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Average child has 60 genetic mutations?

/Genome Research Limited

From “We Are All Mutants: First Direct Whole-Genome Measure of Human Mutation Predicts 60 New Mutations in Each of Us,” (ScienceDaily, June 12, 2011), a study involving four adults and one child, we learn:

Each one of us receives approximately 60 new mutations in our genome from our parents. This striking value is reported in the first-ever direct measure of new mutations coming from mother and father in whole human genomes.[ ... ]

Mutations that occur in sperm or egg cells will be ‘new’ mutations not seen in our parents.
Although most of our variety comes from reshuffling of genes from our parents, new mutations are the ultimate source from which new variation is drawn. Finding new mutations is extremely technically challenging as, on average, only 1 in every 100 million letters of DNA is altered each generation.

A surprise was the considerable variation in families, as to whether most mutations arose from the father or the mother. In theory, the father was favoured as a source of mutations because of “ the additional number of times that the genome needs to be copied to make a sperm, as opposed to an egg.”

Assuming the results hold up, what would they suggest about human evolution?

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83 Responses to Average child has 60 genetic mutations?

  1. 1
    Elizabeth Liddle

    That there is no shortage of new alleles for natural selection to select?

    But we’ve known for a long time that each of us has tens, if not hundreds of de-novo mutations. I’m a little surprised it’s as low as 60.

  2. Is anyone familiar with “Genetic Entropy” by Dr. J.C. Sanford. If so – think he may be on to something?

  3. 3
    Elizabeth Liddle

    Yes, I’m familiar with it. No, I don’t think “he’s on to something”, although some of what he says is true.

  4. That there is no shortage of new alleles for natural selection to select?

    Um, no. That would be incorrect.

    1. most of our variety comes from reshuffling of genes from our parents

    2. Finding new mutations is extremely technically challenging as, on average, only 1 in every 100 million letters of DNA is altered each generation.

    3. If only 1 in ever 100 million “letters” of DNA is altered, what do you suppose the probability is that it takes place in:

    3a. An allele.

    3b. That has an effect noticeable for selection to choose

  5. Personally, I found “Genetic Entropy” by Dr. J.C. Sanford quite compelling. He makes a very good case that the genomes of all species gradually degrade, as mutations slowly accumulate. Using the principles of population genetics, he argues that most of these mutations are unfavorable but cannot be selected out because their negative effect is too weak. However, as they continue to accumulate over the course of generation after generation, the cumulative effect is that the genomes degrade to the point where the species becomes no longer viable. This is an excellent explanation for why the vast majority of species that have existed on earth have become extinct.

    It’s also one of the three major nails in Darwinism’s coffin, since it implies that a given species cannot be the basis for future species, since each would inherit the degraded genome of the progenitor species, and so would die out all the quicker. If his argument is correct, then there must have been innumerable infusions of new “perfect” genomes (new species) from some source external to biological organisms throughout the history of life on this planet.

    In case you are wondering what the other two nails are, they are 1) the fact that random mutation and natural selection are mathematically incapable of accounting for the emergence of new complex functional information in multicellular organisms, and 2) the fact that in general it is impossible to make a major modification to an existing complex system incrementally if it is a requirement that the system continue to function after each incremental change. For example, it is impossible to develop a jet fighter by making small incremental changes to some piston engine fighter. You can’t even morph a piston engine into a jet engine, much less the entire aircraft. The new fighter has to be designed and built from the ground up. Likewise, you can’t get a new biological body plan from an existing one in small steps. You have to make many simultaneous changes for the new biological system to function.

  6. 6
    Elizabeth Liddle
    That there is no shortage of new alleles for natural selection to select?

    Um, no. That would be incorrect.

    You may be right. As I said, I thought it was a little low. However, that only counts mutations from the germline – additional mutations occur during recombination, and of course recombination itself can produce brandnew alleles by splicing mid-allele.

    However, we know that polymorphisms exist, so the interesting question is: where do they come from?

    Germline mutations are clearly one source, as are recombination mutations and allele splicing.

    What’s interesting to me, though, is the between-individual variance in mutation rate. That is actually fascinating.

    It suggests at least the possiblity that mutation rate is itself a heritable trait.

    This may be well known, but if so, I didn’t know it before.

    That would be pretty exciting.

  7. 7
    Elizabeth Liddle

    @Bruce David:

    Interesting that you found Genetic Entropy compelling. I didn’t, although I do applaud Sanford for some of the points he makes.

    Personally, I found “Genetic Entropy” by Dr. J.C. Sanford quite compelling. He makes a very good case that the genomes of all species gradually degrade, as mutations slowly accumulate. Using the principles of population genetics, he argues that most of these mutations are unfavorable but cannot be selected out because their negative effect is too weak. However, as they continue to accumulate over the course of generation after generation, the cumulative effect is that the genomes degrade to the point where the species becomes no longer viable. This is an excellent explanation for why the vast majority of species that have existed on earth have become extinct.

    In my view, he bases his case on a serious misreading of the literature he cites (Kondrashov and Kimura especially). He is probably right that as populations dwindle, for whatever reasons, they eventually reach a point where accumulating genetic mess contributes to their eventual extinction (which is why it is so important to maintain genetic genetic variety in threatened species.) But as far as I can see, he simply gets his numbers wrong, and also ignore many factors that counter his case, as well as important data.

    It’s also one of the three major nails in Darwinism’s coffin, since it implies that a given species cannot be the basis for future species, since each would inherit the degraded genome of the progenitor species, and so would die out all the quicker. If his argument is correct, then there must have been innumerable infusions of new “perfect” genomes (new species) from some source external to biological organisms throughout the history of life on this planet.

    Yes, if he was right, it would be :) But I think he is wrong, for a substantial number of reasons.

    I

    n case you are wondering what the other two nails are, they are 1) the fact that random mutation and natural selection are mathematically incapable of accounting for the emergence of new complex functional information in multicellular organisms,

    Well, I disagree that that is a “fact” and as a hypothesis I think it can be falsified :)

    and 2) the fact that in general it is impossible to make a major modification to an existing complex system incrementally if it is a requirement that the system continue to function after each incremental change. For example, it is impossible to develop a jet fighter by making small incremental changes to some piston engine fighter. You can’t even morph a piston engine into a jet engine, much less the entire aircraft. The new fighter has to be designed and built from the ground up. Likewise, you can’t get a new biological body plan from an existing one in small steps. You have to make many simultaneous changes for the new biological system to function.

    Your “likewise” doesn’t follow. There are lots of reasons to think that biological body plans differ from jet fighter body plans in precisely the ways that enable it to be adjusted stepwise.

    Indeed the very fact that a single body grows shows that developmentally, stepwise changes are a feature of biology. This is not true of jet-fighters.

    And thus, unlike with a jet-fighter, if you slightly adjust the size of the growth-steps, or their direction, or the signals that govern cell differentiation, then you will get a different, but functioning, body.

    Remember that all living things start as a single cell, that serially divides, the daughter cells gradually differentiating from the ancestral cell.

    There is simply no analog between this process and the process of building (or designing) a jet fighter.

  8. Funny Elizabeth that you never present any actual evidence to counter the principle of Genetic Entropy, but merely your ‘interpretation”.

  9. 9
    Elizabeth Liddle

    The main evidence, ba77, is that plenty of species are thriving.

    If Genetic Entropy was true, all populations would be decreasing. They aren’t.

  10. Elizabeth Liddle, and exactly what part of ‘species are (currently) thriving’ violates the fact of top down design??? ,,, You cannot prove Genetic Entropy wrong by claiming the very point being debated has been proven. i.e. material processes have NEVER been observed generating functional information, yet intelligence does!!! Once again it is sheer intellectual dishonesty for you to be so biased in the way you accept evidence!!1

    EXPELLED – Natural Selection And Genetic Mutations – video
    http://www.metacafe.com/watch/4036840

    “…but Natural Selection reduces genetic information and we know this from all the Genetic Population studies that we have…”
    Maciej Marian Giertych – Population Geneticist – member of the European Parliament – EXPELLED

    This following study is very interesting for the researcher surveyed 130 DNA-based evolutionary trees to see if the results matched what ‘natural selection’ predicted for speciation and found:

    Accidental origins: Where species come from – March 2010
    Excerpt: If speciation results from natural selection via many small changes, you would expect the branch lengths to fit a bell-shaped curve.,,, Instead, Pagel’s team found that in 78 per cent of the trees, the best fit for the branch length distribution was another familiar curve, known as the exponential distribution. Like the bell curve, the exponential has a straightforward explanation – but it is a disquieting one for evolutionary biologists. The exponential is the pattern you get when you are waiting for some single, infrequent event to happen.,,,To Pagel, the implications for speciation are clear: “It isn’t the accumulation of events that causes a speciation, it’s single, rare events falling out of the sky, so to speak.”
    http://www.newscientist.com/ar.....tml?page=2

    ReMine’s The Biotic Message – chapters on Natural Selection. (HT; mung)

    Summary

    Inventive natural selection is the distinctive evolutionary mechanism – essential to Darwinian theory. Evolutionists presume it creates new adaptations by somehow traversing the hills and valleys of the fitness terrain. But they do not attempt to defend it as testable science. Rather, for the defense they shift back to the naive version – survival of the fittest. Then they might offer some tautology to help expunge all doubt.

    When challenged, they shift between various formulations They use naive natural selection to convince the public that evolution is simple, testable, and virtually inevitable.

    When opponents point out that such continually uphill evolution is refuted by the data, evolutionists effortlessly shift away from naive natural selection. Then they charge that the opponent has a poor understanding of evolutionary theory.

    In short, evolutionists merely shifted away from criticism, then focused their arguments (and your attention) in a direction that seemed to overcome the criticism. This phenomenon occurs at several levels.

    Biological adaptation by natural selection is not inevitable, nor is the theory scientific. It had merely lent support to the philosophy of naturalism.
    http://www.uncommondescent.com.....ent-384066

    etc… etc..

  11. 11
    Elizabeth Liddle

    The fact that species are thriving means that Sanford is incorrect.

    That’s all.

  12. Elizabeth #9

    The main evidence, ba77, is that plenty of species are thriving.

    If Genetic Entropy was true, all populations would be decreasing. They aren’t.

    Wow, Elizabeth. That is some seriously blatant dogma.

    His argument is that IF Darwinian evolution is all that is at work, genetic meltdown is the inevitable result of all species. And that is assuming you have species in the first place, nevermind how they got there.

    Thriving species is not evidence against Genetic Entropy. If Genetic Entropy is true, then thriving species is evidence that Darwinian evolution is not responsible for the origination of the vast majority of biology.

    Obviously there are thriving species, so either Genetic Entropy is wrong (which not a lot could be inferred from) or Genetic Entropy is right, Darwinism is a relatively minor biological explanatory tool, and there is another explanation for most of what we witness in biology.

    What makes your statement dogmatic is that it assumes that Darwinism is all that has ever occurred in the history of life, no other inputs besides law and chance. Therefore, if a hypothesis implies that Darwinism can’t create life, all that is needed to prove that hypothesis wrong (with your assumption in place) is evidence of the existence of life. And this is exactly what you did. So with your assumptions, the only possible evidence against Darwinism’s life-creating capabilities is a lifeless universe. That obviously is not the case, therefore Darwinism is unfalsifiable. Hence the dogma.

  13. Elizabeth #11, also see my comment #12

  14. uoflcard, very well said! thanks!

  15. Elizabeth Liddle: “Indeed the very fact that a single body grows shows that developmentally, stepwise changes are a feature of biology. This is not true of jet-fighters.

    And thus, unlike with a jet-fighter, if you slightly adjust the size of the growth-steps, or their direction, or the signals that govern cell differentiation, then you will get a different, but functioning, body.

    Remember that all living things start as a single cell, that serially divides, the daughter cells gradually differentiating from the ancestral cell.

    There is simply no analog between this process and the process of building (or designing) a jet fighter.”

    The process of embryological development is not Darwinian evolution, it is the process by which an organism is built in the natural world. Darwinian evolution requires that each incremental step result in a functioning organism. The intermediate steps in embryological development do not result in functioning (that is, viable) organisms. They will not survive on their own until they are ready to hatch or be born.

    This is the crux of the matter. Given a complex system, one can modify it in incremental steps, certainly, but for Darwinian evolution to work, each step must result in a functioning organism (and indeed one that functions in some way “better” than it did before). To evolve an avian lung, in which the air flow is circular, from a bellows lung, for example, involves many changes not only to the macroscopic form of lung itself but also to its microscopic structures. In addition, there must be concomitant changes to the circulatory system, the musculature, and the neurological system which controls it in order for it to work. Michael Denton, in Evolution a Theory in Crisis, essentially laid down the challenge of showing how such a complex system could have arisen by Darwinian incremental steps. So far, to my knowledge, no one has even proposed a possible solution.

    The reason the analogy with the jet fighter holds is that my proposition is a general thesis about any sufficiently complex system, be it an aircraft, computer software, or a biological organism: it is in general impossible to make a major change to a complex system in incremental steps if you include the requirement that the system continue to function after each such step.

  16. it is in general impossible to make a major change to a complex system in incremental steps if you include the requirement that the system continue to function after each such step.

    Tell that to the construction workers building a new subway line in Manhattan.

  17. lastyearon:

    “‘it is in general impossible to make a major change to a complex system in incremental steps if you include the requirement that the system continue to function after each such step.’

    Tell that to the construction workers building a new subway line in Manhattan.”

    The new line is not functional until it is complete. The old system continues to function, but it does not include the new line until it is finished. When the new line is finished, it will be integrated into the existing system all at once. This example thus supports my thesis. The old system will not be modified incrementally, it will be modified by adding all the parts of the new line at the same time, including whatever modifications to the old system will be required for the integration (control systems, computer software, etc.).

  18. Okay, but where is the evidence for your thesis?

    Certainly, incremental design is well-known in software programming.

  19. 19
    Elizabeth Liddle

    uoflcard @ 12

    Wow, Elizabeth. That is some seriously blatant dogma.

    Well, no, it isn’t :)

    His argument is that IF Darwinian evolution is all that is at work, genetic meltdown is the inevitable result of all species. And that is assuming you have species in the first place, nevermind how they got there.

    Thriving species is not evidence against Genetic Entropy. If Genetic Entropy is true, then thriving species is evidence that Darwinian evolution is not responsible for the origination of the vast majority of biology.

    Obviously there are thriving species, so either Genetic Entropy is wrong (which not a lot could be inferred from) or Genetic Entropy is right, Darwinism is a relatively minor biological explanatory tool, and there is another explanation for most of what we witness in biology.

    Well, interestingly, Mung and I had a discussion about what Sanford meant in his book, and I wrote to him and got a very gracious and helpful reply:

    Given our current understanding of the mutation/selection process, there must clearly be a net loss of information over time in all genomes (with the possible exception of extremely small viral DNA genomes, which might escape this problem). This disproves the basic neo-Darwinian paradigm. What do we do with this fact? The most obvious conclusion would be a Biblical view of history, however the alternative would be to hypothesize that there are other forces (natural or supernatural), which help out mutation/selection. I personally hold the first view, but for those who find this too hard to believe, they are forced to choose the second view.

    So Sanford’s view is that Genetic Entropy is indeed happening, although he allows that if it isn’t,it must be being kept at bay by supernatural forces.

    Well, my point is that we can deduce it is not happening because many species are, in fact thriving, and if they were subject to Genetic Entropy, they would not be, so at the least, the second option seems to be more viable than the first.

    However, I do not think the only explanation for this no-show is supernatural intervention. I think the concept itself is wrong, and is based on a misreading of both data and genetic population models.

    But the existence of thriving species seem pretty irrefutable evidence to me that there has been a no-show. We can argue about why :)

    What makes your statement dogmatic is that it assumes that Darwinism is all that has ever occurred in the history of life, no other inputs besides law and chance. Therefore, if a hypothesis implies that Darwinism can’t create life, all that is needed to prove that hypothesis wrong (with your assumption in place) is evidence of the existence of life. And this is exactly what you did. So with your assumptions, the only possible evidence against Darwinism’s life-creating capabilities is a lifeless universe. That obviously is not the case, therefore Darwinism is unfalsifiable. Hence the dogma.

    Well, to discuss that would be a serious derail from the topic of the OP, although it relates to some conversations I seem to be having on some other threads, so maybe I’ll see you there :)

    Cheers,

    Lizzie.

  20. and blindly Elizabeth restates dogma;

    Elizabeth, to counter Genetic Entropy could you possibly have to provide scientific evidence that mutations are not overwhelmingly detrimental and spreading unabated throughout genomes??? As even this very OP suggests!!! Instead of merely asserting that it isn’t so??? Denial ain’t a river and Egypt, and you ain’t Cleopatra to decree things to be as you wish instead of as they actually are!!!

  21. Elizabeth:

    Well, interestingly, Mung and I had a discussion about what Sanford meant in his book, and I wrote to him and got a very gracious and helpful reply:

    But, unfortunately, you failed to resolve the matter in dispute, which was whether it was the thesis of his book that humans were created perfect approx 10,000 years ago, etc.

    From his response, I would say that at best that is a corollary, rather than the thesis of the book.

  22. So Sanford’s view is that Genetic Entropy is indeed happening, although he allows that if it isn’t, it must be being kept at bay by supernatural forces.

    This appears to be a bald-faced lie.

    You just quoted Sanford as having written:

    …the alternative would be to hypothesize that there are other forces (natural or supernatural), which help out mutation/selection.

  23. 23
    Elizabeth Liddle

    No, simply an error.

    If it was a lie, I’d scarcely have quoted Sanford directly would I?

    Anyway I apologise for the error. I tend to copy and paste direct quotes wherever possible so such errors are minimized, and fortunately, you were able to catch it. Thank you.

    I think there are natural forces that keep it at by (epistasis being one) but I also think the the threat itself is much more limited than Sanford suggests (and indeed, IMO, than his sources suggest).

    Mung, I do appreciate that I am a guest in this community, and that some suspicion is warranted,given that my views are not those of the majority here. But I think I have shown by now that I do not lie (or tell deliberate untruths, which is what a lie is), and that when I make an error, I readily acknowledge the correction.

    I am certainly prone to errors, but I do not lie.

  24. 24
    Elizabeth Liddle

    Mung wrote:

    But, unfortunately, you failed to resolve the matter in dispute, which was whether it was the thesis of his book that humans were created perfect approx 10,000 years ago, etc.

    From his response, I would say that at best that is a corollary, rather than the thesis of the book.

    I am happy to substitute the word corollary.

  25. 25
    Elizabeth Liddle

    bornagain77:

    I have simply read the papers quoted in the OP.

    I’m not “in denial” – I’m simply reporting what they found. It’s a shame they are behind a paywall, but fortunately the abstracts are online, and the content is fairly clear from the abstracts.

  26. 26
    Elizabeth Liddle

    Bruce David @ 15

    The process of embryological development is not Darwinian evolution, it is the process by which an organism is built in the natural world.

    Yes, I know that embryological development is not Darwinian evolution; however the two are extremely closely linked, and must be, as the genes that control development are inherited.

    Darwinian evolution requires that each incremental step result in a functioning organism. The intermediate steps in embryological development do not result in functioning (that is, viable) organisms. They will not survive on their own until they are ready to hatch or be born.

    This is not always true, and it is also a somewhat narrow view of development. More to the point, it’s not terribly relevant to the point I was making! Which is that at all stages of an organism’s life it has to function as an organism (whether “on its own” or not), whereas a jet fighter does not have to function at all until it is ready for use. This means that the “design” (with or without scare quotes) of a living organism has to ensure that it is viable during the assembly process itself. And so, rather than bits being bolted on as required, development involves the differential expression of genes that result in the differentiation of cells and the deformation of the developing organism into intermediate morphologies.

    So any account of the way that genes account for development has to account for this step-wise expression in response to cell signalling, in other words for the way that genes are switched on and off throughout development (and indeed throughout life). So the entire functioning of an organism is much more, well, organic than a human-built artefact, so that a slight tweak to a regulatory gene here, and a slight tweak to a protein there can have smooth, but sometimes substantial, effects on the developing and functioning organism.

    Biological things, unlike human engineered things, grow, develop and breed, remaining viable at all times despite all these processes being step-wise. Biological processes lend themselves to this, while human engineering doesn’t, which is why I find the argument that what is true in the one must be true in the other unpersuasive :)

    Anyway, nice to talk to you.

    Cheers

    Lizzie

  27. Elizabeth, you never present any real evidence for your position, as uoflcard so clearly called you on. But when real evidence is presented against you you just deny that it matters. THAT Elizabeth IS DENIALISM!!!

    notes:

    the slow accumulation of ‘slightly detrimental mutations’ in humans, that is ‘slightly
    detrimental mutations’ which are far below the power of natural selection to remove from our genomes, is revealed by this following fact:

    “When first cousins marry, their children have a reduction of life expectancy of nearly 10 years. Why is this? It is because inbreeding exposes the genetic mistakes within the genome (slightly detrimental recessive mutations) that have not yet had time to “come to the surface”. Inbreeding is like a sneak preview, or foreshadowing, of where we are going to be genetically as a whole as a species in the future. The reduced life expectancy of inbred children reflects the overall aging of the genome that has accumulated thus far, and reveals the hidden reservoir of genetic damage that have been accumulating in our genomes.”
    Sanford; Genetic Entropy; page 147

    Children of incest
    Abstract: Twenty-nine children of brother-sister or father-daughter matings were studied. Twenty-one were ascertained because of the history of incest, eight because of signs or symptoms in the child. In the first group of 21 children, 12 had abnormalities, which were severe in nine (43%). In one of these the disorder was autosomal recessive. All eight of the group referred with signs or symptoms had abnormalities, three from recessive disorders. The high empiric risk for severe problems in the children of such close consanguineous matings should be borne in mind, as most of these infants are relinquished for adoption.
    http://www.jpeds.com/article/S.....8/abstract

    ,,,The evidence for the detrimental nature of mutations in humans is overwhelming for scientists have already cited over 100,000 mutational disorders.

    Inside the Human Genome: A Case for Non-Intelligent Design – Pg. 57 By John C. Avise
    Excerpt: “Another compilation of gene lesions responsible for inherited diseases is the web-based Human Gene Mutation Database (HGMD). Recent versions of HGMD describe more than 75,000 different disease causing mutations identified to date in Homo-sapiens.”

    I went to the mutation database website cited by John Avise and found:

    HGMD®: Now celebrating our 100,000 mutation milestone!
    http://www.biobase-internation.....mddatabase

    Even if a truly beneficial random mutation/variation event to the DNA ever did occur, ignoring the fact that that the DNA doesn’t solely control encoding for body plans, the ‘beneficial mutation’ would still be of absolutely no use for a Darwinian scenario because the mutation would be swallowed in the vast ocean of slightly detrimental mutations which are far below the culling power of natural selection to remove from a genome. these following studies make this point clear:

    Contamination of the genome by very slightly deleterious mutations:
    why have we not died 100 times over? Kondrashov A.S.
    http://www.ingentaconnect.com/.....4/art00167

    The Frailty of the Darwinian Hypothesis
    “The net effect of genetic drift in such (vertebrate) populations is “to encourage the fixation of mildly deleterious mutations and discourage the promotion of beneficial mutations,”
    http://www.evolutionnews.org/2......html#more

    High genomic deleterious mutation rates in hominids
    Excerpt: Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically (unusually) low. A large number of slightly deleterious mutations may therefore have become fixed in hominid lineages.
    http://www.nature.com/nature/j.....344a0.html

    High Frequency of Cryptic Deleterious Mutations in Caenorhabditis elegans ( Esther K. Davies, Andrew D. Peters, Peter D. Keightley)
    “In fitness assays, only about 4 percent of the deleterious mutations fixed in each line were detectable. The remaining 96 percent, though cryptic, are significant for mutation load…the presence of a large class of mildly deleterious mutations can never be ruled out.”
    http://www.sciencemag.org/cgi/...../5434/1748

    All life eventually succumbs to the effects of Genetic Entropy, but humans are especially vulnerable. As This following study reveals:

    Sanford’s pro-ID thesis supported by PNAS paper, read it and weep, literally – September 2010
    Excerpt: Unfortunately, it has become increasingly clear that most of the mutation load is associated with mutations with very small effects distributed at unpredictable locations over the entire genome, rendering the prospects for long-term management of the human gene pool by genetic counseling highly unlikely for all but perhaps a few hundred key loci underlying debilitating monogenic genetic disorders (such as those focused on in the present study).
    http://www.uncommondescent.com.....literally/

  28. Elizabeth, you state:

    ‘Yes, I know that embryological development is not Darwinian evolution; however the two are extremely closely linked, and must be, as the genes that control development are inherited.’

    ,,,But, contrary to your ‘decree’, the evidence states:

    The mouse is not enough – February 2011
    Excerpt: Richard Behringer, who studies mammalian embryogenesis at the MD Anderson Cancer Center in Texas said, “There is no ‘correct’ system. Each species is unique and uses its own tailored mechanisms to achieve development. By only studying one species (eg, the mouse), naive scientists believe that it represents all mammals.”
    http://www.the-scientist.com/news/display/57986/

    Marsupial Embryos Challenge Common Ancestry – Casey Luskin – audio podcast
    http://intelligentdesign.podom.....3_21-08_00

    A Primer on the Tree of Life (Part 4)
    Excerpt: “In sharks, for example, the gut develops from cells in the roof of the embryonic cavity. In lampreys, the gut develops from cells on the floor of the cavity. And in frogs, the gut develops from cells from both the roof and the floor of the embryonic cavity. This discovery—that homologous structures can be produced by different developmental pathways—contradicts what we would expect to find if all vertebrates share a common ancestor. – Explore Evolution
    http://www.evolutionnews.org/2......html#more

    Neo-Darwinism’s Gene Homology Problem – video
    http://www.youtube.com/watch?v=_6P6bXA50c0

    Icons of Evolution 10th Anniversary: Haeckel’s Embryos – January 2011 – video
    http://www.youtube.com/watch?v=W0kHPw3LaG8

    Haeckel’s Bogus Embryo Drawings – The faked drawings compared to actual pictures
    http://www.newworldencyclopedi.....ogeny2.jpg

    Actual Embryo photos;
    http://www.intelldesign.com/wp.....15;385.jpg

    There is no highly conserved embryonic stage in the vertebrates: – Richardson MK – 1997
    Excerpt: Contrary to recent claims that all vertebrate embryos pass through a stage when they are the same size, we find a greater than 10-fold variation in greatest length at the tailbud stage. Our survey seriously undermines the credibility of Haeckel’s drawings,
    http://www.ncbi.nlm.nih.gov/pubmed/9278154

    Current Textbooks Misuse Embryology to Argue for Evolution – June 2010
    http://www.evolutionnews.org/2.....35751.html

  29. 29
    Elizabeth Liddle

    Well, the thing is, ba77, that I tend to find the evidence you offer as unpersuasive as you find the evidence I offer you!

    So just telling me that I’m in denial, isn’t going to help much, I’m afraid. As I see it, there is persuasive evidence for my position, and I would be “in denial” if I didn’t acknowledge it.

    But I also acknowledge that that evidence does not persuade you, and I appreciate your efforts.

  30. Bull Elizabeth, your evidence that Genetic Entropy is not a real concern, is the same evidence I can use to show that God initially created each lifeform on Earth!!! WEhereas real evidence is simply Denied or rationalized away. You are not fair with the evidence in the least!!!

  31. bornagain77@30:

    Bull Elizabeth…

    Where are the tone police?

  32. Elizabeth Liddle:

    I am certainly prone to errors, but I do not lie.

    Elizabeth. What sort of error was it?

    Did you simply not read what he wrote?

    Are you just so locked into a certain perception of Sanford that you are blinded to what he actually says?

    You misrepresented Sanford, not just once, but twice.

    Not only did he write, natural OR supernatural, but he also clearly stated that he accepts neither of those.

    The most obvious conclusion would be a Biblical view of history, however the alternative would be to hypothesize that there are other forces (natural or supernatural), which help out mutation/selection. I personally hold the first view, but for those who find this too hard to believe, they are forced to choose the second view.

    Seriously.

    He presents two alternative views and says he holds the first, which he calls “a Biblical view of history.”

    I am happy to substitute the word corollary.

    What then do you now say is the thesis of his book?

  33. 33

    Lizzy,

    Re. #26: Well, nice talking with you, too. You may call me Bruce if you like.

    I must say, though, that you have basically sidestepped my point, which is that major modifications to any complex system of whatever nature (be they biological or otherwise) cannot be accomplished through a series small incremental steps if there is a requirement that the system continue to function after each such step. This is because a complex system is composed of many parts that fit together and interact both spatially and temporally in ways that depend on each other. I refer you again to the example I invoked in #15 of the impossibility of evolving an avian lung from a bellows lung. If you try to do this in small steps, the intermediate stages don’t work and would be fatal to the organism. Therefore, if it happened in a Darwinian way, it must have happened all at once (ie., saltationally). However, absent engineering input from an intelligent agent, such an emergence of a radically new organism in one fell swoop is effectively impossible, given the probabilities.

    Regarding the ongoing discussion around Sanford’s book, when you say that Sanford’s thesis is invalidated by the fact that there are “thriving species” alive today, you have again missed the point, which is that EITHER Darwinism is correct OR Sanford is, but not both. If Sanford is correct then this implies that currently “thriving” species were introduced by some means complete with perfect (ie., non-degraded) genomes within the last several million years (the typical length of time that a species exists in the fossil record). We observe them thriving today simply because their genomes have not yet had time to degrade to the point of non-viability. This includes us, by the way. In short, the current existence of thriving species does not, in and of itself, invalidate Sanford.

  34. 34
    Elizabeth Liddle

    Mung, we seem to be having serious communication difficulties here. I accept a substantial portion of the liability but not the full portion; clearly there is a level of distrust on your part of me that will have to be overcome before we can do much better.

    So I will make three points, make of them what you will; I will try to be unambiguous, but may not succeed:

    1. I think Sanford is actually wrong in his analysis that Genetic Entropy is inevitable under evolutionary theory. I think he has misunderstood his sources, and misread the data.

    2. I think (though conceivably I could have misunderstood him) that his own position is that the most likely scenario is that mankind was created perfect in the Garden of Eden a few thousand years ago, and our genomes have been deteriorating inevitably since then.

    3. He offers the alternative that our genomes are not inevitably deteriorating, but that if so, there must be some natural or supernatural force stopping them, because otherwise that’s what the science (including Darwinism) predicts. My position is that science predicts this only in very particular circumstances, and that even there, there are natural forces that tend to stop it happening, so no supernatural prevention system need be invoked or inferred.

    As for the thesis of his book: my reading of it is that our genomes are inevitably deteriorating, hence the title. He does not offer a natural alternative in his book (though he does tell us to put our hope in Jesus Christ). If something is inevitably deteriorating, the corollary is that it started in a much nearer-perfect, if not perfect, state, and the time line he suggests is a few thousand years.

    This conforms with his YEC position, and I see no reason to think it is not the corollary he himself draws, especially as he, as I read it, confirmed it in his email to me.

    If I’ve misunderstood him, so be it.

    You are correct that I overlooked the word “natural” in his email, and I’m encouraged, in a way, that he allows for such a possibility. However, I don’t think it is even required (at least to the extent he implies), as I think his concept of Genetic Entropy is actually an error.

    I think this because I have read the papers he cites and I don’t think they lead to the conclusions he draws.

    In peace

    Lizzie

  35. Elizabeth, since evidence, and even this very OP, has presented actual evidence to you that you are wrong and Genetic Entropy is true, perhaps you would care to present actual evidence (for truly beneficial mutations, genome plasticity and extreme genome management for the overwhelming majority of slightly deleterious mutations that do occur) instead of just your opinion/thinking, that you are not wrong???

  36. 36
    Elizabeth Liddle

    Well, no, ba77, the OP doesn’t provide such evidence.

    It actually suggests that a rather low rate of mutation, although this is probably because it excludes mutations that arise during recombination.

    It says nothing about the distribution of those mutation on the scale of deleterious-beneficial, and, as Mung points out, the number that hit a useful allele may be very small.

    However, we know that large numbers of genes have many polymorphisms, and those must have come from somewhere. The OP suggests one route, together with the interesting possibility that mutation rate itself may be heritable.

    However, if you want evidence for beneficial mutatations, check out the Lenski studies referenced in another recent OP here.

    I’d also point out that we do not know that VSDMs outnumber VSBMs. They may do, but there is no reason to think that VSBMs are particularly rare.

  37. Elizabeth, yes the OP does when taken in context (which you are loathe to do), and as to prime example of your extreme bias in ‘interpretation of evidence’ you state:

    ‘However, if you want evidence for beneficial mutatations, check out the Lenski studies referenced in another recent OP here.’

    HMMM Elizabeth, it seems those 5 ‘beneficial mutations’, when taken singly, are only beneficial in a very select reading of ‘beneficial’;

    Michael Behe’s Quarterly Review of Biology Paper Critiques Richard Lenski’s E. Coli Evolution Experiments – December 2010
    Excerpt: After reviewing the results of Lenski’s research, Behe concludes that the observed adaptive mutations all entail either loss or modification–but not gain–of Functional Coding ElemenTs (FCTs)
    http://www.evolutionnews.org/2.....41221.html

    Lenski’s e-coli – Analysis of Genetic Entropy
    Excerpt: Mutants of E. coli obtained after 20,000 generations at 37°C were less “fit” than the wild-type strain when cultivated at either 20°C or 42°C. Other E. coli mutants obtained after 20,000 generations in medium where glucose was their sole catabolite tended to lose the ability to catabolize other carbohydrates. Such a reduction can be beneficially selected only as long as the organism remains in that constant environment. Ultimately, the genetic effect of these mutations is a loss of a function useful for one type of environment as a trade-off for adaptation to a different environment.
    http://www.answersingenesis.or.....n-bacteria

    Thus Elizabeth you have no evidence for ‘truly beneficial mutations’ in the Lenski study you cited; but to make matters much worse for you, the whole point of the Lenski paper was to point out that the ‘beneficial mutations’, you were hoping to contort to be evidence for your neo-Darwinian worldview, are no longer beneficial, even in the narrow sense, when the mutations are present all together!!!

    Thus Elizabeth even though the evidence is very clear, once again you have severely twisted to meet your ‘Cleopatra’ (Queen of Denial) criteria for being evidence for your position. Truly a rabbit hole of illusion Elizabeth!!!

  38. Elizabeth you state:

    ‘I’d also point out that we do not know that VSDMs outnumber VSBMs. They may do, but there is no reason to think that VSBMs are particularly rare.’

    No Elizabeth, DO NOT use WE!!! YOU DO NOT KNOW!!!

    Mutation Studies, Videos, And Quotes
    http://docs.google.com/Doc?doc.....ZnM5M21mZg

  39. However, we know that large numbers of genes have many polymorphisms…

    Is this something predicted by Darwinian theory?

    Shouldn’t we see the exact opposite of this, if Darwinian theory is correct?

  40. Elizabeth,

    You said in #7, “In my view, he bases his case on a serious misreading of the literature he cites (Kondrashov and Kimura especially)…But as far as I can see, he simply gets his numbers wrong, and also ignore many factors that counter his case, as well as important data.”

    But when Bornagain77 comments, “Funny Elizabeth that you never present any actual evidence to counter the principle of Genetic Entropy, but merely your ‘interpretation’”, you reply, “The main evidence, ba77, is that plenty of species are thriving. If Genetic Entropy was true, all populations would be decreasing. They aren’t.” And a little later, “The fact that species are thriving means that Sanford is incorrect. That’s all.”

    Then when uoflcard in #12 and I in #33 point out that the existence of thriving species does not invalidate Sanford’s thesis, you return in #34 to your original contention, which you sidestepped in response to BA77: “I think Sanford is actually wrong in his analysis that Genetic Entropy is inevitable under evolutionary theory. I think he has misunderstood his sources, and misread the data.”

    Now my reading of Sanford is that he takes known rates of mutation coupled with the ratios of those that are beneficial to those that are harmful along with the proportion of those that are selectable in multicellular organisms (based on the work of population geneticists) and concludes, using those numbers, that the genomes of all multicellular organisms are slowly degrading as mildly harmful mutations accumulate in generation after generation. He also concludes that this accumulation of harmful mutations eventually results in species extinction, a process that takes roughly several million years, the typical length of time that occurs between the introduction of a species into the fossil record and its sudden disappearance.

    If your contention is that Sanford “has misunderstood his sources, and misread the data,” could you please be more specific and tell us exactly what his errors are?

    And BTW, the OP DOES support Sanford’s thesis, since it is well known that the vast majority of genetic mutations are harmful.

  41. … it is well known that the vast majority of genetic mutations are harmful.

    Gah. I wonder where on earth I got the idea that the vast majority of genetic mutations don’t have any effect at all, and therefore are neither beneficial nor harmful.

    I guess I need to read more Sanford!

  42. ‘I wonder where on earth I got the idea that the vast majority of genetic mutations don’t have any effect at all,’

    note:

    Unexpectedly small effects of mutations in bacteria bring new perspectives – November 2010
    Excerpt: Most mutations in the genes of the Salmonella bacterium have a surprisingly small negative impact on bacterial fitness. And this is the case regardless whether they lead to changes in the bacterial proteins or not.,,, using extremely sensitive growth measurements, doctoral candidate Peter Lind showed that most mutations reduced the rate of growth of bacteria by only 0.500 percent. No mutations completely disabled the function of the proteins, and very few had no impact at all. Even more surprising was the fact that mutations that do not change the protein sequence had negative effects similar to those of mutations that led to substitution of amino acids. A possible explanation is that most mutations may have their negative effect by altering mRNA structure, not proteins, as is commonly assumed.
    http://www.physorg.com/news/20.....teria.html

  43. 43
    Elizabeth Liddle

    Mung: it is NOT “well known that the majority of mutations are harmful”. It is fairly well-known that the vast majority of mutations are near-neutral. While there is reason to assume that in a well-adapted population, more of those near-neutral mutations will be deleterious than beneficial, the opposite will tend to be true in a population that is undergoing environmental change.

    This is one of a number of points that Sanford does not consider, and is crucial. In fact he seems to think that the closer you get, from the deleterious end, to neutrality, the more mutations you find (“VSDMs”); then, without any justification, whether by argument or evidence, he assumes a cliff edge with virtually no mutations that are “VSBMs”.

    This is an actual mistake, and his entire argument fails because of it.

  44. Elizabeth you state:

    ‘While there is reason to assume that in a well-adapted population, more of those near-neutral mutations will be deleterious than beneficial, the opposite will tend to be true in a population that is undergoing environmental change.’

    This is a false statement! It is true that in constant environment there have never been observed any mutations that were ‘beneficial’,

    Testing Evolution in the Lab With Biologic Institute’s Ann Gauger – podcast with link to peer-reviewed paper
    Excerpt: Dr. Gauger experimentally tested two-step adaptive paths that should have been within easy reach for bacterial populations. Listen in and learn what Dr. Gauger was surprised to find as she discusses the implications of these experiments for Darwinian evolution. Dr. Gauger’s paper, “Reductive Evolution Can Prevent Populations from Taking Simple Adaptive Paths to High Fitness,”.
    http://intelligentdesign.podom.....4_13-07_00

    Is Antibiotic Resistance evidence for evolution? – ‘The Fitness Test’ – video
    http://www.metacafe.com/watch/3995248

    ,,,yet contrary to the claim of Elizabeth that most mutations will not be slightly detrimental when an environment is ‘stressed’ (changed in her words), the fact is that very few mutations help to generate a beneficial adaptations in a ‘stressed environment’,,,

    Michael Behe, The Edge of Evolution, pg. 162 Swine Flu, Viruses, and the Edge of Evolution
    “Indeed, the work on malaria and AIDS demonstrates that after all possible unintelligent processes in the cell–both ones we’ve discovered so far and ones we haven’t–at best extremely limited benefit, since no such process was able to do much of anything. It’s critical to notice that no artificial limitations were placed on the kinds of mutations or processes the microorganisms could undergo in nature. Nothing–neither point mutation, deletion, insertion, gene duplication, transposition, genome duplication, self-organization nor any other process yet undiscovered–was of much use.”
    http://www.evolutionnews.org/2....._edge.html

    ,,,Moreover these beneficial adaptations all, for the vast majority of times, come at a loss of functional information/complexity.,,,

    “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.(that is a net ‘fitness gain’ within a ‘stressed’ environment i.e. remove the stress from the environment and the parent strain is always more ‘fit’, without several rounds of ‘compensatory mutations’ for the ‘more evolved strain’)
    http://behe.uncommondescent.co.....evolution/

  45. Excerpt: Most mutations in the genes of the Salmonella bacterium have a surprisingly small negative impact on bacterial fitness.

    What percentage of mutations are in the genes?

  46. Mung: it is NOT “well known that the majority of mutations are harmful”. It is fairly well-known that the vast majority of mutations are near-neutral.

    And I thought I had a British sense of humor. :)

    I guess I’ve been fooling myself for a long time.

  47. mung, page 23 of Genetic Entropy

  48. Mung, It is fairly hard to argue for ‘completely neutral’ mutations, for even mutations which ‘do nothing at all’ still require energy to replicate, and thus are a ‘slight burden’

    Experimental Evolution of Gene Duplicates in a Bacterial Plasmid Model
    Excerpt: In a striking contradiction to our model, no such conditions were found. The fitness cost of carrying both plasmids increased dramatically as antibiotic levels were raised, and either the wild-type plasmid was lost or the cells did not grow. This study highlights the importance of the cost of duplicate genes and the quantitative nature of the tradeoff in the evolution of gene duplication through functional divergence. http://www.springerlink.com/co.....4014664w8/

    The Extinction Dynamics of Bacterial Pseudogenes – Kuo and Ochman – August 2010
    Excerpt: “Because all bacterial groups, as well as those Archaea examined, display a mutational pattern that is biased towards deletions and their haploid genomes would be more susceptible to dominant-negative effects that pseudogenes might impart, it is likely that the process of adaptive removal of pseudogenes is pervasive among prokaryotes.”
    http://www.evolutionnews.org/2.....37581.html

    Arriving At Intelligence Through The Corridors Of Reason (Part II) – April 2010
    Excerpt: ,,, since junk DNA would put an unnecessary energetic burden on cells during the process of replication, it stands to reason that it would more likely be eliminated through selective pressures.
    http://www.uncommondescent.com.....n-part-ii/

    How The Junk DNA Hypothesis Has Changed Since 1980 – Richard Sternberg – Oct. 2009 – Excellent Summary
    Excerpt: A surprising finding of ENCODE and other transcriptome projects is that almost every nucleotide of human (and mouse) chromosomes is transcribed in a regulated way.
    http://www.evolutionnews.org/2.....is_ha.html

    Non-coding RNAs and eukaryotic evolution – a personal view – John Mattick – May 2010
    Excerpt: “But you certainly need to have a more complex regulatory framework to get to a more complex organism, and the astounding thing is that the only thing that does scale with complexity – because the number of genes does not – is the extent of the non-protein-coding genome.”
    http://www.ncbi.nlm.nih.gov/pm.....MC2905358/

  49. Getting Over the Code Delusion – From Junk to Living Organism – November 2010
    Excerpt: So what’s going on? These puzzles turn out to be intimately related. As organisms rise on the evolutionary scale, they tend to have more “junk DNA.” Noncoding DNA accounts for some 10 percent of the genome in many one-celled organisms (i.e. 90% of single celled organisms are genetic coding regions), 75 percent in roundworms, and 98 percent in humans. The ironic suspicion became too obvious to ignore: maybe it’s precisely our “junk” that differentiates us from water fleas. Maybe what counts most is not so much the genes themselves as the way they are regulated and expressed. Noncoding DNA could provide the complex regulatory functions that direct genes toward service of the organism’s needs, including its developmental needs.

    That suspicion has now become standard doctrine — though a still much-too-simplistic doctrine if one stops there. For noncoding as well as coding DNA sequences continue unchanged throughout the organism’s entire trajectory of differentiation, from single cell to maturity. Lillie’s point therefore remains: it is hardly possible for an unchanging complex to explain an ordered developmental stream. Constant things cannot by themselves explain dynamic processes.
    http://www.thenewatlantis.com/.....e-delusion

  50. Mung, It is fairly hard to argue for ‘completely neutral’ mutations, for even mutations which ‘do nothing at all’ still require energy to replicate, and thus are a ‘slight burden’

    I guess you got me there BA.

    But let me think.

    What if the mutation occurs as a result of the nucleotide being replicated?

    Point mutations may arise from spontaneous mutations that occur during DNA replication.

    Point mutation

    So it was already being copied anyways, and therefore there was no additional energy burden.

    Thus without more details on your part I find that argument unconvincing, to say the least.

  51. 51

    Elizabeth, you state: “[Sanford] seems to think that the closer you get, from the deleterious end, to neutrality, the more mutations you find (‘VSDMs’); then, without any justification, whether by argument or evidence, he assumes a cliff edge with virtually no mutations that are ‘VSBMs’.”

    This is simply not true.

    p. 24 of the paperback edition: “I have seen estimates of the ratio of deleterious-to-beneficial mutations which range from one thousand to one, up to one million to one. The best estimates seem to be one million to one (Gerrish and Lenski, 1998). The actual rate of beneficial mutations is so extremely low as to thwart any actual measurement (Bataillon, 2000, Elena et al, 1998).”

    On p. 25: “When it was discovered that certain forms of radiation and certain chemicals were powerful mutagenic agents, millions and millions of plants were mutgenized and screened for possible improvements…Vast numbers of mutants were produced and screened, collectively representing many billions of mutation events. A huge number of small, sterile, sick, deformed, aberrant plants were produced. However, from all this effort, almost no meaningful crop improvement resulted. The effort was for the most part an enormous failure. Why did this huge mutation/selection experiment fail…? It was because even with all those billions of mutations, there were no significant new beneficial mutations arising. The notable exceptions prove the point. For example, low phytate corn…The low phytate corn was created by nutagenizing corn, and then selecting for strains wherein the genetic machinery which directs phytic acid production had been damaged. Although the resulting mutant may be desired for a specific agricultural purpose, it was accomplished through net loss of information,…and the loss of biological function. Most of the other examples of successful mutation breeding are found within the area of ornamental plants. Examples of “useful” mutations…include sterility, dwarfing, mottled or variegated foliage, altered color patterns, or misshaped floral organs.

    And on p. 25: Bergman (2004)…did a simple literature search via Biological Abstracts and Medline. He found 453,732 “mutation” hits, but among these only 186 mentioned the word “beneficial” (about 4 in 10,000). When those 186 references were reviewed, almost all the presumed “beneficial mutations” were only beneficial in a very narrow sense — but consistently involved loss-of-function changes (hence loss of information). He was unable to find a single example of a mutation which unambiguously created new information.

    So I repeat my question, exactly how has Sanford “misunderstood his sources, and misread the data”?

  52. Mung, If it is truly a random mutation within a functional sequence, such as a typo in a sentence, then you are clearly moving away from optimal functionality to sub-optimal functionality and are thus ‘slightly detrimental’. If it is ‘sub-functional or non-functional’ energetic burden will increase and decrease fitness thus favoring removal by further mutation/selection.

    Notes;

    Astonishing DNA complexity update
    Excerpt: The untranslated regions (now called UTRs, rather than ‘junk’) are far more important than the translated regions (the genes), as measured by the number of DNA bases appearing in RNA transcripts. Genic regions are transcribed on average in five different overlapping and interleaved ways, while UTRs are transcribed on average in seven different overlapping and interleaved ways. Since there are about 33 times as many bases in UTRs than in genic regions, that makes the ‘junk’ about 50 times more active than the genes.
    http://creation.com/astonishin.....ity-update

    also of interest;

    As former president of the French Academy of Sciences Pierre P. Grasse has stated:

    “What is the use of their unceasing mutations, if they do not change? In sum, the mutations of bacteria and viruses are merely hereditary fluctuations around a median position; a swing to the right, a swing to the left, but no final evolutionary effect.”

    Bacteria ‘Invest’ (Designed) Wisely to Survive Uncertain Times, Scientists Report – Dec. 2009
    Excerpt: Essentially, variability of bacterial cells appears to match the variability in the environment, thereby increasing the chances of bacterial survival,
    http://www.sciencedaily.com/re.....112102.htm

    It is also interesting to note that scientists have actually used a mechanism of ‘excessive mutations’ to help humans in their fight against pathogenic viruses, as the following articles clearly point out:

    GM Crops May Face Genetic Meltdown
    Excerpt: Error catastrophe occurs when high mutation rates give rise to so many deleterious mutations that they make the population go extinct. For example, foot and mouth disease virus treated with mutagens (base analogues fluorouracil and azacytidine) eventually become extinct [1]. Polio virus treated with the mutagenic drug ribavirin similarly went extinct [2].
    http://www.i-sis.org.uk/meltdown.php

    Quasispecies Theory and the Behavior of RNA Viruses – July 2010
    Excerpt: Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. ,,, it has been termed “mutational meltdown.” It is now clear that many RNA viruses replicate near the error threshold. Early studies with VSV showed that chemical mutagens generally reduced viral infectivity, and studies with poliovirus clearly demonstrated that mutagenic nucleoside analogs push viral populations to extinction [40]–[43]. The effect is dramatic—a 4-fold increase in mutation rate resulted in a 95% reduction in viral titer.,,, While mutation-independent activities have also been identified, it is clear that APOBEC-mediated lethal mutagenesis is a critical cellular defense against RNA viruses. The fact that these pathogens replicate close to the error threshold makes them particularly sensitive to slight increases in mutational load.,,,
    http://www.plospathogens.org/a.....01005-g003

    Life Leads the Way to Invention – Feb. 2010
    Excerpt: a cell is 10,000 times more energy-efficient than a transistor. “ In one second, a cell performs about 10 million energy-consuming chemical reactions, which altogether require about one picowatt (one millionth millionth of a watt) of power.” This and other amazing facts lead to an obvious conclusion: inventors ought to look to life for ideas.,,, Essentially, cells may be viewed as circuits that use molecules, ions, proteins and DNA instead of electrons and transistors. That analogy suggests that it should be possible to build electronic chips – what Sarpeshkar calls “cellular chemical computers” – that mimic chemical reactions very efficiently and on a very fast timescale.
    http://creationsafaris.com/cre.....#20100226a

    Also of interest is that a cell apparently seems to be successfully designed along the very stringent guidelines laid out by Landauer’s principle of ‘reversible computation’ in order to achieve such amazing energy efficiency, something man has yet to accomplish in any meaningful way for computers:

    Notes on Landauer’s principle, reversible computation, and Maxwell’s Demon – Charles H. Bennett
    Excerpt: Of course, in practice, almost all data processing is done on macroscopic apparatus, dissipating macroscopic amounts of energy far in excess of what would be required by Landauer’s principle. Nevertheless, some stages of biomolecular information processing, such as transcription of DNA to RNA, appear to be accomplished by chemical reactions that are reversible not only in principle but in practice.,,,,
    http://www.hep.princeton.edu/~.....501_03.pdf

    etc.. etc…

    Well Mung, every measure I can find says that ‘truly random’ single point mutations will be slightly detrimental. Thus you are free to believe whatever you want, but as for myself, I will follow the evidence and it clearly indicates the premise is correct.

  53. Bornagain,

    It’s interesting how you and I switch from being adversaries to allies, depending on the subject matter, don’t you think?

  54. 54
    Elizabeth Liddle

    Bruce:

    You write:

    Elizabeth, you state: “[Sanford] seems to think that the closer you get, from the deleterious end, to neutrality, the more mutations you find (‘VSDMs’); then, without any justification, whether by argument or evidence, he assumes a cliff edge with virtually no mutations that are ‘VSBMs’.”

    This is simply not true.

    Firstly , it is true that he assumes a cliff edge (See Figure 9).

    Secondly, Gerrish and Lenski(1998) are talking about the ratio of observably beneficial mutations to observably deleterious, not “VSBMs” to “VSDMs”, which are, by definition, not observable, and for a well-adapted population (at least of E-coli) their estimate may well be correct. We would certainly expect the distribution of all mutations to have a very long negative (deleterious) tail, and possibly not much of a beneficial tail at all.

    However, the vast majority of mutations will be near-neutral, i.e. not detectably beneficial or deleterious and thus “invisible to selection”. Sanford agrees, indeed it is one of the major themes of his book. But he extrapolates from the perfectly good evidence that DMs vastly outnumber BMs (which he doesn’t worry about because, as DMs are, by definition “visible to selection” they won’t accumulate) to assuming that the same ratio applies to VSDMs and VSBMs. This assumption is completely unjustified, and there is no evidence for it, nor any theoretical reason to believe it (quite the reverse).

    In a well-adapted population, of course, it is true that there will be more VSDMs than VSBMs because the mode of the distribution will have moved towards the optimum. However, change the environment, and your mode will be shunted to the left, whereupon selection kicks in (because now some VSDMs become SDMs and SDMs become DMs, and similarly, what were only VSBMs or even VSDMs now become SBMs or BMs) and the mode tracks rightward again.

    And that is Sanford’s other error – to forget that whether a mutation is “deleterious” or “beneficial” is not an absolute attribute of the mutation, but is a function of the mutation within its environment.

    And then there is epistasis, but maybe we’ll leave that for another time :)

    Cheers

    Lizzie

  55. 55
    Elizabeth Liddle

    On closer reading, it may be that Gerrish and Lenski’s estimate is based on all mutations, not the just the tails. However, my point remains: that you cannot extrapolate from the total numbers north and south of neutral to the numbers only a little bit north and south of neutral, and, in a skewed distribution, you must not.

    With regard to my point about a changing environment – from Gerrish and Lenski:

    A second assumption of our analyses is that neither the beneficial mutation rate nor the distribution of selection coefficients changes over time. But in a constant environment, a population becomes better adapted with time, leaving progressively less room for further improvement. It is likely that a welladapted population has (i) a lower overall rate of beneficial mutation, (ii) a smaller average effect of beneficial mutations, or both. Consequently,  = (w) may be a
    decreasing function of fitness, whereas = (w) may increase with fitness. These parameters are therefore constant only when w is constant. This condition may
    be met in an environment that changes just fast enough to counter adaptation of a population.

    http://myxo.css.msu.edu/lenski.....Lenski.pdf

  56. Hi Elizabeth. I really liked your post at 54. I think it’s well-reasoned and that you may well have some valid points.

    BA77:

    Mung, If it is truly a random mutation within a functional sequence, such as a typo in a sentence, then you are clearly moving away from optimal functionality to sub-optimal functionality and are thus ‘slightly detrimental’. If it is ‘sub-functional or non-functional’ energetic burden will increase and decrease fitness thus favoring removal by further mutation/selection.

    Well, BA, One of the things I cared for the least in Sanford’s book was his attempt to equate mutations with changes to English text, so I don’t find your use of the same problematical analogy compelling either.

    If a random mutation isn’t the same as a typo then what are you left with?

    With most typos, I can still figure out what the intent was, iow, I can tell it’s a typo.

    I’ve already dealt with the fallacy of the “energetic burden” argument.

  57. Well mung, once again we disagree.

  58. 58
    Elizabeth Liddle

    Thanks Mung.

    Made my day :)

  59. Elizabeth, just one little problem in your trying to maneuver the data to your desired conclusion of VSBMs, why in the world were only 5 beneficial (loss of function) mutations found by Lenski, after billions upon billions of mutations after 50,000 generations, to use in his most recent experiment???. If the plethora of VSBM were truly as great as you imagine them to be, with a simple change in environment, should not you have some ACTUAL evidence for your desired conclusion, instead of just high talk and shuffling of boundaries on paper???

  60. Basically Elizabeth, I just want to see some vertical evolution instead of talk so that you may even have a pretense of being scientific!!!

  61. 61
    Elizabeth Liddle

    What do you mean by “vertical evolution”, bornagain77?

    And at 59: the 5 “beneficial” mutations found by Lenski et al were not VSBMs – if they had been, they wouldn’t have been found!

    They were plain old BMs.

    And if, by “vertical” evolution, you mean population change in fitness down a single lineage, then Lenski’s E-coli are an example of “vertical” evolution. Brand new mutations (not pre-existing) resulted in increased fitness.

  62. Dang it Elizabeth, man I want to see some fireworks:

    Lenski DID NOT pass the fitness test against the parent strain in native environment!!!

    Is Antibiotic Resistance evidence for evolution? – ‘The Fitness Test’ – video
    http://www.metacafe.com/watch/3995248

    Thank Goodness the NCSE Is Wrong: Fitness Costs Are Important to Evolutionary Microbiology
    Excerpt: it (an antibiotic resistant bacterium) reproduces slower than it did before it was changed. This effect is widely recognized, and is called the fitness cost of antibiotic resistance. It is the existence of these costs and other examples of the limits of evolution that call into question the neo-Darwinian story of macroevolution.
    http://www.evolutionnews.org/2.....s_wro.html

    Michael Behe’s Quarterly Review of Biology Paper Critiques Richard Lenski’s E. Coli Evolution Experiments – December 2010
    Excerpt: After reviewing the results of Lenski’s research, Behe concludes that the observed adaptive mutations all entail either loss or modification–but not gain–of Functional Coding ElemenTs (FCTs)
    http://www.evolutionnews.org/2.....41221.html

    Lenski’s e-coli – Analysis of Genetic Entropy
    Excerpt: Mutants of E. coli obtained after 20,000 generations at 37°C were less “fit” than the wild-type strain when cultivated at either 20°C or 42°C. Other E. coli mutants obtained after 20,000 generations in medium where glucose was their sole catabolite tended to lose the ability to catabolize other carbohydrates. Such a reduction can be beneficially selected only as long as the organism remains in that constant environment. Ultimately, the genetic effect of these mutations is a loss of a function useful for one type of environment as a trade-off for adaptation to a different environment.
    http://www.answersingenesis.or.....n-bacteria

    Elizabeth, that is a big fat dud as far a evolutionary fireworks are concerned. Think about it Elizabeth, the programming in DNA is vastly superior to anything man has yet programmed!!!

    Systems biology: Untangling the protein web – July 2009
    Excerpt: Vidal thinks that technological improvements — especially in nanotechnology, to generate more data, and microscopy, to explore interaction inside cells, along with increased computer power — are required to push systems biology forward. “Combine all this and you can start to think that maybe some of the information flow can be captured,” he says. But when it comes to figuring out the best way to explore information flow in cells, Tyers jokes that it is like comparing different degrees of infinity. “The interesting point coming out of all these studies is how complex these systems are — the different feedback loops and how they cross-regulate each other and adapt to perturbations are only just becoming apparent,” he says. “The simple pathway models are a gross oversimplification of what is actually happening.”
    http://www.nature.com/nature/j.....0415a.html

    ,,, yet here you sit Elizabeth with 5 pitiful excuses for beneficial (loss of function) mutations after the equivalent of 2,000,000 years of human evolution!!!! This is not impressive Elizabeth to put it very mildly!!!!

  63. What do you mean by “vertical evolution”, bornagain77?

    That’s when you turn the petri dish on it’s side.

  64. Lizzie:

    In #54 you state, “Firstly , it is true that he assumes a cliff edge (See Figure 9).”

    In figure 3d (p. 32 of the paperback edition), he adds the beneficial mutations to Kimura’s distribution, although he can’t draw it to scale because the detrimental mutations outnumber the beneficial ones by between 10,000 and 1,000,000 to one. He doesn’t “assume” a “cliff edge”, he deduces it from the magnitude of that difference, which he gets straight from the literature.

    Regarding #55, your quote from Gerrish and Lenski contains the telling phrase, “It is likely”, which signals that they have left the arena of hard data and entered the realm of speculation–speculation, I submit, that is heavily influenced by an a priori commitment to a naturalistic, Darwinian explanation. Their belief on this point is undermined by the results from Lenski’s own experiments on bacteria plus the results of mutagenic experiments on fruit flies and plants, namely that all “beneficial” mutations in these experiments came as a result of genome degradation–loss of information and loss of biological function.

    So let’s take the data from the OP–each new generation of humans contains on average 60 new mutations. Now, we can assume that those that get passed on to future generations are “near neutral”, since those that can be “seen” by selection will be selected out. However, since the ratio of detrimental to beneficial mutations, even “near neutral” ones, is at least 10,000 to one, we can assume that all 60 are detrimental. So if a generation is 25 years, then in one million years, there will be 250,000 X 60 = 15 million near neutral BUT deleterious mutations being carried in the genomes of each human being.

    Now we don’t know enough yet about how the genome works to be able to calculate with certainty what the effect of such a load would be, so Sanford invokes an analogy: one “mutation” in, say, the Encyclopedia Britannica will degrade one word or duplicate a paragraph, but will have minimal effect on the work’s comprehensibility. However, there will certainly come a point where an accumulation of such errors will seriously impair its usefulness, and there will also come a point where it has become incomprehensible.

    Now I know that an analogy is not a proof, and you can continue to believe that this relentless accumulation of mutations will not have lethal consequences in the long run, but Lizzie, if you do, I will have to agree with Bornagain (although I don’t agree with his style) that you are in denial.

  65. 65
    Elizabeth Liddle

    Bruce, the word “likely” does not indicate that a finding is “speculation” rather than “data”. A likelihood estimate is often derived from data, and also often derived from theoretical models that may later be tested against data.

    The series of Figures 3a to 3d are entirely theoretical; the ones based on Kimura’s paper are based on Kimura’s theoretical model. Lenski’s “likehoood” is based on another theoretical model.

    But the biggest error is Sanford’s 3d which is neither Kimura’s nor Lenski’s but something he has cobbled together from both, and based, as I tried to explain, IMO, on a misunderstanding of both.

    As for “assuming” vs “deducing”: he does note “deduce” the cliff edge. He simply assumes that it must be there. For some bizarre reason he takes Kimura’s theoretical model for deleterious mutations only, shows the “VSDM” zone (i.e. those theoretically deleterous mutations that are “effectively” neutral, and then jams next to the zero line on the positive side, the population of observably beneficial mutations (BMs), totally ignoring the nearly neutral zone between zero and BMs(i.e. the VSBM zone).

    Obviously he assumes it doesn’t exist, but he gives absolutely no reason for this assumption, and it makes no sense. Why should mutations increase exponentially (Kumura’s assumption) in frequency as deleteriousness goes from Deleterious to Slightly Deleterious to Very Slightly Deleterious as they approache zero, and then jump straight to “Beneficial” without passing through Very Slightly Beneficial, to Slightly Beneficial on the way?

    It makes no sense at all, and there is neither data nor theory to support it. At least none that I know of and none that Sanford provides.

    As for the mutagenic experiments, they are irrelevant. Blasting fruitflies with radiation isn’t going to produce more “slightly beneficial” or “slightly deleterious” mutations – it’s going to produce grossly deleterious mutations.

    As for the “Loss of function” argument; it is of course true that sometimes a new function is gained at the expense of an old one, and if the new one is more beneficial than the old one in the current environment,then the new one will tend to propagate through the population.

    However, this is not always the case; sometimes the new function is an additional use for an old function (gene is expressed under a new set of conditions); sometimesthe new function is a use for a gene that has been inactive or irrelevant for a while; sometimes the new function replaces a function that is duplicated elsewhere (may even be a duplicate gene, but not always; most functions are polygeneic).

    Then there is the whole issue of epistasis, which Sanford ignores.

    And of course there is the absolutely crucial point that I made in my earlier post that the mode of the distribution itself will move depending on the environment!

    So far from being “in denial” (I do wish people wouldn’t assume that if someone disagrees with them, they are “in denial” :)) as I see it neither Sanford’s argument nor his evidence support his overall case at all.

    He has a couple of good points, the best of which that it is true that in a small effective population, genetic entropy becomes a problem. That is why inbreeding is problematic, and why species may start to become endangered even when there are many hundreds of individuals still in existence.

    It is also true that in a relatively benign environment, mutations that are harmless in that environment may build up, and prove deleterious if the environment suddenly becomes much harsher. That is probably an important factor in extinctions.

    So both those points are good. But Sanford draws inferences about “Genetic Entropy” that go well beyond those conditions, and these are simply not justified either by theory or data.

  66. 66

    Ok, Lizzie, I’m not going to argue with you any more. It is my opinion that you are unwilling to see the obvious, but clearly nothing I can say is going to convince you of that, and I’m sure you have a similar opinion of me, so I guess we’ll just have to agree to disagree.

    Cheers,
    Bruce

  67. 67
    Elizabeth Liddle

    Well, no, Bruce, I don’t have a “similar opinion of you”.

    I tend to assume that if something that seems obvious to me is not obvious to someone else, it’s either because they are in possession of some information that I don’t have, or I am in possession of some information they don’t have. Occasionally, I come to the conclusion that they really have some psychological block or something, but it’s rare.

    Which is why it puzzles me when people seem so readily to jump to that conclusion.

    I’ve read Sanford’s book in great detail; I’ve read the papers he cites. It’s my considered view that he has misunderstood those papers and, in addition, made a number of flawed arguments, even given what I consider are his flawed premises.

    You may well disagree, and of course I won’t continue to press the point with you if you don’t want to discuss it.

    But it does sadden me, I admit, when someone jumps to the conclusion that I am in “denial” rather than at least investigate the alternative, which is that I might have good reasons for my views (even if those reasons don’t turn out to be good enough).

    But, FWIW, I have not jumped to that conclusion wrt to you. Which is why I find it somewhat frustrating that rather than explain to me why you think my point about Kimura’s graph is wrong, and why you think that Lenski’s likelihood estimate is “speculation” (yet Kimura’s entirely theoretical model is apparently not), you simply assume I am in “denial” and leave it at that.

    :(

    Still, I guess it was nice to get this far :)

    Cheers

    Lizzie

  68. Elizabeth, perhaps actual evidence for your position would help???

  69. Ah, Lizzie, you have won me back, you have. I am so used to people in these blogs defending a position instead of really considering the points that have been made, that I find it quite refreshing that you don’t seem to be in that mold. I have been in your position (that is, responding to several adversaries with no allies) a number of times when the subject matter is theology rather than materialism and/or Darwinism, as I am a theist but not a Christian, and my views are substantially at odds with most if not all of the Christian theists who post and comment here. It is frustrating when one makes a very good point and it is simply not seen because people’s commitment to their world view is so strong that they cannot admit any possible valid challenge to it.

    I concluded that you were defending a position rather than genuinely seeking truth mainly on the basis of your characterization of Sanford’s construction of the distributions illustrated in 3a through 3d. It seems to me quite obvious why he has constructed them the way he has, particularly 3d, and my reading is that he has justified his conclusions quite thoroughly.

    What he has done in 3d, as I see it, is to take Kimura’s graph, which is essentially the distribution of negative mutations, both selectable and “near neutral”, and add the beneficial mutations to it. And he assumes the exact same shape of distribution. However, as he states quite clearly, since the ratio of detrimental to beneficial mutations is at least 10,000 to one, an assertion he backs up with several different references and arguments, the beneficial mutations will be invisible on the graph at the scale at which it is drawn. So he includes a tiny triangle on the right side to represent the distribution of beneficial mutations. So your statement in #65, “Obviously he assumes it doesn’t exist, but he gives absolutely no reason for this assumption, and it makes no sense,” seems completely unjustified to me.

    “As for the mutagenic experiments, they are irrelevant. Blasting fruitflies with radiation isn’t going to produce more ‘slightly beneficial’ or ‘slightly deleterious’ mutations – it’s going to produce grossly deleterious mutations.”

    How do you know this? It seems to me that increasing the rate of mutation with mutagenic agents should produce all manner of mutations–severe, near neutral, and everything in between. Do you have a reference that supports your claim?

    Regarding the idea that a shift in the environmental conditions can shift the graph, my understanding, based on Behe’s work and other sources I have read (including Sanford), all the actual experimental and observational evidence supports the conclusion that an increase in fitness in a species to adapt to an environmental stress is universally accomplished by breaking existing genes in some way, resulting in a net loss of biological function. This is true for Lenski’s bacteria, insects adapting to pesticides, bacteria adapting to antibiotics, humans adapting to Malaria (sickle cell anemia), and the malarial parasite adapting to anti-malarial drugs. So while it is true that in a stressful environment a detrimental mutation can increase fitness for that particular environment, the evidence suggests that it is virtually always by decreasing the amount of functional information in the genome, and thus in the long run contributing to genetic entropy. Note also that these examples do not support the contention that the entire graph has shifted to the left, but rather that certain few (very few) mutations have crossed over the line from detrimental to beneficial.

    So, Lizzie, I take back my accusation of your being in denial. However, I don’t see that you have really understood Sanford’s argument, as I have explained above.

    It’s refreshing discussing these topics with you, really.

    Bruce

  70. 70
    Elizabeth Liddle

    I’m touched, Bruce :)

    OK, point by point:

    I concluded that you were defending a position rather than genuinely seeking truth mainly on the basis of your characterization of Sanford’s construction of the distributions illustrated in 3a through 3d. It seems to me quite obvious why he has constructed them the way he has, particularly 3d, and my reading is that he has justified his conclusions quite thoroughly.

    What he has done in 3d, as I see it, is to take Kimura’s graph, which is essentially the distribution of negative mutations, both selectable and “near neutral”, and add the beneficial mutations to it. And he assumes the exact same shape of distribution. However, as he states quite clearly, since the ratio of detrimental to beneficial mutations is at least 10,000 to one, an assertion he backs up with several different references and arguments, the beneficial mutations will be invisible on the graph at the scale at which it is drawn. So he includes a tiny triangle on the right side to represent the distribution of beneficial mutations. So your statement in #65, “Obviously he assumes it doesn’t exist, but he gives absolutely no reason for this assumption, and it makes no sense,” seems completely unjustified to me.

    OK, well let me try to explain exactly what I meant.
    First of all, the Kimura paper from which Sanford takes the exponential plot is a completely theoretical paper (and none the worse for that) about drift in deleterious mutations including mutations that have selection coefficients at or near zero. It is not a data paper. It makes the math much easier to stop at zero, because that way you can model the distribution below zero as an monotonic function, which he does. Then, Sanford quotes Gerrish and Lenski, in another partly theoretical paper, but one that is tested on actual data. Their paper is not about deleterious mutations but about beneficial mutations, specifically, beneficial mutations in asexually reproducing populations, in which there is no cross-over. In such populations, beneficial mutations will tend to “compete”, and leading to a “law of diminishing returns” whereby the greater the beneficial mutation rate, the smaller the probability that a new beneficial mutation will go to fixation in the population. Interestingly, Gerrish and Lenski assume a monotonic (exponential, in fact) distribution for beneficial mutations for exactly the same reasons as Kimura assumes one for deleterious ones. In support of this, they cite Elena et al (1998) who explicitly studied the distribution of selection coefficients in E coli, and found a negatively skewed distribution of selection coefficients with a long negative tail (severely deleterious mutations) and a mode that was less than 1 (i.e. deleterious); however there is no “cliff edge” at one – there is monotonic, exponential-type decrease, albeit slightly steeper, but which is substantially non-zero at values above 1.

    So Sanford seems to have regarded Kimura’s theoretical exponential <1 plot as indicating that the frequencies above 1 (not even shown) are neglible, and then grafted on to it a number derived from Gerrish and Lenski, without apparently having read the the Gerrish and Lenski paper itself, and having ignored both the cited Elena datapaper, and, indeed, common sense!

    “As for the mutagenic experiments, they are irrelevant. Blasting fruitflies with radiation isn’t going to produce more ‘slightly beneficial’ or ‘slightly deleterious’ mutations – it’s going to produce grossly deleterious mutations.”

    How do you know this? It seems to me that increasing the rate of mutation with mutagenic agents should produce all manner of mutations–severe, near neutral, and everything in between. Do you have a reference that supports your claim?

    Not to hand, but I guess I could dig some out. But think about it logically: if you increase the rate of mutation dramatically above normal levels, you will certainly induce a much larger rate of severely deleterious mutations. And if your population now bears large numbers of severely deleterious mutations, the odd sweetener in the form of a slightly beneficial mutation isn’t going to do it much good. After all, to take an extreme case, if a mutation renders you infertile, another mutation that makes you slightly more attractive to a mate isn’t going to increase the number of offspring you leave! This is why epistasis is so important, is what the Gerrish and Lenski paper is all about, and which Sanford completely ignores, except when he tackles beneficial mutations (see below) and gets it wrong!.

    Regarding the idea that a shift in the environmental conditions can shift the graph, my understanding, based on Behe’s work and other sources I have read (including Sanford), all the actual experimental and observational evidence supports the conclusion that an increase in fitness in a species to adapt to an environmental stress is universally accomplished by breaking existing genes in some way, resulting in a net loss of biological function. This is true for Lenski’s bacteria, insects adapting to pesticides, bacteria adapting to antibiotics, humans adapting to Malaria (sickle cell anemia), and the malarial parasite adapting to anti-malarial drugs. So while it is true that in a stressful environment a detrimental mutation can increase fitness for that particular environment, the evidence suggests that it is virtually always by decreasing the amount of functional information in the genome, and thus in the long run contributing to genetic entropy. Note also that these examples do not support the contention that the entire graph has shifted to the left, but rather that certain few (very few) mutations have crossed over the line from detrimental to beneficial.

    Well, what I would say is that Sanford fails to recognise that “fitness” is always computed relative to the current environment. It makes no sense in population genetics terms to say that a mutation increases fitness but is “really” detrimental. If it increases fitness it increases fitness.

    It may be fair to say that it increases net fitness according to a law of diminishing returns (and this is what the Gerrish and Lenski paper was about) – a beneficial mutation may replace a mutation that did something else quite useful but was not quite as beneficial. But this isn’t always even the case. In one of the recent Lenski lab papers reviewed here, one mutation was not beneficial at all until another came along, and then it was (so epistasis can be positive as well as negative). And not all mutations involve the loss of something – a mutation can happen in a duplicate gene, or a duplicate function. Or it can simple usefully extend the range of conditions under which a gene is expressed. Or, in the case of sickle cell, a mutation can be helpful if heterozygotic but harmful if homozygotic. And this is simply the special case of what are probably numerous gene-gene interactions – it’s the cocktail you inherit that decrees your fitness, rather than any one gene. A gene may be beneficial in genotype, but deleterious in another. So not only is the selection coefficient a function of the current external environment, it’s a function of the genetic environment too. Epistasis is complicated!

    So, Lizzie, I take back my accusation of your being in denial. However, I don’t see that you have really understood Sanford’s argument, as I have explained above.

    It’s refreshing discussing these topics with you, really.

    Bruce

    And with you :) I had to rush the last part of my post, so I hope it makes sense. Feel free to probe if it doesn’t :)

  71. Elizabeth Liddle:

    I’ve read Sanford’s book in great detail…

    In that case, how can you say this?

    Then there is the whole issue of epistasis, which Sanford ignores.

    Why should mutations increase exponentially (Kumura’s assumption) in frequency as deleteriousness goes from Deleterious to Slightly Deleterious to Very Slightly Deleterious as they approach zero, and then jump straight to “Beneficial” without passing through Very Slightly Beneficial, to Slightly Beneficial on the way?

    When I look at the graph I see a curve.

    So it looks to me like Sanford is doing what you claim he does not do, which is show a change in the numbers through various stages of very slightly beneficial to beneficial.

    So I think you’re misrepresenting Sanford.

    There;s a line in the middle. Can we assume that’s neutral?

    There’s a curve on the left of he line, which is deleterious, and a curve on the right of the line, which is beneficial.

    Do you not see a curve on the right as well?

  72. 72
    Elizabeth Liddle

    Hi, Bruce!

    I assume you are looking at Figure 3d right?

    What he has done is to take Kimura’s theoretical monotonic (exponential, I think) curve on the left of zero, and then, to the right of zero, still within the “no selection zone” added a tiny (but, he says drawn “relatively large”) triangle representing the 1-in-a-million “beneficial mutations” estimated by Lenski. But these “1-in-a-million” BMs estimated by Lenski (with very important caveats – he is talking about an already adapted population) are those that are selected, they are not those in the “no selection zone. So Sanford’s tiny triangle needs to be moved along to the right outside the shaded zone. Then, if he joined the mode at zero to the triangle in its new position he’d have something a bit more sensible, but it would, unfortunately, undermine one of his points, i.e. that even the beneficials are unselectable. It’s the selectable beneficials that Lenski counted.

    But in any case, we have actual data from Elena et al, demonstrating that what I have described above is reflected in actual data.

    And the point about the “no selection” zone is that drift still occurs. If only VSDMs were in the “no selection zone” Sanford might conceivably have a point, but because he leaves out the VSBMs, which are also subject to drift, that point is somewhat cancelled.

    But the most important thing that Sanford ignores is that the selection coefficient of an allele is itself a function of the environment, and the environment is not only constantly changing (and if it changes, the number of BMs will go up, as I pointed out above), but the evolving population itself is part of that environment.

    And that is what the very interesting Gerrish and Lenski paper is about. Because they froze the ancestral population, they can identify whether any new mutation in one lineage is beneficial relative to the ancestral population. And what they find is quite a few beneficials. However, when these beneficials have to compete with other individuals bearing different beneficials, then they may be relatively neutral,or even deleterious!

    This isn’t epistasis of course, but what they term “clonal interference”.

    I have the Gerrish and Lenski paper(also the Elena paper), btw, so if you want to contact me (best way is by PM at Talk Rational – I’m “Febble”) I could send it to you.

    But do remember that Kimura’s exponential is a mathematical convenience, to give a monotonic function at values less than 0. A distribution across zero wouldn’t peak at infinity!

    Also, the mode is probably not at zero (probably below, for a well-adapted population).

  73. Elizabeth Liddle, as has been pointed out to you repeatedly, the Lenski ‘beneficial mutations’ are shown by Behe to in fact be ‘loss of function’ mutations that are detrimental on a molecular scale. i.e. They are only beneficial in the extremely narrow sense of ‘burning a bridge’,, Thus it is only by ‘craziness’ that you can possibly construe these as being positive evidence for neo-Darwinian evolution;

    Michael Behe’s Quarterly Review of Biology Paper Critiques Richard Lenski’s E. Coli Evolution Experiments – December 2010
    Excerpt: After reviewing the results of Lenski’s research, Behe concludes that the observed adaptive mutations all entail either loss or modification–but not gain–of Functional Coding ElemenTs (FCTs)

  74. 74
    Elizabeth Liddle

    But this is a quite different argument, ba77.

    It is not the argument that Sanford is making in his distribution plots.

    And is actually irrelevant to them, because “beneficial” in population genetics only means: increases net fitness in the current environment.

    It doesn’t refer to something that would result in net loss of fitness in some other environment. Yes, bridges are often burned (though not always). You evolve a wing, you lose your arms. The birds don’t seem to miss them :)

  75. No Elizabeth, it is just plain crazy to say ‘breaking stuff will lead to increased functional complexity’. I don’t care how you dress it up Elizabeth, to presuppose you can produce functional complexity, which far, far, surpasses anything man has ever done in his most advanced machines, by a process that consistently ‘breaks stuff’, is to mock logic, defy rationality, and commit yourself firmly to a field of completely unsubstantiated pseudo-science

  76. 76
    Elizabeth Liddle

    That’s fine, ba77: I disagree, but it’s a fair point.

    It’s just not relevant to Sanford’s Figure 3d which is what we were talking about.

    Selection coefficients (the X axis on the plot) are relative not absolute and they are relative to the current environment.

    If you want to discuss the issue as to whether a mutation can be beneficial without “breaking” an existing useful function, that’s a quite different issue.

    There are quite a few mechanisms (and I gave several earlier) by which this can occur. One is where genes are duplicated; one is where functions are duplicated; one is where the same function is expressed under additional conditions.

    There are many others.

  77. Elizabeth, I am looking at Fig. 3d.

    The x (horizontal) axis is labeled mutation effect.

    Sanford has plotted a curve of decreasing frequency (the y axis) as the mutation effect becomes more positive.

    Yet you claim that Sanford does not do that. You are mistaken.

    he takes Kimura’s theoretical model for deleterious mutations only, shows the “VSDM” zone (i.e. those theoretically deleterous mutations that are “effectively” neutral, and then jams next to the zero line on the positive side, the population of observably beneficial mutations (BMs), totally ignoring the nearly neutral zone between zero and BMs(i.e. the VSBM zone).

    I see a curve. Don’t you see a curve? The frequency decreases as the effect increases. That’s what I see.

    Every one of those graphs has the same label for the x axis (mutation effect).

    Not only does he show a curve, but the entire curve falls within the “no selection zone”!

    So you are doubly mistaken.

    The text for 3d even reads: “it becomes obvious that essentially all beneficial mutations will fall within Kimura’s ‘no-selection zone’.”

    If you are trusting your memory, let me suggest that you actually refer to the book instead.

  78. Elizabeth Liddle:

    Then there is the whole issue of epistasis, which Sanford ignores.

    According to the index:

    epistasis: 53, 55, 58, 76, 100, 110, 124, 172, 173, 216, 224. see also Synergistic Epistasis in the Glossary.

    Ignores? Seriously?

  79. 79
    Elizabeth Liddle

    Mung @ #77

    Elizabeth, I am looking at Fig. 3d.

    The x (horizontal) axis is labeled mutation effect.

    Sanford has plotted a curve of decreasing frequency (the y axis) as the mutation effect becomes more positive.

    Yet you claim that Sanford does not do that. You are mistaken.

    he takes Kimura’s theoretical model for deleterious mutations only, shows the “VSDM” zone (i.e. those theoretically deleterous mutations that are “effectively” neutral, and then jams next to the zero line on the positive side, the population of observably beneficial mutations (BMs), totally ignoring the nearly neutral zone between zero and BMs(i.e. the VSBM zone).

    I see a curve. Don’t you see a curve? The frequency decreases as the effect increases. That’s what I see.

    Every one of those graphs has the same label for the x axis (mutation effect).

    Not only does he show a curve, but the entire curve falls within the “no selection zone”!

    So you are doubly mistaken.

    The text for 3d even reads: “it becomes obvious that essentially all beneficial mutations will fall within Kimura’s ‘no-selection zone’.”

    If you are trusting your memory, let me suggest that you actually refer to the book instead.

    Mung, I have the book right by me, but perhaps I didn’t make myself clear. Let me try again:

    Figure 3a shows a normal distribution with a mode at zero on the x axis. The x axis is labeled “mutation effect”. The caption makes it clear that this is meant to represent positive fitness greater than zero and negative fitness below zero. Sanford does not say relative to what, so we must assume that it is relative to some ancestral population (as opposed to a competing population).

    He calls this the “naive view”, as indeed it is.

    He then present Figure 3b, in which he simply removes the entire distribution that is greater than zero, leaving a “cliff edge” as you go cross the zero line. He says this represents the additional information that “essentially all mutations are deleterious”. He does not reference this assertion. However, we can agree that in a well adapted population, the vast majority of mutations will be either neutral or deleterious.

    But he says this distribution is “still too optimistic” and then presents Figure 3c.

    In this figure he has, firstly, replaced his half-bell curve with an exponential (or similar) function, and says it is “adapted from a figure by Kimura (1979)”.

    However, the “adaptation” consists of extrapolating Kimura’s graph beyond zero and assuming that the frequency beyond this point is in fact zero – that the frequency of mutations rises astronomically as we approach zero from below, then plummets to zero. He offers no justification for this extrapolation, and does not even mention the fact that Kimura’s graph does not even attempt to model the distribution values greater than zero. Kimura’s graph is a mathematical convenience, it does not represent data.

    He also shades in a zone either side of zero which he calls a “no selection zone”. In this he follows Kimura, except that of course Kimura does not model the distribution above zero.

    He finally presents Figure 3d, in which he adds a tiny triangle, within the “no-selection zone” at the base of his otherwise vertical cliff face at zero. He says that even his tiny triangle is enlarged so that it will show up on the drawing. So again, he is presenting a cliff face at zero, with a tiny pile of rubble at the base, not extending outside the “no selection zone”.

    He derives the size of this triangle from, among other sources, Gerrish and Lenski (1998).

    He then concludes that this is a realistic distribution and reveals that even the tiny percentage of “beneficial mutations” that exist are in the “no selection zone”.

    He has arrived at this conclusion in my view by a) piling error on error and b) ignoring actual data.

    His first two plots I will ignore as one is indeed “naive” and the second just silly. His third is, as I’ve said, a completely unsupported extrapolation from a theoretical paper by Kimura that dealt only with deleterious mutations, and was therefore able to utilise a monotonic function.

    And his fourth compounds the error made in his third by a misreading of Gerrish and Lenski.

    In fact, a data paper that he cites three times shows that his Figure 3d is wrong, in several ways, as indeed it must be.

    The Elena et al (1998) actually gives a distribution of mutations that shows that of course there is no spike at zero followed by a cliff edge, but a mode at rather less than zero, the curve starting its descent before zero is reached, descending more or less smoothly, and, in Elena’s sample, terminating before exiting the “no selection zone”. So he’d have been better off in some ways simply going with Elena’s distribution, which at least makes some sense.

    But his real error is in misinterpreting Gerrish and Lenski (1998) who, far from computing a “small triangle” within the “no selection” zone, give their figure (albeit a small one, and remember this is an asexually reproducing population) for beneficial mutations that are actually selected (and go to fixation).

    In other words, taking Elena et al and Gerrish & Lenski together, we must conclude that in asexually reproducing populations of E Coli, most mutations are deleterious compared with the ancestral population, some very deleterious, and those that are beneficial compared with the ancestral population, only a minor proportion go to fixation (i.e. are outside the “no selection zone”).

    In other words, the true distribution at least for E coli, is a distribution with a mode at less than zero, a long negative tail, a substantial shoulder either side of the mode that extends into the positive section of the x axis, and includes a tail that extends outside the “no selection zone”.

    And if we read Gerrish and Lenski more closely, we note that this distribution makes very specific assumptions about the environment itself.

    Sanford seems to ignore the fact that “fitness” as measured the sources he cites in support of his case, is a function of the current environment. And so, in any well-adapted population, the mode will tend to be below zero. Indeed, most lineages derived from Lenski’s ancestral colony were a lot fitter than that ancestral colony. In other words, they adapted. But once a population is optimised for an environment, there is very little room for any further improvement, especially in an asexually reproducing species. But change the environment, and the distribution will change as well, obviously.

    As for epistasis: yes of course, it is in Sanford’s index, but turn to his page 110. He regards it as “a sophisticated expression [that] signifies nothing”.

    In other words he ignores it as a factor (except to say that “even if it were valid, it makes the genetic situation worse not better”).

    And to cap it all, he cites Elena and Lenski (1997) in support of the claim that the “concept is not valid”. Elena and Lenski do no such thing. The paper itself is a letter to Nature about specific theory regarding the evolutionary origins of sexual reproduction. They dismiss the theory, not because the “concept [of synergistic epistasis] is not valid” but because both synergistic and antagonistic epistasis occurs in asexual populations:

    Because we performed tests for interactions, and not all were independent (using the same nine mutations), we then applied the Bonferroni method to adjust significance levels for the multiplicity of tests. Even with this conservative approach, three synergistic and four antagonistic interactions are significant. Therefore, the mutational deterministic hypothesis seems to fail not because interactions between deleterious mutations are very rare, but rather because synergistic and antagonistic interactions are both common.

  80. Sanford:

    Epistasis – The different mutations that affect the same trait often interact, and when this happens, it is called epistasis. A deleterious mutation may be much more or less deleterious depending on the absence or presence of other mutations. Such epistasis creates non-heritable noise and strongly interferes with selection. Geneticists acknowledge that epistasis is important, but assume that positive and negative interactions largely cancel out.

    Elizabeth:

    Then there is the whole issue of epistasis, which Sanford ignores.

    So when you said that Sanford ignores the whole issue of epistasis you didn’t mean to imply that he is ignorant of epistasis?

    Sanford:

    Synergistic epistasis – The term synergistic epistasis is normally only used in attempting to rationalize how genomes might be prevented from degenerating continuously. The basic concept is that epistasis (interaction) between mutations is consistently negative. Therefore, as mutations accumulate, each new mutation has a greater and greater average fitness deleterious effect. This is the exact opposite of the standard multiplicative population genetics model, wherein each mutation has less and less effect (one or both models must be wrong). The synergistic epistasis model is extremely artificial and biologically un-realistic. Even if the model is granted, it can be shown that this mechanism fails to stop degeneration when linkage and the interaction between mutations and non-mutations are also taken into account.

    Elizabeth:

    Then there is the whole issue of epistasis, which Sanford ignores.

    And when you said that Sanford ignores the whole issue of epistasis you didn’t mean to imply that he failed to mentioned it multiple times?

    Sanford:

    This problem of the fundamental inter-relationship of nucleotides is called epistasis. True epstasis is essentially infinitely complex, and virtually impossible to analyze, which is why geneticists have always conveniently ignored it.

    Elizabeth:

    Then there is the whole issue of epistasis, which Sanford ignores.

    Funny, Sanford accuses your side of ignoring it.

    Sanford:

    synergistic epistasis .. means that mutations interact such that several mutations cause more damage collectively than would be predicted by their individual effects. At least one paper provides experimental evidence that the concept is not valid (Elena and Lenski, 1997). But even if it were valid, it makes the genetic situation worse, not better. We have always known that genic units interact, and we know that such epistasis is a huge impediment to effective selection. This fact is ignored by most geneticists because selection scenarios become hopelessly complex and unworkable unless such interactions are conveniently set aside. But now, when genetic interactions can be usedto cloud the problem of error catastrophe, the concept is conveniently brought forth and used in an extremely diffuse and vague manner, like a smoke screen

    Elizabeth:

    Then there is the whole issue of epistasis, which Sanford ignores.

    Only if by ignore you mean addresses it head on.

  81. 81
    Elizabeth Liddle

    OK, he discounts it, then.

    Golly, Mung, it’s like talking to a lawyer. Are you a lawyer?

    Still fair enough. Bad word choice on my part.

    Now, about those distributions….

  82. Now, about those distributions….

    Now, about those word choices…

  83. 83
    Elizabeth Liddle

    Obviously they were poor, as I have said.

    So are you going to tackle my posts regarding the distribution of mutations along the selection coefficient axis?

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