The Case for Cell-Directed Mutations

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I recently created a video (sorry, it’s a long one) covering what I view as the evidence that cells direct their own evolution. I’m curious what feedback others have on it.

Sorry about the length, but I cover a large number of topics, and try to explain it in light of all of the misunderstandings about the subject which I have seen.

88 thoughts on “The Case for Cell-Directed Mutations”

  1. johnnyb: While these are not incontrovertible, these are actually fairly standard numbers coming from the standard literature.

    No, they’re not. They’re a cherrypicked range at the lower end of the range of estimates. With the highest number being cherrypicked to still be low, to make it seem like anything above that is absurd. And I don’t buy for one goddamn second it wasn’t done deliberately for that very purpose. Lying for Jesus, the oldest trick in the book.

  3. T_aquaticus: A gambler purposefully rolls the dice in the game of Craps. The results of that roll are still random with respect to the chips on the table. This is analogous to “directed” mutations.

    So in this analogy the organism purposely “rolls” the mutations without knowing why?

  4. petrushka: I would simply say that Sanford ignores the fact that genetic meltdown doesn’t happen. His model is wrong. Bumblebee’s do fly.

    If bumble bees were created last thursday there is no reason to expect a genetic meltdown today.

  5. DNA_Jock: Far be it from me to speak for Rumraket, but he has a track record of knowing what he’s talking about…

    Except when it comes to Napoleon in Russia.

  6. Rumraket: In any case, when we speak of random mutations we are of course not saying mutations happening without some physical cause.

    Why not? It is my understanding that you don’t have an issue with events without causes. Not sure how science is supposed to work in that scenario. It smacks of supernaturalism.

  8. DNA_Jock: I will note that science cannot rule out the possibility that a God-like designer is responsible for every single mutation that occurs.

    I agree.

  9. Mung: Why not?

    Because we know chemical and physical causes of mutation. Why would we then say they are uncaused?

    It is my understanding that you don’t have an issue with events without causes.

    From what did you get that impression?
    I’ll tell you my problem with it: I don’t see how we could ever establish that something was truly uncaused. It might be the case that some things are, but how would we know?

    Not sure how science is supposed to work in that scenario. It smacks of supernaturalism.

    Well if supernaturalism means that things have no causes then I agree, and one could not do science on it. But does it? Are supernatural entities or events by definition uncaused? How do I confirm that they are?

  11. Mung: Recent comments of yours at PS.

    Not sure which ones you are talking about. I do remember having commented on something about causes, I just don’t remember having said something that should cause you to get that impression.

    In any case, I’m really just trying to say that I don’t have some sort of a priori commitment to a particular view of causality. My issue is primarily epistemological. I want to find out what is true without being prejudiced against any potential discoveries, but I see a big challenge in finding that out for certain hypothetical problems. “It is difficult to find out what the cause is”, does not suffice in my opinion, to substantiate the claim that phenomenon X actually was uncaused.

    I do think though as a practical matter that assuming that events have detectable causes is conducive to science. But whether those practical assumptions correctly reflect reality in any and all circumstances I cannot say. It is at least conceivable that there are certain phenomena that occur spontaneously without a cause. Some people will claim that certain quantum phenomena are uncaused, I just don’t see how they can claim to know that. If you ask them, they will respond that “but we don’t find any”. Perhaps that really is a piece of evidence for something without a cause, perhaps they just haven’t got the tools necessary to detected them. I don’t know is all we can really say as far as I am concerned.

  12. Rumraket: And yes there are documented cases of mutations happening according to my latter case of directed. As in directed by a highly specific, “targeted” but ultimately blind biochemical process.

    Well, that clears things up for me! 🙂

  13. Alan Fox

    Rumraket: And yes there are documented cases of mutations happening according to my latter case of directed. As in directed by a highly specific, “targeted” but ultimately blind biochemical process.

    : Well, that clears things up for me!

    If only it were that simple! 🙂

  14. From one of the links provided by johnnyb:

    But now, with complete genome sequences before us, instead of triumph comes humility…

    Chapter 15 describes the Drosophila Dscam gene, a single gene that, at least theoretically, can, by alternative splicing, generate three times as many proteins as there are protein-coding genes in the genome…

    The distinct tilt and twist of different steps of stacked base pairs along the helix may tend to average out, but for sequences highly enriched in one base, or in which a sequence motif is repeated, there can be substantial deviations from the average coordinates that are used in text-book models of the double helix. The biological consequences of such sequence-dependent variation in DNA structure are discussed in several chapters of this book.

    For example, as described in chapter 13, sequences that s described in chapters 4 and 12, repeats of sequences may favor or inhibit nucleosome assembly, with effect both on gene expression and on the likelyhood of genetic exchange between two parental genotypes at that site during meiosis.

    As described in chapter 1, protein binding to DNA can be affected by effects of DNA sequence on backbone geometry, In fact, changing the sequence of a four-base “spacer” between two binding sites can change protein affinity by over three orders of magnitude. Similarly, the nature of the spacer sequence affects the efficiency of recognition of immunoglobin recombination signal sequences, as referenced in chapter 9.

    It seems that the more we know the more we realise how complex these things are and how much there is still awaiting to be discovered. There is nothing simple about genetics. Humility is indeed called for.

  15. Rumraket: . Some people will claim that certain quantum phenomena are uncaused, I just don’t see how they can claim to know that. If you ask them, they will respond that “but we don’t find any”. Perhaps that really is a piece of evidence for something without a cause, perhaps they just haven’t got the tools necessary to detected them. I don’t know is all we can really say as far as I am concerned.

    Rum,
    You don’t know anything about quantum mechanics….When you do know or learn enough about it, you have two options only:
    You will likely go crazy or you will never be the same again…
    Which one would you prefer?

  16. Alan Fox: Well, that clears things up for me! 🙂

    Bravo! The evidence for blindness still pending… and pending, and pending… and will continue to pend… but it sure made Alan happy… Who needs a Bimmer 8 to feel happy? The reassurance of nonsene will do…

  17. Rumraket: That you ask your nearest adult to help restrict your internet time at wherever you are currently institutionalized. And that you resurrect your regiment of anti-psychotics.

    Fair enough!
    You know what to do to ingore people like me, right?

  18. Mung: Why not? It is my understanding that you don’t have an issue with events without causes. Not sure how science is supposed to work in that scenario. It smacks of supernaturalism.

    Great catch mung!
    You good you! lol

  21. To be clear on my comment about QM: scientists have been able to detect effect before cause… The uncaused cause is a separate issue which, as far I can recall, is inferred from equations of quantum mechanics that allow the infinite number of dimensions… but I might be wrong about it…

  22. Mung: So in this analogy the organism purposely “rolls” the mutations without knowing why?

    Cells don’t consciously know that they are producing mutations. What I was conveying is the idea that purposeful and random are independent concepts. You can purposefully create a random sequence.

  23. johnnyb:
    Alan Fox,
    There are many other, similar processes, but I like to use somatic hypermutation because it is relatively unambiguous what is happening, and has been rigorously studied for almost half a century now, so there is little doubt as to the details.

    Limiting random mutations to a section of the genome does not stop them from being random mutations.

  24. CharlieM: IMO this is a poor analogy.

    A better way of putting it would be: All the gamblers that throw the dice at that table suffer any losses personally but donate whatever winnings they get towards the communal good. So we have losses at a lower level but gains at the higher level.

    A similar analogy would be the seeds of a dandylion. The seeds are scattered randomly or if you prefer haphazardly, and there are more lost than produce new plants. The losses are unimportant, it is the few that germinate that ensure the continued existence of the species. And of course any that are lost to the plant are of benefit to various other species. Individual seeds may be destroyed before they can produce more dandylions, but overall, life gains from the destruction.

    Just because some mutations are beneficial does not mean they were guided or directed. You can still win the lottery by randomly picking numbers.

  25. T_aquaticus,

    Limiting random mutations to a section of the genome does not stop them from being random mutations.

    Correct. What makes it non-random is that this limitation pretty much exactly coincides with the biological necessity. If you know of a better definition of non-random mutation than a mutation which is carried out by specific enzymes acting at specific times when needed whose range coincides with biological necessity, let me know what you think the definition should be.

  26. johnnyb: If you know of a better definition of non-random mutation than a mutation which is carried out by specific enzymes acting at specific times when needed whose range coincides with biological necessity, let me know what you think the definition should be.

    Interesting…But how do the enzymes know the exact timing to act?

  27. johnnyb:
    T_aquaticus,

    Correct.What makes it non-random is that this limitation pretty much exactly coincides with the biological necessity.If you know of a better definition of non-random mutation than a mutation which is carried out by specific enzymes acting at specific times when needed whose range coincides with biological necessity, let me know what you think the definition should be.

    Those mutations still produce detrimental and neutral changes, along with beneficial mutations.

    A better definition of non-random is a specific mutation at a specific base being produced in direct response to a specific environmental trigger. For example, if you exposed bacteria to an antibiotic and every single bacteria mutated the very same base that conferred antibiotic resistance, and only through a serious of signalling peptides that detected the antibiotic, then this would be a non-random mutation. This is what biologists would consider a non-random mutation.

  28. T_aquaticus,

    So, just to be clear, unless a mutational process produces the *exact* right sequence change the *first* time, it is not a directed mutation in your book? Let’s say that the mutational process reduced the number of possible mutations to 3. According to your standard, that is not directed since the majority of mutations would be neutral or deleterious.

    In the case we are describing, the reduction in mutation space is from 3,000,000,000 to 1,000. This corresponds to the biological need. It is the correct half of the correct gene that needs to be mutated. It doesn’t know the exact sequence, but it does know that it needs to be within this space. The mutations occur entirely within this space.

    Note also that this is an order of magnitude reduction. The average number of mutations needed is about 3. Finding the right set of 3 mutations in 3,000,000,000 base pairs vs. 1,000 base pairs is about 20 orders of magnitude different.

    Biology is almost never about exactness, it is about continuities and cutoffs. I have trouble seeing how the argument works for why a process which is 20 orders of magnitude more directed than random still counts as random.

  29. johnnyb:
    T_aquaticus,

    So, just to be clear, unless a mutational process produces the *exact* right sequence change the *first* time, it is not a directed mutation in your book? Let’s say that the mutational process reduced the number of possible mutations to 3.According to your standard, that is not directed since the majority of mutations would be neutral or deleterious.

    In the case we are describing, the reduction in mutation space is from 3,000,000,000 to 1,000.This corresponds to the biological need.It is the correct half of the correct gene that needs to be mutated.It doesn’t know the exact sequence, but it does know that it needs to be within this space.The mutations occur entirely within this space.

    Note also that this is an order of magnitude reduction.The average number of mutations needed is about 3.Finding the right set of 3 mutations in 3,000,000,000 base pairs vs. 1,000 base pairs is about 20 orders of magnitude different.

    Biology is almost never about exactness, it is about continuities and cutoffs.I have trouble seeing how the argument works for why a process which is 20 orders of magnitude more directed than random still counts as random.

    It is about both the number of mutations and the mechanisms that produce the mutations. What is the physical connection between the specific mutations and the specific environment.

    Let’s use somatic hypermutation as a part of B-cell amplification and antibody production. When a B-cell is stimulated to make more antibody it tends to increase the mutation rate in the genes responsible for the antibody it produces. But how does the B-cell “know” which mutations will increase antibody specificity and avidity? Well, it doesn’t. There is no mechanistic connection between fitness and mutation. They are still independent of one another.

    Randomly mutating a section of the genome is still random mutation.

  30. johnnyb: So, just to be clear, unless a mutational process produces the *exact* right sequence change the *first* time, it is not a directed mutation in your book?

    Yeah pretty much.

    If up to 16% of mutations are adaptive in novel environments, as one literature reference suggested, that’s still 84% of mutations being nonadaptive. Of what use is it to describe that process as “directed”? It seems to me it’s still just random mutations blindly sampling a solution space until something that improves reproductive success emerges.

  31. johnnyb: Let’s say that the mutational process reduced the number of possible mutations to 3.

    So when I toss a coin, the result is not random because the number of possibilities is reduced to two?

    I would never have guessed.

  32. T_aquaticus: Just because some mutations are beneficial does not mean they were guided or directed.You can still win the lottery by randomly picking numbers.

    It’s odd that people one would expect to be familiar with the Parable of the Sower don’t buy this. Of course, the Sower had a purpose, but still implemented it by random scattering.

  35. Hey Johnnyb,

    I have been watching your very intriguing video…
    I have a question before I forget. You mentioned something about preexisting mutations or mutations occurring beforehand, as if preplanned or predetermined…
    Are they the same thing as an antibiotic resistance mutation happening before antibiotics were even developed?

  37. Rumraket: What idea, specifically?

    From Koonin’s paper:
    The description of the CRISPR-Cas, piRNA and some forms of HGT as (quasi)Lamarckian phenomena has been criticized, firstly, because this description seems valid only when the organismal level of selection is considered (Poole 2009) and secondly, because historically, Lamarckian evolution implies a teleological character of evolution (Weiss 2015). Both these criticisms indeed address major aspects of the evolutionary process but both appear to be readily answerable. As discussed above, the (quasi)Lamarckian phenomena are based on evolved mechanisms that could only emerge in relatively complex life forms, such as the first cells (Koonin and Wolf 2016). These mechanisms have nothing to do with teleology but rather emerged under the pressure to evolve efficient phenotype evolvability by biasing the mutational process and restricting mutations to specific genomic loci.

    Might be Koonin’s use of “(quasi) Lamarkian” in titles.

  38. Alan Fox: From Koonin’s paper:
    The description of the CRISPR-Cas, piRNA and some forms of HGT as (quasi)Lamarckian phenomena has been criticized, firstly, because this description seems valid only when the organismal level of selection is considered (Poole 2009) and secondly, because historically, Lamarckian evolution implies a teleological character of evolution (Weiss 2015). Both these criticisms indeed address major aspects of the evolutionary process but both appear to be readily answerable. As discussed above, the (quasi)Lamarckian phenomena are based on evolved mechanisms that could only emerge in relatively complex life forms, such as the first cells (Koonin and Wolf 2016). These mechanisms have nothing to do with teleology but rather emerged under the pressure to evolve efficient phenotype evolvability by biasing the mutational process and restricting mutations to specific genomic loci.

    Might be Koonin’s use of “(quasi) Lamarkian” in titles.

    Koonin MUST have at least SOME experimental evidence to prove all the “quasi specualtion” of pressures that sound more like science fiction and less like science…

    Why pays for this nonsense?

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