cumulative selection part III

From: Josh Bembenek (
Date: Sat Aug 10 2002 - 16:25:50 EDT

  • Next message: Josh Bembenek: "cumulative selection part IV"

    > "And it was doing it in a life form which didn't _need_ oxygen carried,
    > much. It lived in the ocean and it preceded the divergence of plants and
    > animals. It didn't exactly have four-chambered heart, and lungs, and
    > capillaries. We know this because globins are found so universally, in
    > lifeforms both with and without blood."

    > ---This may certainly free the restraints required for hemoglobin
    > If it was originally only marginally required and only marginally
    > advantageous to the organism, then it may have had more chance to get
    > Do you think that this is globally applicable? It would seem that
    > are many functions within the machinery necessary for life that cannot be
    > minimized back to a time when they weren't required or important. The
    > organisms may not have needed globins very much, but they certainly
    > upon thousands of other critical enzymes for their survival and
    > reproduction. For these other critical enzymes, was there also some
    > unnecessary timepoint where they could be evolved and yet not required?
    > so, this would imply that every product made by every enzymatic pathway
    > critical for life was available for the first cell/replicative code to
    > before the enzymes capable of producing them existed. Is there any
    > to think this is correct? How could we prove/disprove this assertion?

    Yawn. Abiogenesis is not my department, nor do I subscribe to the theory
    that if we don't know everything yet, then it's time to despair. I
    decline to let you move the goalposts every time I succeed at answering a
    question. (We discussed globin: now you want me to explain thousands of
    things, and I suppose your doubts are alive until *every* *last* *one* is
    convincing.) And I consider it fallacious that Intelligent Design people
    try to deal only in things that happened *more* than a billion years ago.
    What, God went away a billion years ago? Or are they merely trying to
    cover up the fact that when something happened recently enough for the
    evidence to still be around, the evidence displease them?

    {Note} He is minimizing the problems with his unsupported claims and
    arguing a strawman. Since he cannot actually provide a direct answer to the
    issue of products needed for a cell before the enzymes capable of producing
    them exist, he avoids it and gets defensive. Just because hemoglobin was
    "not needed much" does not eliminate the overwhelming problems indicated
    below about deriving hemoglobin sequences, here I was simply agreeing that
    it would "help" if it were "not needed much." Not being needed much,
    therefore, does not give us anything close to a mechanistic answer or much
    insight into the problem. Nor is it something supported by factual
    published evidence in peer-reviewed journals. No one has proven just how
    much (I wonder what your assay would be for degree of need) simpler
    organisms may or may not need their particular hemoglobin molecules, they
    could be very important for organism survival. The citations he provided
    show the original discovery of these "derivative" hemoglobins. I don't
    believe it is currently understood how essential they are, he certaintly
    doesn't cite anything, simply dogmatically declares his faith.

    {Note} What follows is the body of the original message without any further
    comments from Dr. Lindsay as I wrote it to him in response originally:

    > "Well, some act as oxygen binding/inactivation proteins - as occurs today
    > some bacteria. Those probably evolved from hemoglobins that did electron
    > transport. And sure enough, some modern bacteria use them for just that.
    > Specifically, the electron transport carrier cytochrome B family. And
    > there's nitric oxide:"

    > ---I see the issue in this way, all globins have the same fold and
    > identity. There is nothing obvious to me about the relationship between
    > the globins that give indications as to how the globin fold itself ever
    > evolved. There is a point in sequence identity before which any given
    > sequence can adapt the globin fold, and previous to it being a globin I
    > not understand how this hypothetical protein would have function or even
    > fold properly. All the papers you listed highlight the fact that all
    > genes, while they may vary as much as 80% of the positions (leghemoglobin
    > vs. vertebrate globin in Hardison, R. C., PNAS 93, 5675-5679) maintain
    > same three-dimensional structure, have specific residues that are highly
    > invariable, and additional restraints for certain portions of the
    > to remain hydrophobic, etc. for the globin to be intact! From the
    > mentioned, not only do all globins share three dimensional structure
    > similarities, but they all share the ability of binding oxygen, with some
    > members gaining additional functionality. My question about this issue
    > ignores the ability of a given protein to perform a given function and
    > additional functions, rather my question is focused on how do you drive
    > formation of the original function in the absence of the ability to
    > that function to any degree whatsoever, BY MEANS OF DARWINIAN EVOLUTION
    (which supposedly is the generally accepted and proven mechanism for
    biological change)? When you are randomly synthesizing a globin molecule by
    way of randomly connecting amino acids or sequences, and you only have part
    of the globin
    > molecule in your sequence, it does not appear that it can provide any
    > selective advantage towards carrying oxygen before it is capable of
    > into a globin fold. To clarify my thinking on this issue, here is a
    > relevant section from "Biochemistry" by Lubert Stryer (p. 418):
    > "The way out of this dilemma is to recognize the power of cumulative
    > selection. Richard Dawkins, in The Blind Watchmaker, asked how long it
    > take a monkey poking randomly at a typewriter to reproduce Hamlet's
    remark to Polonius, "Methinks it is like a wasel." An astronomically large
    number of keystrokes, of the order of 10^40, would be required. However,
    suppose that we preserved each correct character and allowed the monkey to
    retype only the wrong ones.
    > In this case, only a few thousand keystrokes on average would be needed.
    > crucial difference between these cases is that the first employs a
    > completely random search [the hemoglobin number] whereas in the second,
    > partially correct intermediates are retained. The essence of protein
    > folding is the retention of partially correct intermediates. However, the
    > protein folding problem is much more difficult that the one presented to
    > simian Shakespeare. First, proteins are only marginally stable. The
    > free-energy difference between the folded and unfolded states of a
    > 100-residue protein is 10kcal/mol. The average stabilization per residue
    > only 0.1kcal/mol, which is less than random thermal energy
    > at room temperature). This means that correct intermediates, especially
    > those formed early in folding, can be lost. The analogy is that the
    > would be quite free to undo its correct keystrokes. Second, the criterion
    > correctness is not a residue-by-residue scrutiny of conformation by an
    > omniscient observer [as Dawkins analogy provides with the computer
    > but rather the total free energy of the transient species. Intermediates
    > be scored only by their free energies. Third, some intermediates, called
    > kinetic traps, have a favorable free energy but are not on the path to
    > folded protein form. No wonder then that protein folding is such an
    > intriguing problem for both theoriticians and experimentalists."
    > In sum, this indicates that the restraints for the development of even a
    > simple globin fold would be enormous. The number of counterproductive,
    > unfolded, disadvantageous sequences that stand in between any given
    > sequence and the first functional advantageous globin molecule seems
    > large. Dawkins analogy closes its eyes as the initial random sequence
    > traverses these dangerous protein folding intermediates and kinetic
    > favorable non-folded traps, and completely ignores the technical
    > involved with creating a folded, soluble protein, much less originating
    > fold capable of properly binding a porphyrin ring! The analogy also
    assumes that each such intermediate has selective advantage in the
    replicating system it is a part of. Obtaining a protein
    > molecule capable of binding any porphyrin ring (ignoring whatever
    > are required to synthesize the first porphyrin ring so that it would be
    > available for use when the ancient precursor porphyrin-ring-binding
    > serendipitously emerged from the chaotic world of
    > non-functional-protein-folding intermediates) must be an enormous feat
    > on its own. What evidence or indication makes such a scenario possible?
    > Protein folding issues indicate to me that the origin of functional
    > is beyond the ability of random sequence generation and slight sequence
    > modification until the final functional sequence is happened upon,
    > there is no utility for these intermediates. (Hence my curiosity for the
    > support of your previous statement that hemoglobin was doing something
    > but not very well on its way to becoming hemoglobin.) If anything, this
    > process would create many more molecules that inhibit the process rather
    > than augment it taking into account these issues from protein folding
    > dynamics. The range of theoretical "optimized multiple desirable
    > seems quite narrow within the possibilities, but similarly the sequence
    > space that needs to be traversed from random sequence to functional
    > seems even more limited with all the kinetic-trap pitfalls and non-folded
    > products. For similar reasons, the following statement you made:
    > <First, function is more mutable than you imagine.>
    > Does not correlate well in my mind with the above section from Stryer.
    > only do the examples you listed for highly mutable proteins with diverse
    functionality involve proteins that already have a given
    > stable fold, but as far as I am aware, they are rare occurrences. Allen
    > remarks in his criticism of Behe's work, that (Boston Review @
    > ):
    > "First it will do no good to suggest that all the required parts of some
    > biochemical pathway popped up simultaneously by mutation. Although this
    > "solution" yields a functioning system in one fell swoop, it's so
    > unlikely that no Darwinian takes it seriously. As Behe rightly says, we
    > nothing by replacing a problem with a miracle. Second, we might think
    > some of the parts of an irreducibly complex system evolved step by step
    > some other purpose and were then recruited wholesale to a new function.
    > this is also unlikely. You may as well hope that half your car's
    > transmission will suddenly help out in the airbag department. Such things
    > might happen very, very rarely, but they surely do not offer a general
    > solution to irreducible complexity."
    > So it appears that Dr. Orr disagrees with the ability of proteins to be
    > evolved for "some other purpose and were then recruited wholesale to a
    > function," as you have described, and concludes that the occurrence of
    > i.e. proteins being recruited for new function, occurs "very very
    > What evidence or resource could I investigate to find a conclusion for
    > matter one way or the other? I tend to agree with Dr. Orr, but I would
    > highly interested in what evidence compells you to view the issue
    > differently.
    > In closing, consider the following sequence of events:
    > Completely Random Sequence (no function)
    > --Transition I-->
    > Stably folded, biologically active sequence (with function)
    > --Transition II-->
    > Optimized Diversity of Function derived from similarly folded sequences
    > You have argued that evidence from the second transition; i.e. the
    > generation of diversity of function from an original stable protein fold
    > proves that the first transition occurred. I would be very interested in
    > learning of the evidence or proof that exists directly demonstrating the
    > occurrence of the first transition. So far, what I've seen consists of
    > computer/ mathematical models, which do not directly relate to the
    > of protein folding and functional sequence intermediates (and are also
    > extremely clear to me on first investigation and therefore beyond my full
    > comprehension). This is the core of my skepticism of Dawkins' analogy
    > the fundamental problem I have envisioning how this scenario could occur.

    MSN Photos is the easiest way to share and print your photos:

    This archive was generated by hypermail 2.1.4 : Sat Aug 10 2002 - 17:24:12 EDT