On the improbability of our existence

There have been some great critical responses to some of the posts, which deserved a reply long ago. All the posts criticized involve either a chemical, molecular biological or numeric argument about the macromolecules making us up.  Here they are in a semi-logical sequence.  I’ll deal with the actual criticisms in the next post(s).

Two posts involve simple calculations about how many distinct proteins or polynucleotides life could have made given the mass of the earth to do so and 14 billion years.  Here are the links. (1) https://luysii.wordpress.com/2009/12/20/how-many-proteins-can-be-made-using-the-entire-earth-mass-to-do-so/ (2) https://luysii.wordpress.com/2009/12/28/how-many-distinct-rna-polymers-can-be-made-using-the-mass-of-the-earth-to-do-so/.

No one has criticized the correctness of the calculations, which show that life on earth could have made only an infinitesmal fraction of the possible proteins of only 100 amino acids, or polynucleotides of 100 bases.  If you disagree say so now.  There has been severe criticism of the implication that evolution works by randomly trying out all such possibilities.  I didn’t really say that, and will deal with this in the next post.  I do think that all of us agree that mutations occur randomly (recombination hotspots excepted) so that the grist for the evolutionary mill is formed essentially willy nilly.    If you disagree say so now. 

What I was really getting at, is that I find the proteins which make us up rather miraculous in that (1) they have one or just a few conformations which give then a fairly stable shape — they certainly do or we wouldn’t be here.  For details see http://luysii.wordpress.com/2010/08/04/why-should-a-protein-have-just-one-shape-or-any-shape-for-that-matter/.  (2) their side chains don’t react with each other.  For details see https://luysii.wordpress.com/2010/05/13/protecting-groups/. 

I think proteins with such magical properties are exceedingly uncommon.  So how would you know how common such proteins actually are ?  While possible in theory, the experiment to investigate the structures of a random sequence of amino acids is impossible to carry out fully.  For details see htts://luysii.wordpress.com/2010/08/08/a-chemical-gedanken-experiment/.  It still might give an answer if nearly every random sequence  of say 60 – 100 amino acids had just one or a few structures.  

I’m unimpressed with the argument that there are only 1000 or so protein folds, which significantly narrows the search space. There are huge numbers of proteins in the microorganisms living in the sea which far outnumber what we’ve already studied. Even if correct, how would random mutation find them?   I’d love to see the results of the ‘glass eye’ experiment — for details see http://luysii.wordpress.com/2009/11/29/time-for-the-glass-eye-test-to-be-inserted-into-casp/

Finally, I must admit that these speculations provided a certain degree of comfort as I watched patients I was unable to help get worse and worse and finally die.  For details see –http://luysii.wordpress.com/2009/09/17/the-solace-of-molecular-biology/. If our existence is as miraculous as I think it to be, then what really needs to be explained is not suffering and disease, but health and the gift of life.  At long last, a semi-answer to Camus “The Plague” which affected me profoundly as an undergraduate years ago.

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  • Galaxy Rising  On October 21, 2010 at 5:20 pm

    Wow, you really haven’t been paying attention at all.

    Mutations are not the MOST important part to the evolutionary process. They add variety, yes, which means they are especially important in SMALL populations, but in the evolutionary “equation”, they are often exceptionally underwhelming in importance.

    They are NOT formed willy nilly; this is an ABSURD statement if I’ve ever heard one! They are SELECTED (in a variety of ways that we know of) based in fitness. In the simplest and most ancient cases, they are selected by ACTIVITY. More activity, more helpfulness, more of them made, more variants made (via mutation and error prone reproduction), more probability of IMPROVING that activity. This is known as a DEPTH FIRST SEARCH with KILLER HEURISTIC, you may read about it in any computer science textbook: searching is done where it is already know activity occurs, not at random.

    This is the entire principle of natural selection; read a biology or computer science textbook, and you’d recognize this.

    Because of this selective process based off of a fitness function, natural selection as well as other forms of evolution have been mathematically abstracted, and are used in computer science to search spaces just as large, if not larger, than the protein space. Protein space only increases linearly in complexity, where as many problems in CS increase polynomially or exponentially, yet have good heuristics for finding good solutions quickly.

    What I am saying, in a nut shell, is that you are forgetting mutation is a PART of the process, not THE PROCESS. The other parts are just as or more important.


    Do try and read up before you make statements which make no sense in biology, mathematics, or computer science.

    • luysii  On October 21, 2010 at 6:27 pm

      We continue to talk past each other. What do you think I mean by “grist for the evolutionary mill” ? The evolutionary mill is, of course, natural selection. This occurs in all of us as antibodies mature and, unfortunately, in HIV+ patients as the virus mutates to defeat the immune system.

      Do you think that mutations arise NONrandomly?

      • Galaxy Rising  On October 21, 2010 at 11:25 pm

        Selection most definitely does not occur randomly; the fact mutations are random does not make the process as a whole “willy nilly”, or random, only probabilistic. You are making a misleading and straw man statement.

  • Galaxy Rising  On October 21, 2010 at 5:35 pm

    Note, if you will, this statement: “GA’s (genetic algorithms) can often find good solutions, even for large search spaces”.

    This is, in fact, a blanket statement that can fit onto ANY evolutionary optimization approach; good solutions can be found rapidly, even if optimal ones cannot be found at all. And biologically, many proteins are less than ideal, but conserved by this very fact.

    Biology proves the approach; mathematics proves it works.

    • luysii  On October 21, 2010 at 6:38 pm

      Natural selection can only work on the variants that mutations (of all sorts) present it with. The next post will explain my thinking as to why the number of variants has been inadequate to explain life. Hold off till then.

      • Galaxy Rising  On October 21, 2010 at 11:28 pm

        Natural selection is not the only evolutionary mechanism. Neutral selection, for example, has a much larger mutation rate, allowing it to be the generator for natural selections optimization.

        Pulling a piece of evolutionary science and examining it in a clean room, with no perspective is just as misleading as thinking combinational mechanics (that is, selecting a single combinations from all permutations) is at all relevant. They work together, and are optimized for particular tasks.

  • luysii  On October 22, 2010 at 7:43 am

    ”Sir, I have found you an argument; but I am not obliged to find you an understanding.”
    – Samuel Johnson

    Of course natural selection is not random. I never said it was (did anyone?). Neutral selection is certainly another way of producing grist for the evolutionary mill. Please wait until the next post.

  • Wavefunction  On October 23, 2010 at 9:51 pm

    I am late to the party but will wait for your next post. But referring back to your earlier one, you asked why side-chains of amino acids don’t interact deep inside a protein. The answer could have to do with the hydrophobic nature of the protein interior. The kind of reactions the side-chains can participate in require a build-up and transfer of charge (for instance, nucleophilic attack of water on an amide carbonyl builds up charge on the oxygen). Such charge buildup would be very heavily disfavored in the hydrophobic environment. That’s why even hydrogen bonds formed inside protein interiors are much stronger, because they cannot afford to not form.

    • luysii  On October 24, 2010 at 7:51 am

      Every neuron in your body contains a large number of voltage gated ion channels (some for sodium, some for potassium, others for calcium). The ones we know about have 6 alpha helices spanning the neuronal membrane (numbered S1 – S6). There is also part of the channel between S5 and S5 which loops in from the outside of the neuron and then loops back. It forms part of the pore wall of the ion channel. The voltage sensor is thought to be S4 which contains 4 arginines all one one face of the S4 helix. 2 of the arginines bind to anionic amino acids on another helix. When voltage across the membrane changes, the S4 helix is thought (by Catterall (in his sliding helix model) to twist and move into or out of the membrane (depending on which way the voltage across the membrane is changing) closing or opening the ion channel by tugging on the S5 and S6 helices (which with an intervening loop actually form the channel part of the protein). Regardless of the position of S4, Two of the arginines are always bound to the same two anionic amino acids, stabilizing each position of the S4 helix. Exquisite, no?

      So here is an example of multiple charged amino acids within a protein absolutely crucial to its function. Moreover the protein itself is found in the extremely hydrophobic environment of a lipid membrane.

      For an excellent review of Catterall’s model (with good pictures) by the man himself see Neuron vol. 67 pp. 915 – 928 ’10.

  • Wavefunction  On October 25, 2010 at 7:10 am

    The voltage gated ion channel is indeed wonderful, but there’s still no chemical reaction taking place. In this case nature has designed a very specific case for a specific purpose. I really doubt that you could generally observe many enzymes which conduct reactions deep inside a lipophilic pocket.

  • Wavefunction  On October 25, 2010 at 11:15 pm

    Also, in the ion channel the charge is neutralized by the side chains pairing up so it’s not much of an issue.

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