Behe on LYST

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A second highly selected gene, LYST, is associated with pigmentation, and changes in it are probably responsible for the blanching of the ancestors’ brown fur. Computer analysis for the multiple mutations of the gene showed that they too were almost certainly damaging to its function.

In fact, of all the mutations in the seventeen genes that were most highly selected, about half were predicted to damage the function of the respective coded proteins. Furthermore, since most altered genes bore several mutations, only three to six (depending on the method of estimation) out of seventeen genes were free of degrading changes [fn 2]. Put differently, 65 to 83 percent of helpful, positively selected genes are estimated to have suffered at least one damaging mutation.

  • Darwin Devolves p. 21

fn 2 is Table S7 of Liu et al.

Can we work through this one item at a time to see what people agree with or disagree with?

228 thoughts on “Behe on LYST”

  2. A second highly selected gene, LYST, is associated with pigmentation, and changes in it are probably responsible for the blanching of the ancestors’ brown fur.

    Agree or disagree? Anything controversial here?

  3. Mung: A

    Mung,
    There is no YES or NO answer unless one understands exactly what effect the mutations had on melanocytes… I was planning to do an in depth OP on this theme this Thursday…

  4. How about this?

    In fact, of all the mutations in the seventeen genes that were most highly selected, about half were predicted to be beneficial to the function of the respective coded proteins. Furthermore, since most altered genes bore several mutations, only three to six (depending on the method of estimation) out of seventeen genes were free of beneficial changes [fn 2]. Put differently, 65 to 83 percent of helpful, positively selected genes are estimated to have suffered at least one beneficial mutation.

    😎

  5. Behe would claim that the changing the terrestrial mammalian forelimb into the cetacean front fin is damaging because the cetacean is no longer able to walk on land. Behe assumes that any change from the initial function is damaging.

  6. T_aquaticus: Behe would claim that the changing the terrestrial mammalian forelimb into the cetacean front fin is damaging because the cetacean is no longer able to walk on land. Behe assumes that any change from the initial function is damaging.

    Then we are all devolved bacteria.

    Three cheers for devolution.

  7. T_aquaticus: Behe would claim that the changing the terrestrial mammalian forelimb into the cetacean front fin is damaging because the cetacean is no longer able to walk on land

    That remark has come up before, but I am not convinced he would argue that. As I understand Behe’s argument, it only applies to function of molecular features (genes, promotors, enhancers, etc), not to morphological, ecological or behavioural characters. So the cetacean fin only counts as an example of devolution if the function of most genes involved was broken or diminished in order to make the transition.

    Here is the scientific paper that introduced the “first rule of adaptive evolution”:

    Adaptive evolution can cause a species to gain, lose, or modify a function; therefore, it is of basic interest to determine whether any of these modes dominates the evolutionary process under particular circumstances. Because mutation occurs at the molecular level, it is necessary to examine the molecular changes produced by the underlying mutation in order to assess whether a given adaptation is best considered as a gain, loss, or modification of function. Although that was once impossible, the advance of molecular biology in the past half century has made it feasible. In this paper, I review molecular changes underlying some adaptations, with a particular emphasis on evolutionary experiments with microbes conducted over the past four decades. I show that by far the most common adaptive changes seen in those examples are due to the loss or modification of a pre-existing molecular function, and I discuss the possible reasons for the prominence of such mutations.

  8. Computer analysis for the multiple mutations of the gene showed that they too were almost certainly damaging to its function.

    Okay, how about his second statement. This is specifically about LYST. Anything controversial about it?

  9. What is it LYST does? I don’t recall. It’s “associated with pigmentation”, but in what way?

  10. Corneel: That remark has come up before, but I am not convinced he would argue that. As I understand Behe’s argument, it only applies to function of molecular features (genes, promotors, enhancers, etc), not to morphological, ecological or behavioural characters. So the cetacean fin only counts as an example of devolution if the function of most genes involved was broken or diminished in order to make the transition.

    Here is the scientific paper that introduced the “first rule of adaptive evolution”:

    Ahh yes I remember that one. I should be interesting to use Behe’s definitions in that paper and analyze the polar bear mutations. But we’re going to need more details about the individual genes and mutations. Someone has the link for the polar bear paper Behe got the list from, at hand, and can link it here for convenience?

  13. Oh man oh man, Behe is really stacking the deck in his favor here. From his original paper. Here is where he defines the categories:

    1) A “loss-of-FCT” adaptive mutation is a mutation that leads to the effective loss of the function of a specific, pre-existing, coded element, while adapting an organism to its environment. The loss of the ability of a frame-shifted gene to produce a functional product, of an altered promoter to bind a transcription factor, or of a mutated protein to bind its former ligand, are examples of loss-of-FCT mutations.

    2) A “gain-of-FCT” adaptive mutation is a mutation that produces a specific, new, functional coded element while adapting an organism to its environment. The construction by mutation of a new promoter, intron/exon splice site, or protein processing site are gain-of-FCT mutations. Also included in this category is the divergence by mutation of the activity of a previously duplicated coded element.

    3) A “modification-of-function” adaptive mutation is a mutation whose defining property is negative—while adapting an organism to an environment, it does not lead to the loss or gain of a specific FCT. This definition is intended to be broad enough to act as a “catch-all” for anything that falls outside the first two modes. It includes point mutations as well as other mutations that have a quantitative effect on a preexisting FCT, increasing or decreasing its strength, for instance, or shifting its activity somewhat (such as allowing a protein to bind a structurally-related ligand at the same site as its normal substrate), but without effectively eliminating it. The category “modification-of-function” also includes the simple duplication of features, without divergence of activity, such as a gene or regulatory region, since this process does not by itself produce a new functional element, although it may, like other events classified here as “modification-offunction,” be a step to future gain-of-FCT events. It also includes mutations that may act by more amorphous means, such as rearranging gene order, or changing the distance or orientation between two interacting elements (e.g., the deletion of a stretch of DNA that brings two interacting transcription factors closer, or that affects their orientation with respect to each other). This category is dubbed “modification-of-function” rather than “modification-of-FCT ” in order to emphasize that the mutation may not necessarily exert its influence through alteration of a discrete coded element, as in the above amorphous examples.
    In order to fall under any of the above three categories, a mutation must be adaptive. Therefore, if, for instance, a mutation causes a transcription factor binding site to be formed or lost, but the mutation is either neutral or deleterious, it is excluded from consideration. Although assignment of an adaptive mutation to one of the modes above may occasionally be ambiguous, the assignment is straightforward in the great majority of cases in which molecular changes are elucidated, as we shall see below.

    Notice the last part I have highlighted in bold. Behe has heavily stacked the deck in favor of his thesis here by insisting that for a mutation to count as “gain of FCT” it must be also adaptive, not just neutral. That means that constructive neutral evolution (CNE), for example, which is hypothesized to be one of the ways the eukaryotic spliceosomal complex grew to it’s extreme size, would essentially mostly be considered irrelevant to Behe and fall outside his categories. But those are some of the very processes by which biologists think much of the molecular complexity we see actually evolved, and here Behe is defining it to be irrelevant.

  15. Mung: Computer analysis for the multiple mutations of the gene showed that they too were almost certainly damaging to its function.

    Having now read the relevant parts of the paper I agree on the LYST example, the conjunction of mutations that affect it’s function are likely to constitute what Behe defines as a “loss-of-FCT” in his 2010 paper.

    Technically it is possible that it is actually a “modification-of-FCT”, if the original function of the LYST gene has not dropped to a level of zero. In so far as any degree of it’s original function is retained, such as regulating transport of melanin in/out of melanosomes, however small it would actually constitute an example of “modification-of-FCT”.

    But being charitable to Behe, the function of LYST does seem to be degraded to such an extent that, even if it has so far only reduced in function, it’s eventual complete deactivation would seem to be “in the cards” so to speak, as the whiter polar bears become, the better camouflaged they would be in the arctic.

    Don’t tell phoodoo though, this is all impossible gibberish to him. Natural selection is an impossible tautology nobody can make sense of etc. etc.

  16. Rumraket: Behe has heavily stacked the deck in favor of his thesis here by insisting that for a mutation to count as “gain of FCT” it must be also adaptive, not just neutral. That means that constructive neutral evolution (CNE), for example, which is hypothesized to be one of the ways the eukaryotic spliceosomal complex grew to it’s extreme size, would essentially mostly be considered irrelevant to Behe and fall outside his categories. But those are some of the very processes by which biologists think much of the molecular complexity we see actually evolved, and here Behe is defining it to be irrelevant.

    I guess that makes Behe a Darwinist. Lulz

  17. Can we work through this one item at a time to see what people agree with or disagree with?

    It’s not a matter of agreement Mung, it’s a matter of Behe’s misrepresentation of the data.

    In the article’s link, click on “full text,” then click twice in “supplementary information” (I had to click it twice to get to the supplementary information, maybe it took a while to load) you’ll get a link to an excel file. Open that file, and then click on the tab corresponding to table S7. Check the mutations for LYST, check again what Behe claimed about those mutations. If that doesn’t strike you as deceptive then you have a serious problem.

    (I wasn’t able to upload the pdf I made from the exel file, sorry, you have to check the file yourselves.)

    ETA: The extended experimental procedures explain those columns, and the link is also under supplementary information, right below the link to the excel file.

    ETA: I linked to the files in this comment, but I explained how to get there yourselves in case you don’t trust my links.

  18. Rumraket: Having now read the relevant parts of the paper I agree on the LYST example, the conjunction of mutations that affect it’s function are likely to constitute what Behe defines as a “loss-of-FCT” in his 2010 paper.

    No, no, no, no, no and fuck no. Behe claims that he took the data from table S7 in that polar bear article. He said so in the book, he said so in his blog entry. He fucking misrepresented the fucking data.

    Fuck. What’s wrong with you all? I’m out of this fucked up discussion.

    For the record (first description corresponds to one method, second to another method for predicting if the mutations are benign or damaging):

    LYST 1046 D Y possibly damaging 0.947 benign 0.272

    LYST 1084 A S benign 0.045 benign 0.015

    LYST 1140 F L benign 0 benign 0

    LYST 1770 L F benign 0.005 benign 0.007

    LYST 2672 N K benign 0.032 benign 0.021

    LYST 2978 R S probably damaging 0.957 benign 0.445

    LYST 3784 Q H probably damaging 0.998 probably damaging 0.983

  19. Entropy: No, no, no, no, no and fuck no. Behe claims that he took the data from table S7 in that polar bear article. He said so in the book, he said so in his blog entry. He fucking misrepresented the fucking data.

    Yes he did, he misrepresented the BIG PICTURE. That doesn’t mean he misrepresented every single concrete example.

    There ARE examples of mutations that would constitute “loss of FCT” by Behe’s definition. That is not really in question.

    But Behe’s thesis is that these are the vast majority, and that they will always vastly outnumber so-called “gaint of FCT” mutations.

    Fuck. What’s wrong with you all?

    I don’t see what is wrong with agreeing that some particular instance of mutations would qualify as what Behe would define as a “loss-of-FCT”.

  20. Entropy: For the record (first description corresponds to one method, second to another method for predicting if the mutations are benign or damaging):

    LYST 1046 D Y possibly damaging 0.947 benign 0.272

    LYST 1084 A S benign 0.045 benign 0.015

    LYST 1140 F L benign 0 benign 0

    LYST 1770 L F benign 0.005 benign 0.007

    LYST 2672 N K benign 0.032 benign 0.021

    LYST 2978 R S probably damaging 0.957 benign 0.445

    LYST 3784 Q H probably damaging 0.998 probably damaging 0.983

    Yes, and the relative frequencies of “damaging” versus “benign” are important to analyze whether Behe is able to carry his thesis.

    And it is also important to analyze in better detail in what way these different proteins function, and to establish what the actual effect these mutations have on protein function. We already know the software predicts all function-affecting mutations as “damaging”, so since we can’t go by the software prediction alone, we have to try to understand what the proteins in question do.

    LYST, the Lysosomal Trafficking Regulator protein is a vesicular transport protein. This protein apparently functions by controlling the transport of the melanin pigment in and out of melanosomes. Apparently, mutations in this gene prevents the transport of melanin pigment (whether in or out), such that either none, or very little melanin, is deposited in the fur hair of polar bears.

    Now, in fact the distinction between none and little is important with respect to Behe’s main point, because Behe’s thesis is that most adaptive mutations are actually of the “loss-of-FCT” type. That means in so far as ANY melanin pigment is still transported in/out of lysosomes by the LYST protein, it will NOT qualify according to Behe’s own definition of “loss-of-FCT” and will instead qualify as a “modification-of-FCT”.

    As Behe writes in his 2010 paper: “3) A “modification-of-function” adaptive mutation is a mutation whose defining property is negative—while adapting an organism to an environment, it does not lead to the loss or gain of a specific FCT. This definition is intended to be broad enough to act as a “catch-all” for anything that falls outside the first two modes. It includes point mutations as well as other mutations that have a quantitative effect on a preexisting FCT, increasing or decreasing its strength, for instance, or shifting its activity somewhat (such as allowing a protein to bind a structurally-related ligand at the same site as its normal substrate), but without effectively eliminating it.“

    But it is entirely possible, and not at all implausible to me, that the LYST function has entirely ceased, and so the conjunction of fitness-affecting (adaptive) mutations that affect LYST has made it stop functioning. Another aspect of this analysis is to understand the fitness effects (if any) of the “benign” mutations. They might be benign to protein function, but if they’re selectively neutral (for example by being synonymous or silent), Behe can simply ignore them because then they don’t “qualify” for consideration under his absurdly deck-stacking definitions. In that way, Behe can simply say that they don’t affect his argument, because he only counts the relative frequencies of ADAPTIVE mutations, not the relative frequencies of ALL mutations.

    But that then becomes a very important point, because then we are forced to argue about whether Behe’s definitions of “loss”, “gain” or “modification” are sensible, instead of arguing about what the mutations even do. You see the problem here right? Behe’s insistence that only mutations with an ADAPTIVE value be considered under his scenario means Behe can simply ignore most synonymous mutations, or even mutations that change amino acids into very chemically similar ones on less consequential surfaces of proteins not involved in direct binding interfaces or substrate guiding tunnels, and so on. The more I think about his definitions, the more deceptively he has stacked the rules in his favor.

  21. It is now clear to me that this whole thing will probably come to revolve around debating the sensibility of Behe’s highly self-serving definitions of his categories. By explicitly not considering neutral mutations under his three categories, he can basically ignore the vast majority of molecular evolution as not being relevant to his categories.

    While we might sensibly consider a neutral mutation that affects the function of a protein a “modification” of function, Behe would not even consider such a mutation, and as such it’s relative frequency compared to Behe’s claim that most of them are “loss”-type mutations can be simply dismissed.

    That is extremely deceptive categorization. Good luck explaining this to his braindead sycophants who will spend exactly zero seconds of their life having a single critical thought about whether his defined categories make sense. They can and simply will point to them and say, “see, according to how Behe defines his categories, he’s right”.

  23. Mung: Computer analysis for the multiple mutations of the gene showed that they too were almost certainly damaging to its function.

    Okay, how about his second statement. This is specifically about LYST. Anything controversial about it?

    Oh boy. I was going to answer this as follows:
    “Nothing controversial. This statement is false.”
    but Rumraket wants to view Behe’s latest book in light of Behe’s 2010 paper.
    I view this as an unnecessary distraction. AIUI (and Mung, correct me if I am wrong) the computer analysis that Behe refers to is Liu et al.

    So his comment re LYST is wrong, plain and simple.

    [Personally, I still reckon that LYST has suffered degradation of function, but Behe has been making unsupported statements left right and center.]

  24. DNA_Jock: Rumraket wants to view Behe’s latest book in light of Behe’s 2010 paper.
    I view this as an unnecessary distraction.

    Well it does bring into question whether Behe is being consistent with his own definitions. Without knowing, if Behe is to make any sense at all in a way that is amenable to rational analysis, he must somewhere in his new book define his categories, and then in light of these categories try to “score” mutations he finds in the literature.

    My guess would be that Behe seems to think that the software output is roughly similar to his own categorization. But it is entirely possible that many of the mutations that are called “damaging” by the software, would qualify as “modification of function” according to his 2010 paper.

    The question then is whether he has modified (or even bothered to define) his categories in his new book.

  25. Rumraket: Yes, and the relative frequencies of “damaging” versus “benign” are important to analyze whether Behe is able to carry his thesis.

    Nope. He unambiguously claimed that he took the damaging part from the fucking table. He didn’t say that he reinterpreted the data by his own standards. Seriously Rum. You’re just giving the creationists excuses, and this is just nauseating. Our creationists were confronted with this obvious misrepresentation of the data, and you gave them a way out. I know they’d find an excuse themselves. That their standards suck when it comes to their preferred conclusions, but you helping them is just fucked up, given the situation.

  26. DNA_Jock: So his comment re LYST is wrong, plain and simple.

    Not wrong. A distortion of the data. The most obvious among the many distortions he made.

    Shit, I’m better off this discussion. I cannot stand the stench.

  28. phoodoo: But he is more qualified to speak on matters of biology than you right?

    On some biological subjects, sure. Others, probably not. Not that this is supposed to be the ultimate arbiter of the strength of one’s arguments. A person’s credentials might give some indication of how likely it is that they are sufficiently informed to hold an opinion on a subject, but it is only an indication. I would agree every argument needs to be analyzed on it’s own terms, not by who makes it or what title they have.

  29. Entropy: Nope. He unambiguously claimed that he took the damaging part from the fucking table. He didn’t say that he reinterpreted the data by his own standards.

    Well the good news is that Behe apparently has elected for a dictionary definition of “break/blunt” in the article he posted on EN&V in response to Jerry Coyne:

    The point was hardly obscure. Here’s the very epigraph of my book, right up front: “The First Rule of Adaptive Evolution: Break or blunt any gene whose loss would increase the number of offspring.” Notice again that “break” and “blunt” have distinct meanings. The relevant definition of blunt is: To make less effective; weaken. Is that really so hard to understand?

    That nullifies any attempt our resident IDiots could make for invoking Behe’s 2010 definitions (or other definitions in his book) to prove he is right. Behe has gone for a dictionary definition, and then interpreted the software output in light of a dictionary definition.

  30. dazz: The infamous table S7 doesn’t seem to be there

    LoL!

    Due to a lack of appropriate functional studies of polar bears,we were unable to directly identify causal variants. Nevertheless, we assessed the impact of polar bear-specific substitutions on human proteins for top-20 genes under positive selection by computational predictions: a large proportion (ca.50%) of mutations were predicted to be functionally damaging(Figures 4C and 4D,Table S7).

    Supplemental Information includes Extended Experimental Procedures, four figures, and seven tables and can be found with this article online at http://dx.doi.org/10.1016/j.cell.2014.03.054.

  32. Rumraket: Notice the last part I have highlighted in bold. Behe has heavily stacked the deck in favor of his thesis here by insisting that for a mutation to count as “gain of FCT” it must be also adaptive, not just neutral. That means that constructive neutral evolution (CNE), for example, which is hypothesized to be one of the ways the eukaryotic spliceosomal complex grew to it’s extreme size, would essentially mostly be considered irrelevant to Behe and fall outside his categories.

    That is exactly right Rumraket. That is why we hammer him for arguing against “Darwinism” which he defines as “positive selection dominated change.” This ignores, by definition, neutral evolution. He has constructed a straw man version of evolution to argue against. At some point, he has to engage with modern evolutionary science.

    You can read about Constructive Neutral Evolution here: https://discourse.peacefulscience.org/t/constructive-neutral-evolution/4675

    Turns out that IC systems easily evolve by neutral evolution.

  33. I was never the same since I lost my cell wall and the energetic outer membrane. I hired some mitochondria, and now I’m stuck with ’em. Oh sure, it’s loads better, but I still lost function. Bloody devolution 🙁

  34. Mung:
    See, according to how Behe defines his categories, he’s right.

    Q.E.D.

    In other words ,you believe me or your lying eyes?

  35. Mung:
    See, according to how Behe defines his categories, he’s right.

    Q.E.D.

    And the entire biosphere can evolve through mechanisms Behe considers either devolutionary, or irrelevant. He has not accomplished showing a problem with evolution.

    All the molecular complexity, and phenotypic diversity, and functionality of life could have evolved by a combination of mostly molecular “loss”, “modification of function”, a few “gains”, and lots of “irrelevant” mutation, and Behe has nothing to say about it.

  36. newton: In other words ,you believe me or your lying eyes?

    It’s worse. Behe could watch all the molecular and phenotypic complexity of eukaryotes evolve, and he’d call it “mostly loss/modifcation”, “mostly irrelevant”, and then concede a few occasional “gains”.

    He hasn’t defined what can or can’t happen, he’s defined what he will categorize it. The whole thing amounts to an argument about labels.

    It’s amazing.

  37. Rumraket: Behe could watch all the molecular and phenotypic complexity of eukaryotes evolve, and he’d call it “mostly loss/modifcation”, “mostly irrelevant”, and then concede a few occasional “gains”.

    I haven’t read the book yet but I think this is progress. Behe is not anti-evolution as I understand it. He just wants to quantify what evolution (ie RM/NS) can and can’t do and set boundries. That has been the point of his previous works any way and this seems to be more of the same. Narrowing the playing field a little at a time.

    We have some folks who think evolution is capable of doing almost anything and others who think it can’t do anything at all that is worthwhile. I would think folks would welcome efforts to clarify just what it is and is not capable of. Narrowing the focus of our inquiry is always helpful even if it’s just slightly.

    That is my 2 cents anyway

    peace

  38. DNA_Jock: So his comment re LYST is wrong, plain and simple.

    Since the majority of adaptive mutations in LYST appear to be actually “benign”, yes.

    Mung: Computer analysis for the multiple mutations of the gene showed that they too were almost certainly damaging to its function.

    Okay, how about his second statement. This is specifically about LYST. Anything controversial about it?

    Yes, it’s wrong and misleading. Behe ignores the “benign” mutations, and only shows the ones predicted to be “damaging”. So for the LYST example the frequency of “damaging” mutations isn’t high enough for them to substantiate his rule.

  39. A huge part of the problem is that when non-experts hear evolution they almost always think Darwinism and when experts say evolution they almost never mean Darwinism.

    Darwinism with it’s emphasis on the random nature of change is what the people I hang with really object to.

    I think folks like Swamidass should be hammering the “Darwin is dead” meme. If they did it would do a lot to assuage the hostility to “evolution” in lay Evangelicals and perhaps bring a little peace to science 😉

    peace

  40. I think the real question to be answered is: Where do novel structures come from? And as far as I can see Behe is asking how do we get the novel FCTs (Functional Coded ElemenTs) which are ultimately required to develop a complex higher animal from its purportedly simpler ancient ancestor?

    In a response to Behe Richard Lenski writes:

    We suggest that the shift to a diet consisting predominantly of fatty acids in polar bears induced adaptive changes in APOB, which enabled the species to cope with high fatty acid intake by contributing to the effective clearance of cholesterol from the blood.” In a news piece about this research, one of the paper’s authors, Rasmus Nielsen, said: “The APOB variant in polar bears must be to do with the transport and storage of cholesterol … Perhaps it makes the process more efficient.” In other words, these mutations may not have damaged the protein at all, but quite possibly improved one of its activities, namely the clearance of cholesterol from the blood of a species that subsists on an extremely high-fat diet.

    It appears Behe either overlooked or ignored the authors’ interpretation. Determining whether those authors or Behe are right would require in-depth studies of the biochemical properties of the protein variants, their activities in the polar bear circulatory stream, and their consequences for survival and reproductive success on the bear’s natural diet. That’s a tall order, and we’re unlikely to see such studies because of the technical and logistical challenges. The point is that many proteins, including ApoB, are complex entities that have multiple biochemical activities (ApoB binds multiple lipids), the level and importance of which may depend on both intrinsic (different tissues) and environmental (dietary) contexts. In this example, Behe seems to have been too eager and even determined to describe mutations as damaging a gene, even when the evidence suggests an alternative explanation.

    Lenski says that the polar bear version of APOB may be more efficient in clearing cholesterol and this would be an improvement in function. But cholesterol is a substance which animals need and so it’s not a matter of efficient clearance that is important, it is a matter of maintaining the correct balance of cholesterol in the system. This efficient clearing would be detrimental to animals with a diet which is less fatty than that of polar bears. Each animal maintains the balance which is suitable to its needs. Changes to APOB allow for these suitable modifications of its function, they don’t add any new function.

    Here they ask*, How do new adaptive FCTs arise?

    Behe argues that we do not generally observe the evolution of new adaptive FCTs* in the laboratory. Rather, when we observe adaptive evolutionary changes in the laboratory, they typically involve loss of function or modification of FCTs. This leads to the question, How do new adaptive FCTs arise? In two subsequent posts, I will discuss Behe’s review of FCT evolution in bacteria and viruses, as well as the implications he draws from that data.

    And here is Behe himself:

    I don’t “dismiss improved functions.” Rather, as I explicitly state, my focus is on distinguishing beneficial degradative mutations from beneficial constructive mutations. That is, do most beneficial mutations help by constructing new “functional coded elements” (abbreviated FCTs, — for example, genes or control elements) or by degrading old ones? That’s simply an exercise in counting the number of beneficial mutations that fall into each category. As I originally wrote in The Quarterly Review of Biology,32 by far the most frequent beneficial mutations reported in the literature are ones that degrade FCTs. — Sorry! Don’t blame me! That’s just the way it is.

    I’m sorry that I may have moved the conversation away from discussing LYST and back to APOB, but this might also be relevant to the function of LYST, I haven’t looked at that.

    All I see here is adjustments to existing FCTs to enable animals to survive in specific environments. Such narrowing of niches is never a good thing for long term survival.

    ETA – * This quote is from Casey Luskin.

  41. Rumraket: Behe ignores the “benign” mutations, and only shows the ones predicted to be “damaging”.

    If I understand correctly benign mutations are beyond the scope of his present inquiry. He is just looking at “damaging” in realition to “adaptive”.

    Rumraket: So for the LYST example the frequency of “damaging” mutations isn’t high enough for them to substantiate his rule.

    What must the ratio be in your opinion? It’s seems to me that anything above parity for “damaging” would be very interesting in what it says.

    peace

  42. fifthmonarchyman: I haven’t read the book yet but I think this is progress. Behe is not anti-evolution as I understand it. He just wants to quantify what evolution (ie RM/NS) can and can’t do and set boundries.

    No, that is misleading. The problem is that Behe takes his “first rule of adaptive evolution” to the conclusion that the molecular and functional complexity of life could not have evolved. But he does that by explicitly ignoring neutral molecular evolution, and by avoiding the phenotypic effects of molecular evolution.

    He focuses on molecular evolution (which is known to be mostly neutral) then simply ignores it by ONLY considering the molecular effects of adaptive mutations, which he have categorized such that many function and complexity increasing mutations are “modifications” instead of gains, and completely bypasses the physiologicl/phenotypic effects of mutations (to pick an example, Behe would consider the gain of antibiotic resistance a “loss of function” if it happened by deactivating a transporter gene), that way he can pretend that natural selection has nothing (or “too little”) to do with creating some of the apparent adaptations and functional complexity of life.

    The whole thing is extremely deceptive and it is challenging not to think this is done deliberately. Of course, he could just be sincerely but completely blinded by his religious convictions, I’m not going to rule that out.

  43. fifthmonarchyman: If I understand correctly benign mutations are beyond the scope of his present inquiry. He is just looking at “damaging” in realition to “adaptive”.

    Then you don’t understand correctly, because the “benign” mutations are among the selected mutations. In order for his claim that most adaptive molecular evolution is “damaging” to be true, he must show that most adaptive mutations are damaging. He can’t then just ignore the adaptive mutations that are “benign” to the protein’s function.

    This is what Entropy correctly points out when he shows the full list of adaptive mutations (and these are the MOST HIGHLY selected mutations) in the LYST gene. Behe has left out showing the “benign” mutations, but those actually have higher frequency (there are significantly more of them) than the “damaging” ones. So for the LYST gene example, his rule doesn’t hold. The majority of adaptive, highly selected mutations in the LYST gene are actually benign.

  44. With regard to Liu et al, Behe has done two things that are wrong.
    1) He has, whether by circumlocution or (in the case of LYST) the blatant error of referring to a singular as a plural, painted a deliberately misleading picture of the ratio of “benign” to “damaging” mutations in polar bear evolution.
    Stung into defending himself, he posted a mutilated table S7 at ENV (which omitted all “benign” mutations), with an inaccurate caption. His apologists have retreated to the position that that’s okay, because he provided a link to Liu. Hardly, given that Table S7 is buried as an Excel file in the supplemental materials.
    2) “benign” and “damaging” in Liu et al actually mean “unlikely to affect function” and “likely to affect function, whether in a positive or negative manner”, so he CANNOT use these data to support is argument about the relative contributions of GoF and LoF mutations in evolution.
    He has a separate, decade-old error, which is his insistence on a biochemist’s definition of GoF and LoF, and his campaign to sweep change of function mutations under the rug.

    I have been focusing on error (1) because understanding it does not require any knowledge of biology, merely the ability to count, and it is very difficult to maintain that it is a ‘honest’ mistake.

  45. CharlieM: But cholesterol is a substance which animals need and so it’s not a matter of efficient clearance that is important, it is a matter of maintaining the correct balance of cholesterol in the system. This efficient clearing would be detrimental to animals with a diet which is less fatty than that of polar bears.

    Uhh please cite the literature that shows this. Not buying it.

  46. Most of the molecular complexity of life actually begins as selectively (nearly) neutral expansions of parasitic genetic elements, such as retroviral insertions, introns, transposons, and then a whole lot of gene duplications.

    Of these, many slowly degrade over time and lose their functions. A significant portion of this “degenerative” change to endlessly copied genetic material and functional genes is adaptive, because the excess genetic material is technically “unneeded”, and has a slight metabolic cost. Occasionally, rarely in the big scheme of things, this accumulating molecular complexity takes on a novel adaptive function. But compared to how often this excessive and continously expanding genetic material “breaks”, it is much less frequent.

    Behe, because of how he has defined what counts as a gain, loss, and modification, can interpret the totality of this described process as one of “mostly adaptive loss” (which isn’t even correct, since it’s mosly neutral bricolage expansion). Yet he hasn’t shown that evolution can not or did not produce the complexity of life, he’s just invented a way of merely labeling it as “devolution”.

    IDiot fools are highly impressed of course. But we knew they’d be when the book was first announced. There’s nothing the DI propaganda mill can spit out they won’t gurgle and inhale with tearful glee.

  47. fifthmonarchyman: Darwinism with it’s emphasis on the random nature of change is what the people I hang with really object to.

    I think folks like Swamidass should be hammering the “Darwin is dead” meme. If they did it would do a lot to assuage the hostility to “evolution” in lay Evangelicals and perhaps bring a little peace to science

    Science is not in the business of appeasing religious wingnuts. BTW, for the emptienth time, if neutral theory “killed” darwinism, then what we now have is even more randomness. You don’t like it? welp, reality doesn’t care

  48. Rumraket:

    CharlieM: But cholesterol is a substance which animals need and so it’s not a matter of efficient clearance that is important, it is a matter of maintaining the correct balance of cholesterol in the system. This efficient clearing would be detrimental to animals with a diet which is less fatty than that of polar bears.

    Uhh please cite the literature that shows this. Not buying it.

    I just googled it and very quickly found this:
    Here

    Cholesterol is a type of fat that is part of all animal cells. It is essential for many of the body’s metabolic processes, including the production of hormones, bile and vitamin D. However, there’s no need to eat foods high in cholesterol. The body is very good at making its own cholesterol – you don’t need to help it along.

    And I like this quote here

    Researchers are beginning to understand in greater depth that the relationship between cholesterol and the body is extremely complicated.

    It seems the more they research, the more complexity they find. Who would have imagined that? I predict that this unearthing of greater complexity will continue to become apparent with all biological research.

    I’m sure there are more technical papers on the subject of cholesterol if you care to look.

  49. CharlieM: I just googled it and very quickly found this:
    Here

    Cholesterol is a type of fat that is part of all animal cells. It is essential for many of the body’s metabolic processes, including the production of hormones, bile and vitamin D. However, there’s no need to eat foods high in cholesterol. The body is very good at making its own cholesterol – you don’t need to help it along.

    But that has nothing to do with the tendency for excess LDL cholesterol to accumulate in the bloodstream. The fact that cholesterol is needed as part of the cell membrane does not mean it isn’t harmful in high quantities in the bloodstream. You understand the distinction here, right? Cholesterol in the cell membrane, vs cholesterol in the bloodstream. These are not the same thing.

    You have failed to support your rationalization, sorry.

    I’m sure there are more technical papers on the subject of cholesterol if you care to look.

    I’m sure there are, and that you’d have found one that supported your contention if you could. But you couldn’t.

  50. Here sciencedaily cites a study on LDL-C levels, but I don’t have access to it.

    June 27, 2016
    University of South Florida (USF Innovation)
    Summary:
    An international team of experts has found that older people with high levels of low-density lipoprotein (LDL-C) live as long, and often longer, than their peers with low levels of LDL-C. The findings, resulting from an analysis of past studies involving more than 68,000 participants over 60 years of age, call into question the ‘cholesterol hypothesis’ which suggests people with high cholesterol are at risk of dying and need statin drugs to lower their cholesterol.

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