Random origin of biological information

From: pruest@pop.dplanet.ch
Date: Sun Sep 24 2000 - 03:19:09 EDT

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    Glenn Morton wrote (Fri, 22 Sep 2000 18:11:13 -0500 (CDT), Random chance
    brings meaning, in part):

    >>> It is NOT cheating when the main point was that when people say that random sequences can't produce meaning it is clear from these examples, NO MATTER HOW RARE THE PHENOMENON, that meaning is generated from two random sequences. Just because there is randomness in a system doesn't mean that it can't produce meaning. While much discussion has proceeded, that simple fact was my main point. Randomness does not preclude meaning or semantics. <<<


    You are right, there IS randomness in all these 21-letter sequences, no
    matter whether they were generated by encrypting a meaningful phrase or
    by running a random number generator, and ANY meaningful 21-letter
    message can be generated from ANY of the 26^21 possible sequences if the
    right key is found.

    But this fact does NOT imply that meaning or semantics can arise
    spontaneously by random processes, without some intelligent input of
    information. Either this happens when the sender encrypts his message
    and gives the key to the designated receiver, or when an eavesdropper
    searches for meaning, using very much intelligence and effort in the

    Do such encrypted messages really tell us anything about the process of
    evolution? There, we have a random number generator alright, and we have
    natural selection. But for finding meaning, natural selection isn't as
    patient and powerful as an intelligent cryptographer with his computer.
    In the evolutionary process, the only possible natural source of
    information is the environment. But the extraction of this information
    is extremely slow, probably only a fraction of a bit per generation -
    when any useful mutants are available at all. And if they are, they must
    penetrate the entire population before being fixed. For small selective
    advantages and large populations, the mutation still risks being lost by
    random drift.

    If we compare this process with the huge amount of information in
    today's biosphere, I'm pretty sure 4 billion years is by far too little
    time. It is estimated that about 1000 different protein folds exist in
    living organisms, comprising about 5000 different protein families (Wolf
    Y.I., Grishin N.V., Koonin E.V. "Estimating the number of protein folds
    and families from complete genome data", J.Molec.Biol. 299 (2000),
    897-905). When we compare the prebiotic Earth with today's biosphere as
    a whole, each of these folds, families and individual proteins with
    their functions had to arise at least once somewhere. There is NO
    evidence that all or most of them could be derived from one or a few
    initial sequences through step-by-step mutation, each of the
    intermediates being positively selected, and this within a few billion

    In my post, I was discussing the evolution of functional proteins in a
    DNA-RNA-protein world, not evolution in an RNA world. I never talked
    about ribozymes (I did mention ribonucleases, but these are protein
    enzymes). I know about the in vitro selection of functional ribozymes,
    but I do not consider these as valid models of evolution at all. They
    just are techniques for finding active ribozymes among as many sequences
    as possible. Of course, mutagenizing steps generate new diversity, but
    the selection procedures most certainly are NOT natural. What we can
    learn from some of these experiments is the frequency of a given
    ribozyme activity among the pool of RNA sequences supplied (which
    usually is just a very tiny sample of all possible sequences, and of
    unknown bias).

    Further problems of the ribozyme work are: (1) Usually artificial
    "evolution" tapers off at activities several orders of magnitude lower
    than natural ribozymes (not to speak of protein enzymes) (cf. Bartel &
    Szostak, Science 261, 1411). (2) We don't yet know whether there ever
    was an RNA world. (3) We don't know whether it would be viable at all.
    (4) We don't know how it could have arisen by natural processes. Leslie
    E. Orgel, one of the pioneers in this field, wrote (Trends Bioch.Sci. 23
    (1998), 491):

    "There are three main contending theories of the prebiotic origin of
    biomonomers [1. strongly reducing primitive atmosphere, 2. meteorites,
    3. deep-sea vents]. No theory is compelling, and none can be rejected
    out of hand ... The situation with regard to the evolution of a
    self-replicating system is less satisfactory; there are at least as many
    suspects, but there are virtually no experimental data ... [There is] a
    very large gap between the complexity of molecules that are readily
    synthesized in simulations of the [suspected] chemistry of the early
    earth and the molecules that are known to form potentially replicating
    informational structures ... Several alternative scenarios might account
    for the self-organization of a self-replicating entity from prebiotic
    organic material, but all of those that are well formulated are based on
    hypothetical chemical syntheses that are problematic ... I have
    neglected important aspects of prebiotic chemistry (e.g. the origin of
    chirality, the organic chemistry of solar bodies other than the earth,
    and the formation of membranes) ... There is no basis in known chemistry
    for the belief that long sequences of reactions can organize
    spontaneously - and every reason to believe that they cannot."

    Against this background, I think it is moot, at present, to speculate
    about the probabilities of evolutionary steps in an RNA world. We DO
    know, on the other hand, how the microevolutionary mechanisms work in
    our world. This is why I chose to deal with this only, rather than with

    You are right in pointing out that Yockey revised his probability
    estimate for cytochrome c (now iso-1-cytochrome c) in his book
    "Information theory and molecular biology" (Cambridge: Cambridge
    Univ.Press, 1992). On p.254, he gives the probability of accidentally
    finding any one of the presumably active iso-1-cytochromes c as 2 x
    10^(-44), which is 21 orders of magnitude better than his 1977 estimate
    for cytochrome c. But I think most of this difference is NOT due to new
    experimental evidence (e.g. new sequences), but to his refined
    calculating method, taking into account adjusted probabilities for the
    individual amino acids, to find their "effective number", so it is
    hardly likely that this new estimate will increase any more. As 10^(-44)
    is still much too low to be of any use, I didn't think it worth while to
    try to present his much more complicated new procedure.

    One problem which remains is his assumption that there are no
    interdependencies between the different amino acid occupations within
    the sequence. On p.141, he even cites one observed case where the
    equivalence prediction of his procedure fails. We don't know how many
    more there are. Such interdependencies would reduce the overall
    probability massively.

    Furthermore, Yockey deals with modern cytochromes c (and some artificial
    derivatives) only, which are the result of a few billion years of
    optimization. A "primitive" enzyme may be more easily accessible. The
    only reason I quoted him was that we have NO information about ANY
    "primitive" enzyme.

    The important point is to find cases where natural selection does NOT
    work (yet), because then only we can do meaningful probability
    calculations, which apply only to random walks without selection of
    intermediate steps. The case I considered was the origin of a new
    enzymatic activity which did not exist before (anywhere in the
    biosphere, e.g. a new one of those 1000 folds, and using wildly
    over-optimistic assumptions). As soon as a minimal activity has arisen,
    natural selection can attack and speed up evolution by unknown amounts.
    This is another reason why the artificial ribozyme selection experiments
    are irrelevant in this connection.

    By the way, I would still be very interested to hear any comments about
    the model I calculated, from you, Glenn, or anyone else!

    In both of the cases you quote, an initial catalytic activity of the
    type selected for was present initially (gamma-thiophosphate transfer in
    Lorsch J.R., Szostak J.W., Nature 371 (1994), 31, and
    oligoribonucleotide linkage in Bartel D.P., Szostak J.W., Science 261
    (1993), 1411), and the same applies, as far as I know, to all other in
    vitro ribozyme selection experiments done to date.

    Thus, on both counts, random-path mutagenization to generate a
    previously non-existing activity and natural vs. intelligent selection,
    in vitro ribozyme selection experiments are NOT valid models of the
    crucial steps in darwinian evolution, and the artificial ribozyme
    figures of 10^(-16) or 10^(-13) are irrelevant. The apocryphal joke
    about a horse's teeth is therefore quite inappropriate. We do NOT
    dispose af ANY experimental or observational data about these critical
    steps which would indicate whether macroevolution by natural means alone
    is plausible or not - even quite apart from the origin of life itself.

    Peter Rüst

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