a value that doesn’t “extend” the range) this number of 1.0×10^-10, without proper identification of neither what the ‘target’ sequence is, nor the ‘success rate’, nor what exactly you mean by ‘functional polymer.’

    As to the Cho article:

    [From: Glen Cho, Anthony D. Keefe, Rihe Liu, David S. Wilson and Jack W. Szostak]

    We present a method that can significantly increase the complexity of protein libraries used for in vitro or in vivo protein selection experiments. Protein libraries are often encoded by chemically synthesized DNA, in which part of the open reading frame is randomized. There are, however, major obstacles associated with the chemical synthesis of long open reading frames, especially those containing random segments. Insertions and deletions that occur during chemical synthesis cause frameshifts, and stop codons in the random region will cause premature termination. These problems can together greatly reduce the number of full-length synthetic genes in the library. We describe a strategy in which smaller segments of the synthetic open reading frame are selected in vitro using mRNA display for the absence of frameshifts and stop codons. These smaller segments are then ligated together to form combinatorial libraries of long uninterrupted open reading frames. This process can increase the number of full-length open reading frames in libraries by up to two orders of magnitude, resulting in protein libraries with complexities of greater than 10^13. We have used this methodology to generate three types of displayed protein library: a completely random sequence library, a library of concatemerized oligopeptide cassettes with a propensity for forming amphipathic a-helical or b-strand structures, and a library based on one of the most common enzymatic scaffolds, the a/b (TIM) barrel.

    Also, from a PubMed article:

    [From “Affinity selection of DNA-binding protein complexes using mRNA display” Seiji Tateyama, Kenichi Horisawa, Hideaki Takashima, Etsuko Miyamoto-Sato, Nobuhide Doi and Hiroshi Yanagawa– Nucleic Acids Research, 2006, Vol. 34, No. 3; doi:10.1093/nar/gnj025:]

    In order to circumvent these difficulties, we focused on a totally in vitro mRNA display technology (11–17), in vitro virus (IVV) (11–14), for the discovery of DNA–protein interactions. In mRNA display, a library of genotype (mRNA)–phenotype (protein) linking molecules (IVV) is constructed in which mRNA is covalently bound to protein through puromycin during cell-free translation. After affinity selection via the protein moiety of the IVV, the mRNA moieties of the selected molecules are amplified by means of RT–PCR. Therefore, even very low-copy number proteins can be identified by iterative affinity selection from a library with high diversity and complexity, routinely in the range of 10^13 members (11–17).

    Let it be noted that this entire field of investigation has to do with finding regulatory sections of the genome, and that what they’re after are those places where proteins ‘bind’ to the DNA. Hence, this is about finding ‘binding sites’ (as noted above), and NOT about finding, or arriving at, a functional “protein.” Functional “proteins” and functional “polymers” should not be confused with one another.

    Finally, Darinian “proponents” always insist on things being “peer-reviewed” before giving something any legitimacy. Why should we consider your Panda’s Thumb post seriously? Shouldn’t you first have your ‘post’ peer-reviewed?

  147. 147
    Zachriel says:

    Mung: Meyer is right about new folds.

    No. Per the quote provided, Meyer is wrong about “bursts of new protein folds”.

  148. 148
    gpuccio says:

    Arthur Hunt:

    Why don’t you just explain what is your reference for 10^10, if it is not Szostak’s paper? So, I will not have to guess any more.

    And however, my criticism of Szostak’s paper had nothing to do with the technique of mRNA display.

  149. 149
    gpuccio says:

    Zachriel:

    “None of your arguments were convincing, though.”

    Why am I not surprised that you were not convinced?

    Thank you for reminding me, however. 🙂

  150. 150
    Mung says:

    Zachriel: Per the quote provided, Meyer is wrong about “bursts of new protein folds”.

    You don’t know if there were “bursts” or not.

    Glad to hear you don’t want to quibble over the actual number of new protein folds.

  151. 151
    Arthur Hunt says:

    Hi vjtorley,

    To continue this discussion and comment on your remarks:

    You said:

    …. Regardless of whether they are justified or not, the methodological criticisms you make of Dr. Axe’s research are certainly substantive, and I think they deserve a fair hearing. Dr. Ann Gauger has contacted me previously and informed me that BioComplexity is happy to publish scientific critiques of Intelligent Design, in addition to scientific articles supporting the case for ID. If you wish to compose a short article outlining your concerns with Dr. Axe’s protein studies, then I would be delighted to forward it to Dr. Axe and Dr. Gauger. I’m sure they’d publish it: after all, they could hardly ignore it.

    That’s not likely to happen. I’ve got two real papers spread all over my desk (we call these “in preparation”), a grant I am reviewing, some grading loose ends, and some new experiments on the docket.

    … if this statement were true, it would stand as a living reproach to biologists all around the world. 10^-10 to 10^-63 is an uncertainty spanning 53 orders of magnitude – and you’re telling me that after 11 years of research, biologists still haven’t succeeded in narrowing that estimate?!?! That’s disgraceful. Someone needs to get off their lazy backsides.

    My comment was more about the fact that the value of Axe’s contributions to the field haven’t changed much in 11 years. Sorry for being cryptic in this regard.

    As far as what you think is sloth on the part of the research community, you should appreciate that pushing this subject beyond the status I depict in my essay is no simple matter. The only way I can think of to make progress is to be able to computationally predict, with very high accuracy, the possible activities of bajillions of randomly-selected sequences, all from first principle. This isn’t feasible at this time (although, in keeping with the tenor of your remark, one has to wonder why the computer math whizzes associated with the Discovery Institute and ID in general haven’t already accomplished this. They should get off their lazy behinds and start doing some real research.)

    Also, to give you a sense of the scope of the problem when it comes to experiment, recall that Axe did his calculation by using a geometric average of the results of four selections. If you take the same results he used to get the average and estimate a 95% confidence interval for the prevalence of function in sequence space, this interval spans many, many orders of magnitude more than the one you are griping about here (from a ratio of function/total sequence space of essentially 1 to essentially 0). So, rather than castigating the larger biology community, maybe you need to be criticizing Axe for giving us results that, properly evaluated, mean precisely nothing (at least when it comes to the question ID proponents are interested in).

    Second, what kind of proteins are we talking about here? In particular, how many amino acids? As biophysicist Dr. Cornelius Hunter has previously pointed out (see my post, The dirty dozen: Twelve fallacies evolutionists make when arguing about the origin of life), the larger proteins (150+ amino acids) appear to be needed for all known forms of life, and there are still no obvious gradual pathways to forming these proteins.

    This matter is quite irrelevant to that of the prevalence (or lack thereof) of function in sequence space.

    While I have your ear, I would ask if you would care to comment on the disconnect between history (portrayed by the SCLB epidemic I mentioned above) and calculations bandied about by Axe, Behe, and other ID proponents.

  152. 152
    Zachriel says:

    Mung: You don’t know if there were “bursts” or not.

    Gpuccio cited Yang & Bourne which found only 17 new domains at the root of bilateria, but inherited thousands.

  153. 153
    Mung says:

    So that’s one burst. Any reason to think it’s the only one?

  154. 154
    Zachriel says:

    Mung: So that’s one burst. Any reason to think it’s the only one?

    Seventeen out of thousands doesn’t meet the definition of a burst, to break open in a sudden and violent way.

  155. 155
    vjtorley says:

    Hi Arthur Hunt,

    I’ve done a little reading about Southern Corn Leaf Blight. You seem to be arguing that random shuffling created a new gene from scratch, with no antecedents. I can’t find anything in the literature which explicitly says that.

    You also claim that cmsT was probably developed over a 20 year period (how do we know it isn’t older than that?) and that T-urf13 consists of at least three “CCCs”. If that’s true, then that’s an argument against Behe’s work, but not Axe’s.

    By the way, here’s a recent paper which discusses SCLB (it’s too technical for me to grasp, but I’m sure you’ll readily understand it):

    http://www.sciencedirect.com/s.....7X15000272

    Since you are currently very busy, I shall communicate your comments to Drs. Axe and/or Gauger, and await a reply from them. Cheers.

  156. 156
    Mung says:

    …metazoan multicellularity is an exclusive feature of animals and is characterized by embryogenesis, whereby a single cell (the zygote) develops into numerous differentiated cells and tissue types.

    The development of metazoan multicellularity is one of the ‘major transitions‘ of evolution, a consequence of which has been a major increase in the level of biological complexity.

    The Choanoflagellates: Evolution, Biology and Ecology

    Well shucks. Looks like Meyer was right again. Those silly DI people.

  157. 157
  158. 158
    Alicia Cartelli says:

    Wow look at Mungy and his eBook searches!

  159. 159
    Mung says:

    Each animal cell type selectively expresses a unique set of proteins from a comprehensive Ca2+ signalling ‘toolkit’ which allows them to transduce appropriate extracellular stimuli … into spatio-temporal Ca2+ signals.

    The Choanoflagellates: Evolution, Biology and Ecology

    Apparently Meyer isn’t so dumb after all.

  160. 160
    Mung says:

    Alicia Cartelli: Wow look at Mungy and his eBook searches!

    Hi troll! Jealous?

    Actually, you just motivated me to check to see if that book is even available on google books, and it is. That could save me some typing. Thanks!

    The Choanoflagellates: Evolution, Biology and Ecology

  161. 161
    Alicia Cartelli says:

    Not jealous at all. Let me know what you come up with!

  162. 162
    Mung says:

    Well, most of the Discussion section from Ch. 10 isn’t available, but fortunately most of the missing material is in the sections that are available.

    See if you can figure out what this refers to:

    “…distinctive orthologues of specific metazoan adhesion proteins are rarely found. …the canonical metazoan adhesion protein architectures probably evolved after divergence of the two lineages.”

  163. 163
    Alicia Cartelli says:

    So a protein fold diverged after the metazoan lineage? Congrats!…

  164. 164
    Mung says:

    You get an F for even suggesting such a thing.

  165. 165
    RexTugwell says:

    Well it seems the Darwinists have the mystery of the Cambrian Explosion all figured out; what with all this talk of genes, proteins and folds. Unfortunately the only thing worse than beating a dead horse is beating the wrong dead horse. Matzke was smart to avoid embryological development in his off-the-cuff (now there’s a howler for you) review.

    The neo-Darwinian mechanism has failed to explain the generation of new genes and proteins needed for building the new animal forms that arose in the Cambrian explosion. But even if mutation and selection could generate fundamentally new genes and proteins, a more formidable problem remains. To build a new animal and establish its body plan, proteins need to be organized into higher-level structures. In other words, once new proteins arise, something must arrange them to play their parts in distinctive cell types. These distinctive cell types must, in turn, be organized to form distinctive tissues, organs, and body plans. This process of organization occurs during embryological development. Thus, to explain how animals are actually built from smaller protein components, scientists must understand the process of embryological development.

    Meyer, Stephen C. (2013-06-18). Darwin’s Doubt: The Explosive Origin of Animal Life and the Case for Intelligent Design (Kindle Locations 4817-4822).

    Protein folds only explain so much. New body plans is where the rubber meets the road.

    I continue to be amused at the dismissive attitude with which our Darwinist friends have toward Meyer, ID and UD. Are you sure you didn’t mean to say obsessive, Nick?

  166. 166
    Arthur Hunt says:

    Two brief notes for you, PaV.

    First, I don’t think you understand the rationale for the use of crippled enzymes. Try as I might, it would seem as if I have confused you. You need to read Axe’s paper – it agrees with my representation and claims, and Axe relayed to me some time ago that my explanation of the rationale was correct.

    Second, the issue here is the enumeration of functional sequences in sequence space. Full stop. Period. The OOL, evolutionary optimization, and other topics are not relevant to this (although they do provide food for thought along other lines).

  167. 167
    Mung says:

    Arthur Hunt: Second, the issue here is the enumeration of functional sequences in sequence space.

    Unfortunately, Nick Matzke thinks that it is the number of functional sequences which determines the size of amino acid sequence space.

  168. 168
    PaV says:

    Arthur Hunt:

    Two brief notes for you, PaV.

    First, I don’t think you understand the rationale for the use of crippled enzymes. Try as I might, it would seem as if I have confused you. You need to read Axe’s paper – it agrees with my representation and claims, and Axe relayed to me some time ago that my explanation of the rationale was correct.

    Arthur, I didn’t say that you misrepresented Axe in the least. In fact, I said just the opposite. After quoting you analysis of Axe’s experiment almost in full, I then added: “This is a fine overview of the experiment.”

    I have no problem whatsoever with your analysis of the experimental methods and results. The problem is with the interpretation.

    The ‘figures’ you include, where did they come from? Certainly not Axe’s paper. I’m sure you got them off of the internet somewhere. Well, they’re misleading, not only because we’re dealing with 153 dimensions—since there are 153 a.a.s and hence 153 variables. But, of course, we can simplify this into two dimensions since we can understand 2D space.

    My main point as regards the ‘figures’ is that they are not anywhere near the reality of what is being dealt with. The ‘peaks,’ in reality, would be so thin as to disappear. This would make the ‘base’ of the ‘peak,’ which in Figure 2 or 3 is shown with a black 2D space, would also be invisible. IOW, the ‘landscapes’ you’re showing distort the true reality of what we’re dealing with here. (Plato said beware of ‘art’!) [But not “arthur”] 🙂

    Now, you might say: “Well, it doesn’t really matter what the figure looks like, nor how big the ‘space’ is, what’s important is that we’re not dealing with the actual TEM-1 domain, but with a ‘TEM-1 variant.’ Hence, this does not really apply to the large domain of the TEM-1 protein. Further, given the ‘low-activity’ of this ‘variant,’ the assay method (scoring method) would likely hide some positive, functional mutants of the ‘variant,’ thus making it more rare.”

    Well, let me answer this charge using your own words (I paraphrase here): “Axe hasn’t extended the range of improbabilities.”

    It could be argued that he has. But leaving that argument aside, his numbers, at minimum, fall into a range that has been determined by others. So, if Axe hasn’t “extended” the range, but falls within the range of other experimenters, then what’s the problem?

    It’s not as if Axe has performed some experiment showing that the probability of mutating your way to function is much more rare than thought. So, why attack Axe?

    This is from Axe’s abstract: Combined with the estimated prevalence of plausible hydropathic patterns (for any fold) and of relevant folds for particular functions, this implies the overall prevalence of sequences performing a specific function by any domain-sized fold may be as low as 1 in 1077, adding to the body of evidence that functional folds require highly extraordinary sequences. [My empahsis]

    Further, this is from a 2013 overview of enzymology:

    The factors that influence biological catalysis have been explored but not all aspects are yet understood in their entirety (Fersht, 1999). The design of new enzymes is built upon the premise that we do understand things well enough to create protein catalysts without the aid of evolution. Pauling (1948) proposed that enzymes complement transition states (TSs) similar to the way that antibodies complement and bind antigens. Over the decades, the view was augmented to include the idea of covalent catalysis and a modification of the reaction mechanisms from what it is in solution to account for the up to 10^23 acceleration that occurs with some of the most proficient enzyme catalysts (Zhang & Houk, 2005). It might be thought that screening of proteins cold find potential catalysts that could then be subjected to directed evolution to produce efficient catalysts (Jackel et al., 2008; Zhao, 2007). However, various estimates have been made which show that the probability of finding an active catalyst for an arbitrary reaction is vanishingly small (Axe, 2004; Taylor, Kast & Hilvert, 2001).

    From: Methods in Enzymology, Vol 523 “Methods in Protein Design,” ed. Amy E. Keating; Academic Press (imprint of Elsevier) 2013

    Axe’s numbers are not only not a problem, they’re accepted by mainline enzymologists.

    Really, the only number in your Panda’s Thumb post that is a problem is your very own, 1 in 10^13.

    As I noted in my last post, you’ve used experiments that are searching for a simple binding site between any protein and any portion of DNA as a proxy for randomized protein sequences searching for enzymatic function. They’re not the same. And you’ve ‘muddied the waters’ with your 1 in 10^13 figure. I thought I demonstrated that rather clearly.

    BTW, using your method of arriving at probabilities, 1 x 10^-13 is equal to (.83)^153. This means that over 80% of amino acids will do when constructing a structural fold. How can this be? What kind of specificity could you have in these folds; and, it is this very specificity that is needed for function to take place in the cell.

    This is, of course, leaves aside the whole problem of comparing DNA-protein binding sequences to structural fold-forming sequences (which I pointed out in my last post); something we ought not to do.

    Second, the issue here is the enumeration of functional sequences in sequence space. Full stop. Period. The OOL, evolutionary optimization, and other topics are not relevant to this (although they do provide food for thought along other lines).

    Let me include a quote from a 2011 discussion of your paper by “JonathanM”:

    Axe’s research set out with the initiative to ascertain the prevalence of sequence variants with a particular hydropathic signature which could form a functional structure [i.e., a ‘fold,’ PaV] out of the space of combinatorial possibilities. Hunt tells us that “Axe deliberately identified and chose for study a temperature sensitive variant. In altering the enzyme in this way, he molded a variant that would be exquisitely sensitive to mutation.” And, indeed, Axe did begin with an extremely weak (temperature sensitive) variant, entailing that an evolving new fold would be expected to be poorly functional. And why would Axe do this? Because he sought to detect variants operating at the lowest level — the threshold, if you will — of detectability.

    So, “the issue here is [NOT] the enumeration of functional sequences in sequence space,” but, rather, sequence spaces that have the ability to form a “functional structure”=”fold”. He uses, as JonathanM points out, the ‘variant’ so that he can find function at the lowest of levels (otherwise evolution won’t work.).

    I was not bringing up either “OOL” or “evolutionary optimization.” You suggested in your Panda’s Thumb post, that somehow the TEM-1 variant could be related—functionally, I suppose—to other proteins. I was merely pointing out that the ‘variant’ must surely be closer in sequence space to the wild-type TEM-1 than it would be to other proteins; otherwise, it would be a ‘variant’ of those proteins!! So, the ‘variant’ must be ‘farther away’ than it is to TEM-1.

    And how far away is it from TEM-1? It’s off by 30 amino acids.

    What are the odds of getting these correct mutations—i.e., not deleteriously mutating away from the wild-type, which is how the ‘variant’ must have come about—for the ‘variant’ to travel to wild-type?:

    (1/22 amino acids)^30 x [1/153 x 1/152 x 1/151 x 1/150 x 1/149 x 1/148 x ….. x 1/123 (correct position along the sequence] = approx 10^-40 (a.a.s) x approx 10^-64=~ 10^-104. Not promising in the “forward” direction, to use your term.

  169. 169
    bill cole says:

    Arthur
    What do you think is the cause of the wide variation of proteins functional space? It seems to me that a stand alone enzyme with one active site would have a much larger window then a nuclear protein that is architected to interact with several different proteins or a protein that is a piece of a multi protein complex like a spliceosome. I appreciate any insight you can provide.

  170. 170
    Mung says:

    PaV: Well, they’re misleading, not only because we’re dealing with 153 dimensions—since there are 153 a.a.s and hence 153 variables.

    Indeed.

    In evolutionary biology, sequence space is a way of representing all possible sequences (for a protein, gene or genome). The sequence space has one dimension per amino acid or nucleotide in the sequence leading to highly dimensional spaces.

    https://en.wikipedia.org/wiki/Sequence_space_%28evolution%29

  171. 171
    Mung says:

    PaV, nicely done. Thank you.

  172. 172
    Mung says:

    “Essential accessory proteins for collagen fibril assembly, collagen propeptidases and lysyl oxidase, are not encoded.”

    Read Section 10.9.6

  173. 173
    Mung says:

    Another hit and run from Nick Matzke?

    IOW, Nick appears and spouts forth some claim or other and when challenged he disappears from sight. Is this a pattern?

  174. 174
    PaV says:

    Mung:

    I just try to understand arguments. Obviously, I think Arthur’s argument misses the mark and am trying to point out how and why.

    About the dimensions, I added that since I wanted to be clear about that. Sometimes I presume knowledge when I shouldn’t. Surprisingly, studying physics is sometimes helpful.

    Let’s see what happens next.

    About Nick, I would agree.

  175. 175
    Andre says:

    Nick is a fraud….. an intellectually dishonest fraud.

  176. 176
    Dr JDD says:

    What has already been alluded to here, but does not get nearly enough attention that it deserves, is the fact that the overwhelming majority of proteins do not have a single interacting partner. And in the overwhelming majority of cases, the >1 interacting partners are not redundant nor unnecessary.

    For example, take an enzyme that must catalyse the conversion of a substrate. Misregulation of such processes lead to dire consequences in the cell. Regulation goes beyond the control of the gene expression. Proteins do not work in linear pathways; they do not simply catalyse a reaction that helps the cell and that is that. They are delicately balanced in complex pathways.

    So the problem that evolution must overcome is not simply
    “creating” a new protein that performs a function; rather it must a) fit within the delicate balance that already exists, b) be appropriately regulated and c) not aberrantly bind other proteins that would influence their function
    that could negatively impact on the cell.

    It seems to me that solving the problem of getting a functional protein for a very specific purpose is far more complicated than simply being able to bind and perform that specific function. Being able to even state (truthfully or not) that random assembly of amino acids can produce a functional protein is really only a small part of the actual problem that materialism has yet to be able to even touch on adequately.

  177. 177
    bill cole says:

    Hi Dr JDD
    Thanks for the post. When I was researching cancer paths for clear cell carcinoma, I was listening to a lecture of a researcher at Cornell who had spend 20 years studying the RAK pathway that was implicated in kidney cancer. In 2012 he had identified 5 proteins that were implicated in starting transcription and cell division. In 2013 he had identified 9 additional proteins involved in this cellular pathway. I would conclude from this that the amino acid substitutions available to the RAK protein had been reduced by this discovery.

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