You asserted that its not all drift, which makes no sense unless I was asserting its all drift and denying selection.
You were wrong in your paper when you omitted drift. Drift is very important in understanding the subject of your paper, no?
2 Likes
Footnotes and related sources:
Bibliography
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Footnotes
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
[1.] The Structure of Evolutionary Theory (2002) by Stephen Jay Gould, Chapter 7, section “Synthesis as Hardening”
[2.] Masel, Joanna (25 October 2011). “Genetic drift”. Current Biology. Cambridge, MA: Cell Press. 21 (20): R837–R838. ISSN 0960-9822. PMID 22032182. doi:10.1016/j.cub.2011.08.007.
[3.] Futuyma 1998, Glossary
[4.] Miller 2000, p. 54
[5.] Kimura, Motoo (17 February 1968). “Evolutionary Rate at the Molecular Level”. Nature. London: Nature Publishing Group. 217 (5129): 624–626. ISSN 0028-0836. PMID 5637732. doi:10.1038/217624a0.
[6.] Futuyma 1998, p. 320
[7.] “Sampling Error and Evolution”. Understanding Evolution. University of California, Berkeley. Retrieved 2015-12-01.
[8.] Wahl, Lindi M. (August 2011). “Fixation when N and s Vary: Classic Approaches Give Elegant New Results”. Genetics. Bethesda, MD: Genetics Society of America. 188 (4): 783–785. ISSN 0016-6731. PMC 3176088 Freely accessible. PMID 21828279. doi:10.1534/genetics.111.131748.
[9.] Hartl & Clark 2007, p. 112
[10.] Tian 2008, p. 11
[11.] Charlesworth, Brian (March 2009). “Fundamental concepts in genetics: Effective population size and patterns of molecular evolution and variation”. Nature Reviews Genetics. London: Nature Publishing Group. 10 (3): 195–205. ISSN 1471-0056. PMID 19204717. doi:10.1038/nrg2526.
[12.] Der, Ricky; Epstein, Charles L.; Plotkin, Joshua B. (September 2011). “Generalized population models and the nature of genetic drift”. Theoretical Population Biology. Amsterdam, the Netherlands: Elsevier. 80 (2): 80–99. ISSN 0040-5809. PMID 21718713. doi:10.1016/j.tpb.2011.06.004.
[13.] Li & Graur 1991, p. 28
[14.] Gillespie, John H. (November 2001). “Is the population size of a species relevant to its evolution?”. Evolution. Hoboken, NJ: John Wiley & Sons for the Society for the Study of Evolution. 55 (11): 2161–2169. ISSN 0014-3820. PMID 11794777. doi:10.1111/j.0014-3820.2001.tb00732.x.
[15.] Neher, Richard A.; Shraiman, Boris I. (August 2011). “Genetic Draft and Quasi-Neutrality in Large Facultatively Sexual Populations”. Genetics. Bethesda, MD: Genetics Society of America. 188 (4): 975–996. ISSN 0016-6731. PMC 3176096 Freely accessible. PMID 21625002. doi:10.1534/genetics.111.128876.
[16.] Ewens 2004
[17.] Li & Graur 1991, p. 29
[18.] Barton et al. 2007, p. 417
[19.] Futuyma 1998, p. 300
[20.] Otto, Sarah P.; Whitlock, Michael C. (June 1997). “The Probability of Fixation in Populations of Changing Size” (PDF). Genetics. Bethesda, MD: Genetics Society of America. 146 (2): 723–733. ISSN 0016-6731. PMC 1208011 Freely accessible. PMID 9178020. Retrieved 2015-12-07.
[21.] Cutter, Asher D.; Choi, Jae Young (August 2010). “Natural selection shapes nucleotide polymorphism across the genome of the nematode Caenorhabditis briggsae”. Genome Research. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. 20 (8): 1103–1111. ISSN 1088-9051. PMC 2909573 Freely accessible. PMID 20508143. doi:10.1101/gr.104331.109.
[22.] Hedrick 2005, p. 315
[23.] Li & Graur 1991, p. 33
[24.] Kimura & Ohta 1971
[25.] Masel, Joanna; King, Oliver D.; Maughan, Heather (January 2007). “The Loss of Adaptive Plasticity during Long Periods of Environmental Stasis”. The American Naturalist. Chicago, IL: University of Chicago Press on behalf of the American Society of Naturalists. 169 (1): 38–46. ISSN 0003-0147. PMC 1766558 Freely accessible. PMID 17206583. doi:10.1086/510212.
[26.] “Natural Selection: How Evolution Works”. Actionbioscience. Washington, D.C.: American Institute of Biological Sciences. Retrieved 2009-11-24. An interview with Douglas J. Futuyma. See answer to question: Is natural selection the only mechanism of evolution?
[27.] Cavalli-Sforza, Menozzi & Piazza 1996
[28.] Zimmer 2001
[29.] Golding 1994, p. 46
[30.] Charlesworth, Brian; Morgan, Martin T.; Charlesworth, Deborah (August 1993). “The Effect of Deleterious Mutations on Neutral Molecular Variation” (PDF). Genetics. Bethesda, MD: Genetics Society of America. 134 (4): 1289–1303. ISSN 0016-6731. PMC 1205596 Freely accessible. PMID 8375663. Retrieved 2015-12-09.
[31.] Presgraves, Daven C. (20 September 2005). “Recombination Enhances Protein Adaptation in Drosophila melanogaster”. Current Biology. Cambridge, MA: Cell Press. 15 (18): 1651–1656. ISSN 0960-9822. PMID 16169487. doi:10.1016/j.cub.2005.07.065.
[32.] Nordborg, Magnus; Hu, Tina T.; Ishino, Yoko; et al. (24 May 2005). “The Pattern of Polymorphism in Arabidopsis thaliana”. PLOS Biology. San Francisco, CA: Public Library of Science. 3 (7): e196. ISSN 1545-7885. PMC 1135296 Freely accessible. PMID 15907155. doi:10.1371/journal.pbio.0030196. open access publication – free to read
[33.] Robinson, Richard, ed. (2003). “Population Bottleneck”. Genetics. 3. New York: Macmillan Reference USA. ISBN 0-02-865609-1. LCCN 2002003560. OCLC 614996575. Retrieved 2015-12-14.
[34.] Futuyma 1998, pp. 303–304
[35.] O’Corry-Crowe, Gregory (March 2008). “Climate change and the molecular ecology of arctic marine mammals”. Ecological Applications. Washington, D.C.: Ecological Society of America. 18 (2, Supplement: Arctic Marine Mammals): S56–S76. ISSN 1051-0761. PMID 18494363. doi:10.1890/06-0795.1.
[36.] Cornuet, Jean Marie; Luikart, Gordon (December 1996). “Description and Power Analysis of Two Tests for Detecting Recent Population Bottlenecks from Allele Frequency Data”. Genetics. Bethesda, MD: Genetics Society of America. 144 (4): 2001–2014. ISSN 0016-6731. PMC 1207747 Freely accessible. PMID 8978083.
[37.] Sadava et al. 2008, chpts. 1, 21–33, 52–57
[38.] “Bottlenecks and founder effects”. Understanding Evolution. University of California, Berkeley. Retrieved 2015-12-14.
[39.] Campbell 1996, p. 423
[40.] “Genetic Drift and the Founder Effect”. Evolution Library (Web resource). Evolution. Boston, MA: WGBH Educational Foundation; Clear Blue Sky Productions, Inc. 2001. OCLC 48165595. Retrieved 2009-04-07.
[41.] Wolf, Brodie & Wade 2000
[42.] Hey, Fitch & Ayala 2005
[43.] Howard & Berlocher 1998
[44.] Wright, Sewall (November–December 1929). “The evolution of dominance”. The American Naturalist. Chicago, IL: University of Chicago Press on behalf of the American Society of Naturalists. 63 (689): 556–561. ISSN 0003-0147. JSTOR 2456825. doi:10.1086/280290.
[45.] Wright, Sewall (1955). “Classification of the factors of evolution”. Cold Spring Harbor Symposia on Quantitative Biology. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. 20: 16–24. ISSN 0091-7451. doi:10.1101/SQB.1955.020.01.004. Symposium: “Population Genetics: The Nature and Causes of Genetic Variability in Populations”.
[46.] Stevenson 1991
[47.] Freeman & Herron 2007
[48.] Masel, Joanna (August 2012). “Rethinking Hardy–Weinberg and genetic drift in undergraduate biology”. BioEssays. Hoboken, NJ: John Wiley & Sons. 34 (8): 701–710. ISSN 0265-9247. PMID 22576789. doi:10.1002/bies.201100178.
[49.] Lynch 2007
[50.] Crow, James F. (March 2010). “Wright and Fisher on Inbreeding and Random Drift”. Genetics. Bethesda, MD: Genetics Society of America. 184 (3): 609–611. ISSN 0016-6731. PMC 2845331 Freely accessible. PMID 20332416. doi:10.1534/genetics.109.110023.
[51.] Larson 2004, pp. 221–243
[52.] Stevenson 1991: Quote attributed to William B. Provine in The Origins of Theoretical Population Genetics (1971), p. 162; Chicago: University of Chicago Press.
[53.] Avers 1989
[54.] Gillespie, John H. (June 2000). “Genetic drift in an infinite population. The pseudohitchhiking model”. Genetics. Bethesda, MD: Genetics Society of America. 155 (2): 909–919. ISSN 0016-6731. PMC 1461093 Freely accessible. PMID 10835409.
[quote=“agauger, post:56, topic:36902”]
What fraction of extant proteins are intrinsically disordered? One paper says 2% archaea, 4% eubacteria, and 33% eukaryotes. (Ward et al 2004 JMB). What proportion intrinsically disordered does that translate for the protein universe? I don’t know, and I don’t think anyone else does either. But my guess is that the stably folded proteins are the vast majority of the protein structural universe. [/quote]
I don’t understand this in the way you are using it. Proteins have multiple folds and multiple disordered regions. Most are a combination of the both. The crystallografers omit the disordered parts from their illustrations.
I don’t know why you go from whole proteins to folds back to whole proteins! If a stably folded protein is defined to be 100% folded, they are a small minority of all proteins.
Saying that studies are interesting is not acknowledging them in a scientific way.
Here is a excellent paper on enzyme promiscuity as an example
This single paper is much more deep and more detailed than the Axe paper, no?
[quote=“agauger, post:56, topic:36902”]You can call any study you don’t like, or the act of quoting it, gratuitous speculation. That is neither evidence or argument. The same protein literature you urge on me acknowledges the problem. Otherwise they would not still be asking the questions.
[/quote]English is not my native tongue, but it is clear to me that Stephen did not call the study gratuitous speculation.
You are also omitting thousands of studies on protein design. The protein literature that he urges you to read shows that many enzymes are very promiscuous and that there are many successes in designing proteins to change their specificity as needed. Neither of these are consistent with the generalisation that Axe did from 3 enzymes and 3 substrates. In science, we must deal with all of the evidence, not only cite the evidence that feeds our passion.
Dear Roberto,
You mistake the question Axe’s paper was asking. He was asking how many protein sequences with the same hydrophobic/hydrophilic profile were able to carry out the beta-lactamase function. He was not asking how many functions beta lactamase could carry out. So although the paper about the amino acid changes that affected promiscuity of an alkaline phosphatase superfamily phosphodiesterase is excellent, it is not relevant.
Stably folded proteins have a tertiary structure composed of alpha helices, beta sheets and unstructured loops. I never said they were 100% folded. They can as a rule be crystalized and their three-dimension structure determined, but they may also contain unstructured regions. Other proteins are unstructured to a greater or lesser degree.
Proteins can exist in a trinity of structures: the ordered state, the molten globule
and the random coil. Five examples follow which suggest that native protein
structure can correspond to any of the three states (not just the ordered state) and
that protein function can arise from any of the three states and their transitions.
…disordered regions include
molecular recognition domains, protein folding inhibitors, flexible linkers,
entropic springs, entropic clocks and entropic bristles. Motivated by such
examples of intrinsic disorder, we are studying the relationships between amino
acid sequence and order/disorder, and from this information we are predicting
intrinsic order/disorder from amino acid sequence. The sequence/structure
relationships indicate that disorder is an encoded property, and the predictions
strongly suggest that proteins in nature are much richer in intrinsic disorder than
are those in the Protein Data Bank. Recent predictions on 29 genomes indicate
that proteins from eucaryotes apparently have more intrinsic disorder than those
from either bacteria or archaea, with typically > 30 % of eucaryotic proteins
having disordered regions of length = 50 consecutive residues.
Do you want a literature review? It won’t be helpful.
I will emphasize what I said elsewhere. You mistake the question Axe’s paper was asking. He was asking how many protein sequences with the same hydrophobic/hydrophilic profile were able to carry out the beta-lactamase function. He was not asking how many functions beta lactamase could carry out. Studies of protein promiscuity, while interesting and important in their own right, do not say anything about how many sequences can fold in a particular way and carry out one particular function, in this case the beta lactamase function.
I have acknowledged elsewhere that separate enzymes have been obtained with beta lactamase function but no apparent evolutionary relationship. So it is possible to have more than one fold carry out the same function. But read his abstract and see if that matters for his estimate.
Proteins employ a wide variety of folds to perform their biological
functions. How are these folds first acquired? An important step toward
answering this is to obtain an estimate of the overall prevalence of
sequences adopting functional folds. Since tertiary structure is needed for a
typical enzyme active site to form, one way to obtain this estimate is to
measure the prevalence of sequences supporting a working active site.
Although the immense number of sequence combinations makes wholly
random sampling unfeasible, two key simplifications may provide a
solution. First, given the importance of hydrophobic interactions to protein
folding, it seems likely that the sample space can be restricted to sequences
carrying the hydropathic signature of a known fold. Second, because folds
are stabilized by the cooperative action of many local interactions
distributed throughout the structure, the overall problem of fold
stabilization may be viewed reasonably as a collection of coupled local
problems. This enables the difficulty of the whole problem to be assessed
by assessing the difficulty of several smaller problems. Using these
simplifications, the difficulty of specifying a working b-lactamase domain
is assessed here. An alignment of homologous domain sequences is used to
deduce the pattern of hydropathic constraints along chains that form the
domain fold. Starting with a weakly functional sequence carrying this
signature, clusters of ten side-chains within the fold are replaced randomly,
within the boundaries of the signature, and tested for function. The
prevalence of low-level function in four such experiments indicates that
roughly one in 10E64 signature-consistent sequences forms a working
domain. 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 10E77, adding to the body of
evidence that functional folds require highly extraordinary sequences.
Now I am going to sign off. Our conversation seems to be getting nowhere, and your tone strikes me as hostile. I understand by that that you do not think Doug’s work is worth anything, and that you think I am incompetent or evasive or ignorant or all three. Not a winning recipe for a dialog.
“gratuitous speculation” is a slap in the face from my point of view. I was trying to not be belligerent in return. I made the point that the question of the rarity of function in sequence space is still being actively examined, and that Doug’s (and others) approach was not gratuitously speculative, and neither was the use of his results.
Once again, promiscuity does not address the question. The question is “Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds,” not how many different functions can this fold produce.
I have taken on board all the criticism, and recommended reading from everyone. I wish you all well.
Ann, what is IDs scientific explanation for these phenomena?
- The geologic column.
- The fossil record, in particular finding organisms of increasing complexity, and no pre-Cambrian rabbits.
- Nested hierarchies.
- Cosmic background radiation?
2 Likes
Pretty much the same as yours.
You were speaking evolutionist speak. I was speaking proteinbio chemist speak. Joke. My language was not precise. I skipped over all that stuff about drifting allele frequencies and achieving fixation. Instead I moved right to the point where you actually have a new mutation fixed in the population.(or two or three mutations). If they result in a new function then fine. If not, then by my admittedly Idiosyncratic definition, no new information.
According to Michael Lynch, drift is one of the four forces of evolution. He described his view of things in a paper called the Frailty of the Adaptive Hypothesis, published in PNAS. Good read.
Personally, I don’t give a darn about de-evolution. It’s not a term I use. And this is about the fourth time I’ve said that.
It’s Neme et al., it’s completely central to this discussion, and you have expressed doubt without saying anything at all about the paper. The results do not “remain to be seen”; they are published.
Which means, as I’ve been saying all along, that it is a mistake (at least the first time) to equate folds with function.
I don’t know why you chose to cite that very old paper, but I note with puzzlement that all of the papers you mention in this post are from 2004. (This is the Ward et al. abstract.) There have been hundreds of papers on related topics since then. There have been whole review articles on the specific question of function in intrinsically-disordered proteins and domains. One recent paper addresses the question of why it seems that eukaryotic proteins have far higher amounts of intrinsic disorder (meaning that there are more intrinsically disordered proteins and domains). Their hypothesis is that IBDs are a eukaryotic innovation.
Similarly, there have been hundreds of papers on protein structure in the context of evolution and gene birth, including a very recent paper of huge importance to the topic, discussed in this thread, on which you have had no comment. The pattern of selective citation is impossible to overlook.
The bigger point, though, is that IBDs make the “fold = function” thing obsolete. To claim that Axe’s estimates are estimates of function in the protein universe would have been just dubious in 2004. Now, thirteen long years later, it’s plainly false. No one who knows the protein evolution literature would claim otherwise.
You have expressed an interest in leaving the conversation, and I totally respect that. My own inbox is overflowing, and it may surprise you to learn that I and every other journal editor I know spend a lot of time reading papers rather than, say, rejecting them due to “bias.” I can certainly understand the desire to spend more time reading than on discussing 13-year-old obsolete papers. I will thus let you have the last word. My parting word is this: you have a responsibility to accurately cite the scientific literature, and I also believe you have a responsibility to avoid making unfounded accusations about journals, editors, and fellow scientists. If you want to specifically discuss the recent literature on protein function (including but not limited to Neme and colleagues) or folding, or IBDs, or standards of peer review at elite journals, please let me know. Otherwise I will only re-engage if I see distortions or errors that I think need to be corrected.
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[quote=“agauger, post:64, topic:36902”]
You mistake the question Axe’s paper was asking. He was asking how many protein sequences with the same hydrophobic/hydrophilic profile were able to carry out the beta-lactamase function.[/quote]
I am making no such mistake, Dr Gauger. I know exactly what he was asking. I am challenging his BIG claim
As an ID proponent, I’ve put forward the scientific case for thinking that the thousands of distinct structures that enable protein molecules to perform their specific tasks inside cells cannot have arisen in a Darwinian way. Moreover, the facts of this problem seem to preclude any naturalistic solution, Darwinian or not.
Like Stephen, I say that the work he has done is insignificant to address the BIG question. I say that the work on promiscuity and protein engineering does much more to address the BIG question. OK? Can we agree on what I really say? Whether you agree or no?
I would also modify your claim about the narrow question he was studying to
That’s very interesting!
Now that we have cleared up the confusion about what we are discussing and focussed on the BIG question, whether
the thousands of distinct structures that enable protein molecules to perform their specific tasks inside cells could have arisen in a Darwinian way,
I see that you specifically cited the views of Dan Herschlag on enzyme promiscuity in the introduction as something relevant to your 2011 paper.
http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2011.1/BIO-C.2011.1
Therefore we both are in complete agreement that it is relevant to the BIG question, no?
I argue that Dan Herschlag’s dozens of experimental papers are much deeper and much more significant than the work of you and Axe in the context of the BIG question, what Axe says evolution can not do.
But you quoted the review of promiscuity by the same scientist in the intro of your paper “The Evolutionary Accessibility of New Enzyme Functions”, the BIG question that you put in the title. Why would you quote that paper if it does not address the BIG question, agree or disagree?
[quote=“sfmatheson, post:69, topic:36902”]
Which means, as I’ve been saying all along, that it is a mistake (at least the first time) to equate folds with function.[/quote]
Exactly!
[quote=“sfmatheson, post:69, topic:36902”]I don’t know why you chose to cite that very old paper, but I note with puzzlement that all of the papers you mention in this post are from 2004. (This is the Ward et al. abstract.) There have been hundreds of papers on related topics since then.
[/quote]I think you are underestimate by a factor of >5. 
OK, I will ignore the rest of the badgering and just respond to the above. You quote Doug on the big picture:
As an ID proponent, I’ve put forward the scientific case for thinking that the thousands of distinct structures that enable protein molecules to perform their specific tasks inside cells cannot have arisen in a Darwinian way. Moreover, the facts of this problem seem to preclude any naturalistic solution, Darwinian or not.
That statement refers to the second phase of our work. Doug’s research focused first on the problem of the rarity of protein folds (Axe 2004), and then we focussed on the difficulty of recruitment of proteins to new function,when they had either with no shared activity or were promiscuous (the paper you cited, where Herschlag is referenced, and others) . So yes, I agree promiscuous proteins can be recruited to new functions and can explain some but not all of the diversity we see. However, when it comes to measuring the rarity of functional folds, promiscuous proteins can’t do that.
So i guess I’d say that you have changed the topic from Axe’s 2004 paper to my 2011 paper in order to bring in promiscuity. Moving the goal.
It would take too long and be of no use to respond to the rest.
I’m sure the authors will be glad to know that.
Agreed.
I am assuming this is over my use of the word bias. If it’s about something else, let me know.
There is a persistent myth about science, the myth that scientists and journals and editors are unbiased. They are humans and human institutions. You fight against bias so hard because it creeps in everywhere. I have heard the stories about peer review and grant review. Scientists are human.
Knowing this, and knowing what I do about what the scientific community as a whole thinks of ID, do I expect fair treatment? No.
It appears to me that you are angry about the charge of bias concerning that paper because you think it is a worthless piece of obsolescent junk. Would you respond the same way if it weren’t by Doug Axe? It did pass peer review at JMB, and has been cited 126 times. And no one had any trouble with it until Doug began to be openly ID.
Are all papers from 2004 obsolete?
If you thought the paper was bad you could have just said so, maybe citing some methodological reasons why, other than the fact that it was just one protein. Or you could have argued about its conclusions. We could have had a rational discussion. Instead I have had scorn heaped on me in subtle and not so subtle ways.
Things started out a little rough here, but then began to be respectful. It all fell apart with the mention of Axe 2004.
That’s my last to you and Roberto.
Since you have mentioned four times that you don’t use the term devolution, you probably won’t need to note down that one of the reasons that I.D. supporters get so little respect is because they deal in such terminology as “Devolution”.
Tell me how well it goes for you if you post something on their boards suggesting they should stop using a term like “Devolution”. I’m sure we will all be pretty interested in how much respect they offer you for your time and trouble.
Pardon me, but what ID boards?
2 Likes
You managed to find BioLogos boards… but you know of no blogs or discussion boards that are in favor of Intelligent Design?
[Note: I myself haven’t visited any because I’ve been assured that my views would not be allowed on them. ]
I actually only know of one: Uncommon Descent, but I rarely visit. Are they into Devolution?
PS, if you don’t visit, how do you know that they deal in such terminology?
1 Like
Dembski and McDowell use the term in their book “Understanding Intelligent Design”. Behe uses it, and Evolution News uses it.
OK, I can ask at Evolution News. The book and Behe I have no influence over. Just to be clear, the reason you dislike the term is because change of any kind is evolution–eyeless fish, legless snakes all evolved?