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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.”

Comments
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.bill cole
January 1, 2016
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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.Dr JDD
January 1, 2016
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Nick is a fraud..... an intellectually dishonest fraud.Andre
December 31, 2015
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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.PaV
December 31, 2015
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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?Mung
December 31, 2015
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"Essential accessory proteins for collagen fibril assembly, collagen propeptidases and lysyl oxidase, are not encoded." Read Section 10.9.6Mung
December 31, 2015
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PaV, nicely done. Thank you.Mung
December 31, 2015
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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
Mung
December 31, 2015
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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.bill cole
December 31, 2015
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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.PaV
December 31, 2015
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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.Mung
December 31, 2015
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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).Arthur Hunt
December 31, 2015
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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?RexTugwell
December 31, 2015
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You get an F for even suggesting such a thing.Mung
December 31, 2015
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So a protein fold diverged after the metazoan lineage? Congrats!...Alicia Cartelli
December 30, 2015
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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."Mung
December 30, 2015
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Not jealous at all. Let me know what you come up with!Alicia Cartelli
December 30, 2015
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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 EcologyMung
December 30, 2015
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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.Mung
December 30, 2015
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Wow look at Mungy and his eBook searches!Alicia Cartelli
December 30, 2015
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Evolution of Extracellular MatrixMung
December 30, 2015
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...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.Mung
December 30, 2015
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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/science/article/pii/S1658077X15000272 Since you are currently very busy, I shall communicate your comments to Drs. Axe and/or Gauger, and await a reply from them. Cheers.vjtorley
December 30, 2015
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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.Zachriel
December 30, 2015
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So that's one burst. Any reason to think it's the only one?Mung
December 30, 2015
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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.Zachriel
December 30, 2015
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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.Arthur Hunt
December 30, 2015
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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.Mung
December 30, 2015
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Zachriel: "None of your arguments were convincing, though." Why am I not surprised that you were not convinced? Thank you for reminding me, however. :)gpuccio
December 30, 2015
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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.gpuccio
December 30, 2015
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