Tuesday, January 4, 2011

Protein Evolution: A Problem That Defies Description

Charles Darwin’s theory of evolution is scientifically unlikely. The idea that all of biology just happened to arise spontaneously over long time periods (yes, that is what the theory of evolution says) is not motivated by the scientific evidence. This can be seen at all levels of biology including, more prominently in recent years, at the molecular level. A good example of this is the scientific evidence on proteins, and what it says about evolution.

It is not that the scientific evidence reveals proteins to be particularly unlikely on evolution. Proteins are not known to be any less likely to have evolved than, say, DNA repair mechanisms, cellular signal transduction, the electron transport chain, neurons, cardiovascular systems, mice or blue whales. But proteins are a bit more amenable to analysis. As mysterious and difficult as proteins are, molecular biology can at least provide some data on their supposed evolution. In the digital molecular world experiments can show how profoundly evolutionary expectations have failed, and how much more faith required to continue with the theory.

One way to understand how unlikely is protein evolution is in their sensitivity to change. Proteins generally do not tolerate much change to their design. Their designs can vary, but not much. In the vast universe of all possible protein designs, they are not vast oceans but more like the tiny holes in a golf course. This evidence indicates the evolutionary process is unlikely to find them.

Another way to understand protein evolution is to start at the beginning rather than the end. That is, rather than analyzing nature’s proteins, one can start with a non functional, random chain of amino acids to see how easily it can migrate toward functional proteins via evolution’s processes of natural selection or drift. These experiments confirm that the evolution of a protein is scientifically unlikely.

Such experiments reveal what seemed rather obvious from biochemistry: evolutionary schemes are not likely to find the highly complex protein designs we find in nature. The results of such experiments fall short of anything close to the real thing. The resulting sequences of amino acids look nothing like what we find in nature, and the resulting functions are orders of magnitude short of what real proteins do.

In fact, such experiments typically need all kind of advantages to show much progress. For instance, some experiments only attempt to evolve a part of a protein, while the rest of the protein is already at nature’s design at the beginning of the experiment. And some experiments apply artificial selection on low levels of trivial functions which otherwise would not improve fitness at the organismal level.

But even with these advantages the results demonstrate the failure of evolutionary expectations. Unfortunately, evolutionists are less than forthright in their representation of what science is telling us. For example, here is how one journal paper reported its results:

By extrapolation, we estimated that adaptive walking requires a library size of 10^70 [a one followed by 70 zeros] with 35 substitutions to reach comparable fitness. Such a huge search is impractical and implies that evolution of the wild-type phage must have involved not only random substitutions but also other mechanisms, such as homologous recombination.

Here the evolutionists must admit the obvious, that the envisioned protein evolution via gradual changes and natural selection does not work. In fact it is ridiculously unrealistic. But they then deny the gravity of the problem. With nothing but speculation they resolve their astronomical long shot with “other mechanisms” such as homologous recombination.

It is one of the great tragedies of our time that most people lack the scientific training to appreciate the incredible absurdity of evolutionary thought. The suggestion that homologous recombination could resolve this astronomical long shot is the height of absurdity. This is not hyperbole.

What cannot be solved with a library size of 10^70 is not magically going to be resolved with homologous recombination. And this is not to mention that homologous recombination would not have even existed when proteins first evolved. Indeed, an army of specialized proteins is required before homologous recombination is even possible. If homologous recombination was the key to evolving proteins, then aircraft carriers were the key to winning the battle of Trafalgar.

Indeed, it is a difficult task to describe the immense magnitude of this evolutionary folly. Here’s my attempt: It would be like throwing a paper airplane from the top of a skyscraper and explaining that it will make a hole-in-one at a golf course on the other side of town. On second thought, that still does not do the job—the evolutionary folly is far greater than this.

145 comments:

  1. Dr. Hunter you golf course analogy would be appropriate if the golf course was the size of over 1 million galaxies and you had only one hole in the golf course. Moreover the size of the hole in your golf course would be the size of a single sub-atomic particle of a single atom in those +1 million galaxies:

    further note:

    The Law of Physicodynamic Insufficiency - Dr David L. Abel - November 2010
    Excerpt: “If decision-node programming selections are made randomly or by law rather than with purposeful intent, no non-trivial (sophisticated) function will spontan...eously arise.”,,, After ten years of continual republication of the null hypothesis with appeals for falsification, no falsification has been provided. The time has come to extend this null hypothesis into a formal scientific prediction: “No non trivial algorithmic/computational utility will ever arise from chance and/or necessity alone.”
    http://www.scitopics.com/The_Law_of_Physicodynamic_Insufficiency.html

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  2. Povolotskaya & Kondrashov 2010, Nature 465, 922-926.

    Deliberately unformatted link due to rubbish blogger software:

    http://www.nature.com/nature/journal/v465/n7300/abs/nature09105.html

    "We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: ~98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, ~3.5 × 109 yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences."

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  3. Great article, thanks Hunter. I would like to see the problem of protein evolution applied to the evolution of the bacterial flagellum.

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  4. CH -

    "The idea that all of biology just happened to arise spontaneously over long time periods (yes, that is what the theory of evolution says)"

    No it is not what ToE says.

    True there is a COMPONENT of random chance to it - random mutation. But these mutations are then fed through the filter of natural selection with only beneficial ones accumulating. And it is only due to this non-random component that allows evolution to take place. The filter of natural selection acts like a ratchet, only allowing the gene pool of a species to move in one direction - towards greater fitness.

    If you put a population of randomly-mutating organism into an environment and watched how they progressed, their evolution would not just drift in any old direction - it would drift only towards greater fitness, ie, adaptedness to their surroundings.

    Okay the mutations upon which natural selection acts ARE random - they are not geared towards increasing fitness. 'Good' mutations are not more likely than 'bad' ones. But this is not sufficient to claim the ToE is down to random chance, indeed it is the very process which follows - the random mutations being filtered through natural selection; chaos giving way to order - that is the central component to ToE.

    Saying ToE states 'all of life happened to arise spontaneously' is extremely misleading and misses out the most vital component - the fixed and non-random filter of natural selection.

    But then that wouldn't fit your strawman, would it?

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  5. Cornelius Hunter: evolutionary schemes are not likely to find the highly complex protein designs we find in nature

    A random string of equal length is no less complex than the wild string. "Adaptive" would be the appropriate word here.


    Cornelius HunterHere the evolutionists must admit the obvious, that the envisioned protein evolution via gradual changes and natural selection does not work. In fact it is ridiculously unrealistic. But they then deny the gravity of the problem. With nothing but speculation they resolve their astronomical long shot with “other mechanisms” such as homologous recombination.

    Recombination is an important part of the evolutionary process. And a basic one, part of ye olde "modern synthesis" along with mutation and selection.

    Cornelius HunterWhat cannot be solved with a library size of 10^70 is not magically going to be resolved with homologous recombination.

    The largest library size used in this experiment was 10^6, not 10^70. Homologous recombination is not magic. Magic is sleight of hand, distraction, and mirage used to create false appearance; homologous recombination appears to be a concrete part of the natural world.

    Cornelius HunterIndeed, an army of specialized proteins is required before homologous recombination is even possible. If homologous recombination was the key to evolving proteins, then aircraft carriers were the key to winning the battle of Trafalgar.

    The first tetrapods to walk the land in the Devonian had clumsy locomotion, and a similar evolutionary attempt today wouldn't stand a chance at producing the success that was achieved the first time around. Fitness landscapes are more forgiving in a world lacking evolved antagonists. Static fitness landscapes over billions of years is an implicit assumption in your calculus.

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  6. Experimental Rugged Fitness Landscape in Protein Sequence Space
    Excerpt: In practice, the maximum library size that can be prepared is about 10^13 [28], [29]. Even with a huge library size, adaptive walking could increase the fitness, , up to only 0.55.

    The question remains regarding how large a population is required to reach the fitness of the wild-type phage. The relative fitness of the wild-type phage, or rather the native D2 domain, is almost equivalent to the global peak of the fitness landscape. By extrapolation, we estimated that adaptive walking requires a library size of 10^70 with 35 substitutions to reach comparable fitness. Such a huge search is impractical,,,
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000096#pone-0000096-g001


    The Case Against a Darwinian Origin of Protein Folds - Douglas Axe - 2010
    Excerpt Pg. 11: "Based on analysis of the genomes of 447 bacterial species, the projected number of different domain structures per species averages 991. Comparing this to the number of pathways by which metabolic processes are carried out, which is around 263 for E. coli, provides a rough figure of three or four new domain folds being needed, on average, for every new metabolic pathway. In order to accomplish this successfully, an evolutionary search would need to be capable of locating sequences that amount to anything from one in 10^159 to one in 10^308 possibilities, something the neo-Darwinian model falls short of by a very wide margin."
    http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2010.1

    The Case Against a Darwinian Origin of Protein Folds - Douglas Axe, Jay Richards - audio
    http://intelligentdesign.podomatic.com/player/web/2010-05-03T11_09_03-07_00

    The following site offers a short summary of the 'Darwinian shortcuts' that failed to overcome Axe's finding for the rarity of protein folds:

    Shortcuts to new protein folds - October 2010
    Excerpt: Axe concludes that all of these putative shortcuts are dead ends. The Darwinian search mechanism is not capable of finding new protein folds by random sampling and all the shortcuts to new folds are dead ends.
    http://idintheuk.blogspot.com/2010/10/shortcuts-to-new-protein-folds.html

    Here is a fairly good defense of the rarity of protein folds, from a blogger called gpuccio, from the best Darwinian objections that could be mustered against it:
    http://www.uncommondescent.com/darwinism/media-mum-about-deranged-darwinist-gunman/#comment-363452

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  7. Talk about being hoisted by your own petard. Here is another excerpt from Hayashi et al. (the PLoS paper linked by Cornelius):

    The landscape structure has a number of implications for initial functional evolution of proteins and for molecular evolutionary engineering. First, the smooth surface of the mountainous structure from the foot to at least a relative fitness of 0.4 means that it is possible for most random or primordial sequences to evolve with relative ease up to the middle region of the fitness landscape by adaptive walking with only single substitutions. In fact, in addition to infectivity, we have succeeded in evolving esterase activity from ten arbitrarily chosen initial random sequences [17]. Thus, the primordial functional evolution of proteins may have proceeded from a population with only a small degree of sequence diversity.

    So this work shows that it is possible to get from a random protein to a functional one through random substitutions and natural selection. The fitness landscape is smooth at the bottom, contrary to what you've been saying.

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  8. With nothing but speculation they resolve their astronomical long shot with “other mechanisms” such as homologous recombination.

    Speculation? Really? Then why oh why have experiments that include recombination shown such amazing power at accelerating the process in what gave birth to the field of directed evolution? Was recombination speculative/imagined? Does recombination not happen in nature?

    Misguided religion drives your pseudoscience, and it matters.

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  9. This comment has been removed by the author.

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  10. I sometimes wonder if this is really a parody site, and Cornelius only posts his silly strawman arguments and 'own goal' data like this paper just to show how idiotic Creationists can be.

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  11. Ritchie said, "True there is a COMPONENT of random chance to it - random mutation. But these mutations are then fed through the filter of natural selection with only beneficial ones accumulating. "

    Question - what if several mutations are required before any benefit can be selected for?

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  12. Neal -

    "what if several mutations are required before any benefit can be selected for?"

    I might have mis-spoke by implying that only beneficial mutations make it through the filter of natural selection. The more accurate way of putting it is that deleterious ones are weeded out. The difference, of course, is neutral mutations - mutations which have no expressed effect on the organism.

    Neutral mutations may or may not occur in the gene pool of a population of organisms. Since there is no particular force promoting their distribution, nor any force promoting their elimination, it is largely a matter of chance whether such neutral mutations spread.

    An example is Lenski's E.Coli bacteria study. I'm doing this from memory, so forgive me if I'm wrong here, but I'm pretty sure the ability one strain developed of digesting citrate was actually the convergence of two (each unlikely) mutations.

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  13. "The filter of natural selection acts like a ratchet, only allowing the gene pool of a species to move in one direction - towards greater fitness."
    This is the fallacy of reification. NS is not a thing, or a mind. It doesn't 'act' or 'allow.'

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  14. In the E coli example two mutations had to occur for it to be able to digest citrate. One of them was useless without the other. The thing was that one of them accumulated in one of the lines of Bacteria before the second had any chance of giving any benefit. Once the first was prevalent enough the second had a chance. The authors were able to trace the first's accumulation to its point of origin. It was neither beneficial, nor deleterious, but its accumulation by random processes allowed for the second to have the right background to make a difference.

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  15. Ritchie: The filter of natural selection acts like a ratchet, only allowing the gene pool of a species to move in one direction - towards greater fitness.

    joel lay: This is the fallacy of reification. NS is not a thing, or a mind. It doesn't 'act' or 'allow.'

    A fish net acts as a sieve, only allowing small fish through, while catching big fish.

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  16. joel -

    "This is the fallacy of reification. NS is not a thing, or a mind. It doesn't 'act' or 'allow.'"

    Natural selection is a process. It does not have to have a mind or 'act' any more than gravity needs a mind to be a force of attraction.

    Would you prefer it if I said: 'Natural selection ensures evolution progresses in only one direction - towards greater fitness'? Does that phrasing offend?

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  17. The OP is a fallacy of fallacies, among them one of incredulity, and, besides its obvious quote-mining techniques, attempts to make a fuss out of lack of properly looking into the question of how proteins evolve.

    The fallacy starts by attempting to question something we can witness to happen, by asking for detailed explanations almost at the atomic level.

    It is like denying that we can obtain breeds of dogs that can smell better than any wolves, hear better, hunt rabbits better, find delicacies better, herd better, and such, because we don't know how exactly that works at the genetic/protein level. It does not matter if we have those details or not, it is a fact that these characters can be improved and become part of the heritage of a line of dogs. Of course, the question as to how these characteristics got improved at such level is very interesting, but finding this question difficult to answer does not mean that breeding did not happen.

    Of course that is compounded with the biased and tricky presentation (like the quote-mining), compounded with the wrong metaphorical examples, all used just to make the problem appear to be harder than it is. But this "problem for evolution" is not a problem for evolution, but a problem for the scientist to find a proper understanding of the process. But understanding the process does not start by making false claims, such as the obviously wrong claim that only a few of all possible amino-acid sequences would comply with such a structure or activity. The literature and most basic knowledge of protein structure and function quickly prove that assumption to be ridiculously false. But Cornelius knows this very well. Example: Will you deny Cornelius that protein families are composed of very dissimilar sequences? That the amount of sequences compatible with a given family makes it hard to find all its members based on overall similarity alone?

    Many other lines of evidence prove that Cornelius is tendentiously presenting (misrepresenting) the question of protein evolution (and evolution itself), but again, being lost in the details does not mean that evolution is not possible. It just means that you got lost in the details. The wrong details for that matter.

    Misguided religion drives your pseudoscience, and it matters.

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  18. Ritchie said, "An example is Lenski's E.Coli bacteria study. I'm doing this from memory, so forgive me if I'm wrong here, but I'm pretty sure the ability one strain developed of digesting citrate was actually the convergence of two (each unlikely) mutations."

    And so we see the edge of evolution here. What if three or four or ten or more of these neutral mutations are necessary before any benefit is gained? Natural selection doesn't even have a chance of working until you get a benefit. Doesn't the possibility of neutral mutations accumulating correctly towards a net benefit potential become EXPONENTIALLY larger as a mutation is added? It took tens of thousands of generations of adaptive bacteria to yield something like a two mutation benefit. Yet we are to believe that a land animal lineage evolved into a full blown whale in less than a million generations?

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  19. Neal Tedford: And so we see the edge of evolution here.

    Several other adaptive changes occurred during the same period of time.

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  20. oleg:

    ===
    Talk about being hoisted by your own petard.
    ===

    The paper is yet another support for what I have earlier explained. More below ...


    ===
    Here is another excerpt from Hayashi et al. (the PLoS paper linked by Cornelius):

    The landscape structure has a number of implications for initial functional evolution of proteins and for molecular evolutionary engineering. First, the smooth surface of the mountainous structure from the foot to at least a relative fitness of 0.4 means that it is possible for most random or primordial sequences to evolve with relative ease up to the middle region of the fitness landscape by adaptive walking with only single substitutions. In fact, in addition to infectivity, we have succeeded in evolving esterase activity from ten arbitrarily chosen initial random sequences [17]. Thus, the primordial functional evolution of proteins may have proceeded from a population with only a small degree of sequence diversity.

    So this work shows that it is possible to get from a random protein to a functional one through random substitutions and natural selection. The fitness landscape is smooth at the bottom, contrary to what you've been saying.
    ===

    No, once again, this is not contrary to what I've been saying, which is that there is no scientific evidence that in the universe of sequence space there generally are bridges of functional intermediates, or smooth landscapes, leading to the native proteins. In this case, their experiment led nowhere close to the native domain, either in sequence space (no detectable similarity beyond random) or function (orders of magnitude lower).

    Furthermore, they did not begin with a random protein as you suggest -- they randomized a particular domain within a protein, with the remainder of the protein, and the other proteins it works with, already at their native sequence at the beginning of the experiment.

    This paper is yet another confirmation of what I explained earlier. The randomly driven change they were able to demonstrate got them nowhere towards the native sequence, and led to a stagnation in the search. They rightly concluded that it isn't a workable approach.

    Make sense now?

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  21. Neal -

    "What if three or four or ten or more of these neutral mutations are necessary before any benefit is gained?"

    Then the chances of the same mutations occuring in the same individual become increasingly less likely. Do you have a particular example in mind, or are you just talking hypothetically? Because, to my mind, a feature that relies on ten entirely neutral mutations is rather a complex one. And can these ten mutations really all be beneficially neutral - even in combination? Will nine really simply not suffice? This sounds rather odd.

    "It took tens of thousands of generations of adaptive bacteria to yield something like a two mutation benefit. Yet we are to believe that a land animal lineage evolved into a full blown whale in less than a million generations?"

    The cases are hardly comparable. It took tens of thousands of generations for the E.Coli to yield a combination of two neutral mutations. Essentially they were just playing a waiting game until these mutatuions came along. That is not the case for whales. Creatures do not just sit around waiting for mutations until they can enter new environments. They manage as best they can in new environments - and those that are best at it will simply be more likely to survive. Ambulocetus did not just passively sit on the banks of rivers, gazing longingly into the waters thinking: 'Maybe one day...' and then finally a child born with flippers! Hurrah! Into the water he dives!

    If all the top predators in the oceans disappeared and wild dogs started making a living on the edges of rivers, some would already be better suited to a life in water than others. There is already variation. There is no sitting around waiting for necessary mutations. Natural selection would simply work on the variation that already exists in the gene pool.

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  22. Cornelius:

    "No, once again, this is not contrary to what I've been saying, which is that there is no scientific evidence that in the universe of sequence space there generally are bridges of functional intermediates, or smooth landscapes, leading to the native proteins."

    There is ample scientific evidence that many very different proteins can perform the same function (e.g., Omelchenko et al. 2010, Biology Direct 5:31). Therefore, it is unlikely that any experiment starting with a random polypeptide will end up near the "native" protein, since there are many others that can do the same. The important point is that proteins performing the same function as the "native" protein can evolve experimentally from (partially) randomized ancestral proteins. Therefore, there are plenty of smooth trajectories to functional proteins, which do not function at "orders of magnitude" lower performance (is 0.4 orders of magnitude lower than 1?)

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  23. Cornelius wrote: This paper is yet another confirmation of what I explained earlier. The randomly driven change they were able to demonstrate got them nowhere towards the native sequence, and led to a stagnation in the search. They rightly concluded that it isn't a workable approach.

    We have two different things here. (1) Getting to a functioning protein starting from a random one. (2) Getting to the native protein. The work done by these authors shows that incremental random changes plus feedback are enough to accomplish the first goal but not enough to accomplish the second.

    That's fine as far as I am concerned. Evolution is not supposed to yield the same result twice precisely because the fitness function has local maxima and an evolutionary process can easily get stuck near a local maximum. Different starting points lead you to different local maxima. The same happens in Monte Carlo simulations of various frustrated systems (e.g., glasses).

    The authors speculated about what sort of steps might help a protein make larger moves in the configuration space. A nonlocal move is required to overcome the attraction of a local maximum and get to the basin of attraction of another, possibly higher one. (That sort of thing is, again, well known in statistical physics.) Homologous recombination is one such process that is known to exist.

    But getting to the best possible protein is really icing on the cake. The researchers managed to obtain functional proteins by starting from nonfunctional ones and using the simplest procedure consistent with theory of evolution: small random changes plus feedback. It worked in the sense that they got functional proteins.

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  24. troy:

    ===
    is 0.4 orders of magnitude lower than 1?
    ===

    Yes, the 0.4 you refer to is their fitness measure. They use the log of the function as their fitness measure.

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  25. The authors define fitness W as the logarithm of infectivity. The observed increase of infectivity by a factor of 1.7x10^4 (compared to the randomized protein) corresponds to a fitness increase by ln(1.7x10^4) = 9.7.

    Their W-tilde is a relative fitness obtained by normalizing W to the fitness of the native protein. The newly selected protein had relative fitness of 0.52. That means that the native protein had W = 18.7 and infectivity of exp(W) = 1.4x10^8, or 8,000 times higher.

    So, on the logarithmic scale, the newly found protein was half way between a random one and the native protein.

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  26. And this is not to mention that homologous recombination would not have even existed when proteins first evolved. Indeed, an army of specialized proteins is required before homologous recombination is even possible.

    For homologous recombination to occur in a primitive form of life all you need is a partially replicated strand to pair with a strand other than, but homologous to, the one it was replicating. Also, I have not seen any battery of proteins being required for the accidents that homologously recombine strands of DNA during a PCR reaction. Have you?

    Misguided religion drives your pseudoscience, and it matters.

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  27. Neal,

    And so we see the edge of evolution here.

    I would say the edge of evolution for this particular evolutionary "problem."

    What if three or four or ten or more of these neutral mutations are necessary before any benefit is gained?

    What if under a different background all it takes in one or two mutations instead?

    It took tens of thousands of generations of adaptive bacteria to yield something like a two mutation benefit.

    Actually an unexpected benefit. But also think how unrealistic it is to expect this to be any quicker if we are denied, by the experimental setting, enough variety of bacteria within each flask for taking different routes towards different solutions. We can only expect limited results within experimental settings where we reduce as many variables as possible so as to learn what one process or another can bring to evolution. Yet it does move! (Eppur si muove).

    Yet we are to believe that a land animal lineage evolved into a full blown whale in less than a million generations?

    We are not expected to believe it. This, again, is not religion. If the evidence shows so, then it did happen. Investigating what was required for it to happen is a good idea, but there is no point in denying what the evidence shows. Right?

    Would you deny that we have gotten such a variety of dogs by breeding because we don't know the underlying mutations behind them?

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  28. Neal TedfordYet we are to believe that a land animal lineage evolved into a full blown whale in less than a million generations?

    After the appearance of (mostly) terrestrial Pakicetus, there's twenty million years before we get to anything you might generously call "full blown whales", early forerunners of the surviving baleen and toothed whale lines. That's probably closer to 5 to 10 million generations.

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  29. oleg:

    ===
    We have two different things here. (1) Getting to a functioning protein starting from a random one. (2) Getting to the native protein. The work done by these authors shows that incremental random changes plus feedback are enough to accomplish the first goal but not enough to accomplish the second.
    ===

    It was not "functioning" by normal standards. It was orders of magnitude from normal function when the search stagnated. Nor was it a protein. Most of the protein, and the other proteins it worked with, were already at their native sequence. They merely randomized one domain.


    ===
    That's fine as far as I am concerned. Evolution is not supposed to yield the same result twice precisely because the fitness function has local maxima and an evolutionary process can easily get stuck near a local maximum. Different starting points lead you to different local maxima. The same happens in Monte Carlo simulations of various frustrated systems (e.g., glasses).
    ===

    Right.


    ===
    The authors speculated about what sort of steps might help a protein make larger moves in the configuration space. A nonlocal move is required
    ===

    Right, and there is no scientific evidence that the first proteins could have been evolved by such nonlocal moves. For instance, the homologous recombination itself requires proteins.


    ===
    to overcome the attraction of a local maximum and get to the basin of attraction of another, possibly higher one. (That sort of thing is, again, well known in statistical physics.) Homologous recombination is one such process that is known to exist.
    ===

    Picture a huge landscape that is rugged with many minor ups and downs, but no significant upward slopes. Then, extremely rarely you have a spike shooting straight up. These spikes are the fully functional proteins. You cannot find them easily. Non local moves do not provide any magical way to find the spikes. This is what the scientific evidence is indicating the protein function looks like, in the protein amino acid sequence space.


    ===
    But getting to the best possible protein is really icing on the cake.
    ===

    They were nowhere even close to best possible.


    ===
    The researchers managed to obtain functional proteins
    ===

    Again, it was a domain, not the full protein. And calling them "functional" is a huge exaggeration. You can remove chunks of protein machines and still have them work. In this case, the researchers randomized a single domain, and with some tweaks were able to avoid the machine being completely disabled. The morphed domains likely do not even fold. (I didn't see mention of this in the paper, but that is the case in other such experiments). It would be a huge mischaracterization of these results to say they evolved new, functional, proteins, or even if not that, to say that they demonstrated the feasibility of evolving new, functional, proteins.

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  30. Negative Entropy: "What if under a different background all it takes in one or two mutations instead?"

    Then you would be talking only about proteins that were different by one or two mutations and these are found more quickly in experiments.

    "Actually an unexpected benefit."

    No, it was a known benefit that was knocked out.

    "But also think how unrealistic it is to expect this to be any quicker if we are denied, by the experimental setting, enough variety of bacteria within each flask for taking different routes towards different solutions."

    You know that bacteria reproduce asexually right? Every bacteria is it's own route. The rate at which diversification is created is precisely what is being studied. Perhaps you're thinking of speciation events that apply to sexually reproducing species?

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  31. Cornelius wrote: They were nowhere even close to best possible.

    They don't need to be best. Just better than others in order to get a reproductive advantage. Which is precisely what happened.

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  32. John: You know that bacteria reproduce asexually right? Every bacteria is it's own route. The rate at which diversification is created is precisely what is being studied. Perhaps you're thinking of speciation events that apply to sexually reproducing species?

    Bacteria reproduce without sex, but also have "sex" (genetic exchange) outside of reproduction through conjugation and transduction. Bacterial evolution would indeed be much more limited if it were confined to mutation, selection, drift without these processes. By disallowing contact with a diverse bacterial community, they are indeed modelling a poor sister of the full process of bacterial evolution.

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  33. Hunter:

    Right, and there is no scientific evidence that the first proteins could have been evolved by such nonlocal moves. For instance, the homologous recombination itself requires proteins.

    Eggs require chickens. There is no scientific evidence that the first eggs could have evolved without chickens.

    In any case, the quoted paper illustrates the power of selection within a restricted compass, and does not address the origin of proteins from the primordial soup.

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  34. Oleg:

    "They don't need to be best. Just better than others in order to get a reproductive advantage. Which is precisely what happened."

    anaxyrus:

    "Bacteria reproduce without sex, but also have "sex" (genetic exchange) outside of reproduction through conjugation and transduction. Bacterial evolution would indeed be much more limited if it were confined to mutation, selection, drift without these processes. By disallowing contact with a diverse bacterial community, they are indeed modelling a poor sister of the full process of bacterial evolution."

    Troy:

    "There is ample scientific evidence that many very different proteins can perform the same function"
    ===

    Everything just happened to turn out optimal. Don't ask us how, how dare you. Just believe!!!

    YAWN

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  35. PEDANT:

    "In any case, the quoted paper illustrates the power of selection within a restricted compass, and does not address the origin of proteins from the primordial soup."
    ===

    Of course not, origins are a taboo and sacrilege of all that's Darwinian. And that the problem. Never talk straight biology and how originally nothing more than blind unintelligent forces of physics and chemicals got it all started. No, instead let's hijack perfectly common sense functionality and cloak it with the gloss of evolutionary dogma and argue from there.

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  36. Eocene -

    "Everything just happened to turn out optimal. Don't ask us how, how dare you. Just believe!!!"

    A perverse retort. Partly because no-one is putting forward the argument that everything turned out optimally. In fact the quotes you cited say quite the opposite. But mostly because no-one is outraged that anyone else has the audacity to question/challenge them.

    In short, a swing and a miss.

    " origins are a taboo and sacrilege of all that's Darwinian."

    Either that or the origin of life is not part of the theory of evolution!

    "Never talk straight biology and how originally nothing more than blind unintelligent forces of physics and chemicals got it all started."

    That would be abiogenesis, and scientists are working on it.

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  37. Cornelius Hunter : It was not "functioning" by normal standards.

    All proteins (even the one with a fully randomized domain) had positive fitness and infectivity. All were at least weakly functional. Selection produced a great upswing in functionality over the very short run of the experiment. The end result indeed had far lower function than the wild version.

    It was orders of magnitude from normal function when the search stagnated. Nor was it a protein. Most of the protein, and the other proteins it worked with, were already at their native sequence. They merely randomized one domain.

    One of three domains was randomized. That's a pretty drastic change in the protein, and it sure kicked the stuffing out of infectivity. Considering the drastic change in the D2 domain, the protein might well function better with accommodating changes to the other domains. As the protein naturally evolved over history, the three domains were evolving together. Evolution does not work through saltational changes in one-third of a protein at a time. They are not trying to recreate the evolution of the protein in question here; they are instead investigating the fitness landscape.

    Cornelius Hunter: Right, and there is no scientific evidence that the first proteins could have been evolved by such nonlocal moves. For instance, the homologous recombination itself requires proteins.

    The first proteins arose in a world without the antagonistic ecology we are used to. Fitness landscapes would not have been this rugged. Proteins we would consider highly dysfunctional today could have worked just fine in that world. Proteins and fitness landscapes evolved together over time. This particular landscape under study would be expected to be highly rugged as it is a product of a coevolutionary arms race between increasingly infective viruses and increasingly resistant bacteria over time.

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  38. Cornelius Hunter: Picture a huge landscape that is rugged with many minor ups and downs, but no significant upward slopes. Then, extremely rarely you have a spike shooting straight up. These spikes are the fully functional proteins. You cannot find them easily. Non local moves do not provide any magical way to find the spikes. This is what the scientific evidence is indicating the protein function looks like, in the protein amino acid sequence space.

    Not only do organisms coevolve in the community, but proteins coevolve together within the lineage of the organism over time. Natural selection yields proteins that work together as a team. Some slight changes in a single protein are well tolerated. Further change may require (or even be spurred by) compensatory change in other proteins. Fitness landscapes evolve over time; single peaks can split into two peaks as orthologs diverge.

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  39. Ritchie:

    "A perverse retort. Partly because no-one is putting forward the argument that everything turned out optimally. In fact the quotes you cited say quite the opposite. But mostly because no-one is outraged that anyone else has the audacity to question/challenge them."
    ===

    Really, so the whale fable you invented on the fly is true ???
    ---

    Ritchie:

    "Either that or the origin of life is not part of the theory of evolution!"
    ===

    Ah yes, that's comforting for the faithful to know and believe in.
    ---

    Ritchie:

    "That would be abiogenesis, . . . "
    ===

    No that's still evolution, but it's just the inert inanimate part of the same No-God/Intelligence allowed ideological dogma where unguidance and undirectedness reigns supreme.
    ---

    Ritchie:

    " . . . and scientists are working on it."
    ===

    If we can just get our multi-million $$$ Lab experimental device up and running with all the collective genius of the cream of the crop evolutionary scientists to just create life in a test tube, then we'll prove once and for all that life never required intelligence in the beginning.

    Or the Bill Bigge scenario: If I can just program my computer to get digital organisms to evolve by natural selection, then I will have proven that no intelligence was necessary at the beginning.

    YAWN!!!

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  40. anaxyrus:

    "The first proteins arose in a world without the antagonistic ecology we are used to. Fitness landscapes would not have been this rugged. Proteins we would consider highly dysfunctional today could have worked just fine in that world."
    ===

    Interestingly enough as more and more functional ecosystem(type doesn't really matter) componants of the natural world(on a complete global scale) today come under attack, fail and in many cases disappear, the environment becomes more and more chaotic and inhospitable even for the existing life that already exists in these. Hardly a favourable environment for intelligence driven life, let alone things supposedly unduided or undirected. However, never underestimate the value of a feels good story and a power in numbers strategy when it comes to informational wars in any evos/vrs/creos blog/forum comments venues.

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  41. Eocene -

    "Really, so the whale fable you invented on the fly is true ???"

    1) Another response totally disjointed from the preceeding quote.
    2) I did not invent any fable on the fly.
    3) The theory that whales evolved from land-living mammals is indeed well-established and exceedingly well evidenced. It is indeed - as far as we can tell, though we're pretty certain on this matter - true.

    "Ah yes, that's comforting for the faithful to know and believe in."

    Your derision counts for nothing.

    "No that's still evolution, but it's just the inert inanimate part of the same No-God/Intelligence allowed ideological dogma where unguidance and undirectedness reigns supreme."

    Wrong again. Abiogenesis and evolution are seperate theories. Related, granted, but seperate. Please make some effort to understand.

    "If we can just get our multi-million $$$ Lab experimental device up and running with all the collective genius of the cream of the crop evolutionary scientists to just create life in a test tube, then we'll prove once and for all that life never required intelligence in the beginning."

    You need a lot of people and effort to recreate environmental conditions of the first life, and to make sure experiments are properly controlled.

    Do not assume that professional scientists whose job it is to know such things would be dumb enough to PURPOSEFULLY ENGINEER life and then hold it up as evidence of such things happening spontaneously.

    That is a strawman-in-advance. No-one is dumb enough to do that. Credit them with just a sliver of intelligence!

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  42. John,

    You know that bacteria reproduce asexually right?

    Sure do. I work with them.

    Every bacteria is it's own route.

    Not quite. There are viruses called phage that can jump from one to another bacterium and carry genes among them, there is the possibility for taking DNA from their environments, there are horizontally-jumping elements, such as transposons and plasmids, there are micro-environments where lineages can diverge independently, yet lineages backgrounds and proximities can be compatible enough for successful recombinations and insertions had any of these elements transfer genes between them. Hardly can any bacteria be its own route.

    The rate at which diversification is created is precisely what is being studied.

    Under very specific conditions.

    Perhaps you're thinking of speciation events that apply to sexually reproducing species?

    Not at all.

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  43. Ritchie:

    "The theory that whales evolved from land-living mammals is indeed well-established and exceedingly well evidenced. It is indeed - as far as we can tell, though we're pretty certain on this matter - true."
    ===

    LOL, all ya gotta do is believe Ritchie.
    ---

    Ritchie:

    "Wrong again. Abiogenesis and evolution are seperate theories. Related, granted, but seperate. Please make some effort to understand."
    ===

    Oh I understand TOTALLY the NECESSITY to definition shell game it and separate both to relieve one of any responsibility of dealing with blind forces of physics and chemcials and moving on the imagined directed world of Evolutionism. As Pedant said, western(secular progressive version) civilization(ideology) is at stake. And ultimately, isn't that what this whole mess is all about anyway ???
    ---

    Ritchie:

    "You need a lot of people and effort to recreate environmental conditions of the first life, and to make sure experiments are properly controlled."
    ===

    I believe the official mandate of evolution being FACT takes care of the controlled part, don't you Ritchie ???
    ---

    Ritchie:

    "Do not assume that professional scientists whose job it is to know such things would be dumb enough to PURPOSEFULLY ENGINEER life and then hold it up as evidence of such things happening spontaneously."
    ===

    What's to assume ??? The madated ideology gives it all the excuse/purpose necessary. One thing is clear, the time wasted in dogma proofing is valuable time taken away from viable solutions to reversing the present day global ruination which many of these geniuses you hold so dear caused us all in the first place.

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  44. Eocene -

    "LOL, all ya gotta do is believe Ritchie."

    That, or turn to the massive amounts of corroborative data. Not that you will, of course.

    "Oh I understand TOTALLY the NECESSITY to definition shell game it and separate both to relieve one of any responsibility of dealing with blind forces of physics and chemcials and moving on the imagined directed world of Evolutionism."

    It's not done out of necessity. From the very beginning ToE was very clear about what the mechanism of natural selection does and does not explain - the development and diversification of life on Earth, but not its origin.

    "As Pedant said, western(secular progressive version) civilization(ideology) is at stake. And ultimately, isn't that what this whole mess is all about anyway ???"

    Indirectly. The stakes are the scientific literacy of the western world, which is being flooded with nonsense from the ID/Creationist crowds. Notice they win support chiefly among the lay public, whose scientific knowledge is infamously lamentably poor. The people who never seem convinced by ID/Creationism are the scientists themselves - ie, the people who actually know a thing or two about science. I wonder why that is...

    "I believe the official mandate of evolution being FACT takes care of the controlled part, don't you Ritchie ???"

    No. For one thing, this is not evolution.

    Seriously, do you even know what a controlled experiment IS?

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  45. (cont)

    "What's to assume ??? The madated ideology gives it all the excuse/purpose necessary."

    The fact that scientific research is being done in this field at all totally belies your accusations. If this was just mandated ideology, no-one would be putting it to the test, would they, brainiac?

    Not that I expect you to be familiar with the concept of testing your ideas...

    "One thing is clear, the time wasted in dogma proofing is valuable time taken away from viable solutions to reversing the present day global ruination which many of these geniuses you hold so dear caused us all in the first place."

    That may or may not be true. But absolutely nothing about the environmental crises we face today suggest ToE is in error. In fact, it is the Christian right (who are champions of ID) who remain the most ardent climate-change sceptics, wasting precious time and insisting the data are muddled, unclear and require no immediate action. After all, don't you know: 'God will provide'?

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  46. Eocene,

    Can you demonstrate that people working in either evolution or in abiogenesis caused the global warming problem? Otherwise it would be wise for you to stop this needless accusation.

    Oh I understand TOTALLY the NECESSITY to definition shell game

    What is there to shell? Evolution has very strong support. The whale history is one of those beautifully documented even at the level of fossil evidence which creationists are so eager to close their eyes and ears against. Just do a bit of googling about it and you will see. Abiogenesis, on the other hand, is a tad harder to work on. After all, we have the disadvantage of more than 3.5 billion years erasing evidence and data that we could use.

    it and separate both to relieve one of any responsibility of dealing with blind forces of physics and chemcials and moving on the imagined directed world of Evolutionism.

    What? Both are naturally separated. The evidence for evolution is undeniable (within reason). Creationists blend them to be able to deny both. Why do you think Cornelius did not answer me if there was a thermodynamic difference between reproducing a selected sub-population and reproducing an established population?

    As Pedant said, western(secular progressive version) civilization(ideology) is at stake. And ultimately, isn't that what this whole mess is all about anyway ???

    What? The "whole mess" is performed by misinformed people, not by scientists. There is no mess whatsoever on the scientific side. Ignorance and misinformation among creationists don't make evolution any less strong. Have you tried to truly understand the science Eocene? If your "information" comes from the likes of our blog host, I am not surprised of your attitude. But if you wanted to truly know you have no excuses. Just go to the proper places, and make the effort to learn. I can't force knowledge into your mind. Learning is a very personal process.

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  47. Anaxyrus:

    A protein has to function well enough to be biologically viable. It isn't enough to just function at all. Did the proteins produced in the experiment function well enough?

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  48. Define "well enough," natschuster.

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  49. Negative Entropy:

    "Can you demonstrate that people working in either evolution or in abiogenesis caused the global warming problem? Otherwise it would be wise for you to stop this needless accusation."
    ===

    What are you talking about ??? I'm talking about time wasted proving and justifying something that is clearly nothing more than a philosophical worldview being pushed off as science. In most of these debates, "SCIENCE" period is almost always promoted by your gang as mankind's only hope and savior and thus far we just don't see that. At this late date we are in dire need of FACTS & SOLUTIONS as opposed to more hypothesizing and theory invention to prop up another religious worldview. Seriously, if they don't quickly get a handle on this downward environmental spiral, this planet physically is in trouble beyond a point of repair. At some point whether it's blind chanced evolution or intelligently designed nature, the mechanisms will break down no matter what the understanding. Keep watching there News Neg-Ent.
    ---

    Negative Entropy:

    "What is there to shell?"
    ===

    The shell game of what and what is not evolution, but then you already knew that. It'll always be made muddled, murky and fuzzy. It's real easy, Abiogenesis/Evolution are one and the same. Always were and always will be. Non-life begets life, non-sense begets sense, non-intelligence begets intelligence.
    ---

    Negative Entropy:

    "Both are naturally separated."
    ---

    Not a chance. You want evolution/natural selection as the wonder maker of directedness and a guided phenomena. Again not a chance. Show first how such wonderful guided functionalities were birthed by nothing more than blind pointless indifference without purpose or intent and then we'll discuss the squabblings going on here with guided molecular machines creating evolutionary wonders. Hijacking and changing the rules halfway through the games doesn't cut it. Trees have roots and foundation or they fall over.
    ---

    Negative Entropy:

    "There is no mess whatsoever on the scientific side."
    ===

    Spoken like a true ideologue!!! Monsanto is a prime example of where science goes terribly wrong. Google a closer look at the Wiki-Leaks exposure of the memos and see where this Science Industrial giant merges in bed with U.S. politics. It's about power and wealth and nothing to do with mankind's benefit and understanding as a whole.

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  50. Eocene said "It's real easy, Abiogenesis/Evolution are one and the same. "

    Yeah guys, get with the program. In that same way, since organisms are made of atoms, atomic theory and evolution are also one and the same. Also, since organisms inhabit spacetime, evolution and relativity are one and the same. And since organisms (as far as we know) live on planets, evolution and planetary formation are one and the same. If there are unresolved areas of any of the fields of study of atomic theory, relativity, or planetary formation, then evolution is false. Duh.

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  51. Eocene said: "Not a chance. You want evolution/natural selection as the wonder maker of directedness and a guided phenomena. Again not a chance. Show first how such wonderful guided functionalities were birthed by nothing more than blind pointless indifference without purpose or intent and then we'll discuss the squabblings going on here with guided molecular machines creating evolutionary wonders."

    A-men. In that same way, don't even think about giving phony-baloney 'explanations' of things like plate tectonics or subduction regions or pole reversals or erosion until you can demonstrate conclusively how planets are formed in the first place.

    And don't give me any of that 'gravity pulling cosmic debris together' nonsense- I want to know the order of every two rocks that smashed together due to this 'unintelligent' force known as gravity.

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  52. Ritchie:

    "No. For one thing, this is not evolution.

    Seriously, do you even know what a controlled experiment IS?"
    ===

    Of course I do, especially since I have run controlled neutral potting media experiments in a closed nursery seedling germination and at the same time experimenting with mycorrhizal innoculations with regards rooting benefits in the media. But these experiments are neutral and have zero to do with either creationism, IDism or evolutionism which require huge bias on all sides. So don't tell me there is no bias control. Lenski is just one that comes to mind. Like Sagan's take on the difference between astronomy and astrology, there's a way of looking at a subject they way it really is or the way we wish them to be. BIAS!!!

    Here's a prime example of bias manipulating what should otherwise be a neutral experiment. The FDA is considering canceling some drug studies because of placebo bias. The question has been who decides what makes up the placebo ??? Let's take diabetic drug experiments. On the BIG-PHARMA side when it comes to diabetic drugs, they decide what goes into the placebo. Some recent findings have found that most all placebos were of the usual sugar pill variety and it doesn't take a Genius to figure out that the drug test patient(Guinea Pig) is going to out perform the sugar pill patient(Guinea Pig) when it comes to Diabetics experiments. The drug will win every time which translates into the results they are looking to obtain all along. $$$$$$$. The evo/Creo debate is no different for either side. $$$$$$$$. On the religious side it shouldn't be, but we both know better.

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  53. continued:

    ...so until you can explain exactly how an undirected, unintelligent force like gravity can cause the formation of planets, don't bother trying to convince us of anything that happens on a planet after its formation.

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  54. I'm not going to write much because of all of the problems I've had trying to post here.

    C. Hunter, in his 1-4-11, 1:41 post, laid out the rather severe problem this work presents. The authors write: "The evolvability of arbitrary chosen
    random sequence suggests that most positions at the bottom of the
    fitness landscape have routes toward higher fitness."

    Here's the problem (and that is why the authors, earlier in the paragraph say that theirs is a 'remarkable finding'): ANY random sequence can begin the climb up Mt. Improbable.

    But....but.....this 'proves' Dawkins correct!!! Not exactly. But what it does point to ('prove' is such a strong word) is that there are no early constraints on a random sequence. Think about this for a second. What Darwinists suppose is that there are hidden natural forces which exclude sequences from forming, and thus LIMITING sequence space. But this is exactly what "doesn't" happen. IOW, the incredible improbabilities calculated for strings of nucleotide bases are, in fact, valid. So, at the 'base' of these landscapes, anything goes. But once the climb begins, and above a certain threshold (approx 55% of target function), huge libraries of functional sequences are needed to continue the journey.

    Bottom line: at the bottom of the fitness landscapes one a.a. is as good as another. That is: NO specificity required. Once above 55% of native function, EXTREME specificity comes into play. This is right out of the ID playbook!

    Another day, another study, another sad day for Darwinism!

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  55. This comment has been removed by the author.

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  56. This comment has been removed by the author.

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  57. lino235: But what it does point to ('prove' is such a strong word) is that there are no early constraints on a random sequence.

    That's right. A rather non-specific sequence can have minimum function. But a 17000x increase in infectivity occurs within just a few generations. New functionally specific information! It's typical for this type of evolutionary process to become stuck on a local maximum. Recombination can allow the process to explore other peaks.

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  58. Zachriel:

    Sorry. But the paper points out that they had a random sequence reach 40% of the native function and it had ZERO sequence compatibility with the native protein.

    What you're failing to take into account is that there is no way that a sequence that produces 40% of function can compete with one that gives 100%. For the sequence to be fully functional, it must be fully specified. This is an improbable event, just as their calculation of a needed 10^70 library to reach higher functionality points out.

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  59. lino235: But the paper points out that they had a random sequence reach 40% of the native function and it had ZERO sequence compatibility with the native protein.

    Yes, 0.4 normalized fitness.

    lino235: What you're failing to take into account is that there is no way that a sequence that produces 40% of function can compete with one that gives 100%.

    It competes successfully with those that have lower fitness. That's how it evolved. In the experiment, which doesn't includes recombination, it reached a local maximum.

    lino235: For the sequence to be fully functional, it must be fully specified.

    The evolved clone is fully functional, just not as potent as the native variant. In any case, they didn't test recombination, which allows the process to move off of local maxima.

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  60. lino235,

    Your scenario does not make sense. At the beginning, the native protein did not exist. Barely functional proteins would compete among themselves and the most successful ones would emerge from this competition.

    Furthermore, you are totally misreading the paper about the need for a larger library. With the library of a modest size, the protein fitness reached 52% of the native one. (The 40% figure is where the landscape becomes rugged.) Increasing the library to 10^70 does not do much to improve on that: by the authors' estimate, the fitness will only bump up another 3% to 55%.

    The authors speculate that an efficient way to move through the rugged landscape is to employ nonlocal moves. (This is exactly how a similar problem is overcome in statistical Monte Carlo simulations.) Homologous recombination is one example of such nonlocal moves.

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  61. Zachriel:

    I have a question for you: in what way, specifically, does recombination help in the journey to higher fitness?

    Oleg:

    What doesn't make sense in my scenario?

    The Darwinist's implicit belief is that nature has a way of overcoming the unimaginable improbabilities presented by sequence permutations of long strings of a.a.s. If this were true, then nature would need to apply some kind of constraint to the sequencing. Where is this evident in this paper? We see, instead, that a sequence with no commonality with the wild-type sequence is able to reach 40% infectivity. Where are the constraints on sequencing?


    The question remains regarding how large a population is
    required to reach the fitness of the wild-type phage. The relative
    fitness of the wild-type phage, or rather the native D2 domain, is
    almost equivalent to the global peak of the fitness landscape. By
    extrapolation, we estimated that adaptive walking requires a library
    size of 1070 with 35 substitutions to reach comparable fitness.

    Have I misread the paper?

    Here's what it says about the library size:

    The question remains regarding how large a population is required to reach the fitness of the wild-type phage. The relative fitness of the wild-type phage, or rather the native D2 domain, is almost equivalent to the global peak of the fitness landscape. By extrapolation, we estimated that adaptive walking requires a library size of 10^70 with 35.

    I would also ask you what, specifically, not in a vague way, is the importance of recombination?

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  62. lino235: I have a question for you: in what way, specifically, does recombination help in the journey to higher fitness?

    The limitation of evolution by only point-mutations is that it tends to get stuck on local maxima. Recombination allows it to move off these maxima. We can show that evolutionary algorithms that include recombination perform quite differently than those that only include point-mutation.

    lino235: If this were true, then nature would need to apply some kind of constraint to the sequencing. Where is this evident in this paper?

    The constraint, in terms of the fitness function, is uphill until it reaches a maximum.

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  63. Eocene wrote:

    No that's still evolution, but it's just the inert inanimate part of the same No-God/Intelligence allowed ideological dogma where unguidance and undirectedness reigns supreme.

    You would be hard pressed to find someone who a good grasp of both science and the theory itself who claimed evolutionary theory who doesn't "allow God". It's a false dilemma. In the same way, evolutionary theory suggests that intentional guidance or direction was not necessary, not that it's "not allowed".

    That's like saying the claim that one can travel from NYC to San Francisco via automobile doesn't optionally allow for the car to have transported by ferry, pulled by a train on a boxcar, etc., during a leg of the journey.

    For example, It's possible that God wanted us to have five fingers on our hands, rather than four, six or some other number eventually formed via the process of evolution. And if God is omnipotent and omniscient, he could have intervened to bring that specific number about in a way which was indistinguishable from a non-directed process. We'd be none the wiser.

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  64. -- Continued --

    As such, what we need is a reason to think God was actually concerned with the exact number of digits on our hands. And since God is supposedly agent, which makes choices based on a number of different factors, we need a reason to assume God actually chose intervene in the case of human beings.

    For example, God could have designed every detail of biological complexity, but decided to keep his involvement hidden by doing so in a way that overwhelmingly suggests it was formed by a natural process.

    We can expand this line of questioning from fingers to the entirety of biological complexity. Why human beings, rather than some other form of life? And from there we can ask, why biological life at all? Since there supposedly exists some non-material realm where other non-material beings exist and are free to obey or disobey God, then why do we need a physical reality at all?

    Of course, theological responses to this line of questioning tends to vary greatly depending on who you ask.

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  65. I wrote:

    For example, God could have designed every detail of biological complexity, but decided to keep his involvement hidden by doing so in a way that overwhelmingly suggests it was formed by a natural process.

    Eocene,

    Would you think science was "wrong" for reaching this conclusion should God choose to use his omnipotence and omniscient powers to overwhelmingly make it appear this was indeed the case?

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  66. lino235,

    Apparently, and correct me if I misunderstood, you think that evolution means that these sequences should start looking like the wild-type sequences (as in having the same amino-acids). If so, you are plainly wrong. All evolution means is that starting with random sequences and subjecting to rounds of selection /variation we will find sequences with improved function. Actually, if I saw them reaching a protein similar in sequence to the wild type I would suspect the experiments. Evolution is possible because there are much more than just one solution to particular problems.

    Of course there are constrains to which sequences will work, but not in what mutations will appear. Any visible bias should be due to the constrain of selection. But such constrain is functional, not necessarily one to guide the sequence to a specific amino-acid order.

    As for recombination, people have performed experiments with point mutations, then found to be able to attain unexpected jumps in performance by adding recombination to them. Contrary to my point above, a few of such experiments have reached the same solution (same amino-acid changes). Yet, again, there is nothing in evolutionary theory demanding such thing to be so.

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  67. Eocene,

    Can you show me, for instance in the article misreferenced by Cornelius here, where do the authors introduce non-scientific philosophy into the experiments?

    If you don't want to do that, where is undue philosophy introduced in the observation that we can breed dogs, or cabbages, or canaries, or whatever?

    Or, where is undue philosophy introduced when we observe that if all the offspring of some living form survived they would quickly overcome the planet?

    Or where is undue philosophy introduced when we observe that best adapted individuals of such offsprings survive?

    Or where is undue philosophy is introduced when we observe that characters vary in a population?

    Or where is undue philosophy introduced when we see that such variation gives a sub-population an edge in somewhat new environments over other individuals?

    Or where is undue philosophy introduced when we observe that the selected subpopulation, when it inter-breeds, move the variation of the advantageous character to a different "zone" attaining even better adaptation?

    Or where is undue philosophy introduced when we observe that the improvement above is due to recombined genes mixed when the selected individuals mate?

    It would be an excellent idea if you could also show me how those observations depend on us knowing how life started.

    That would be an excellent start for us to learn about the evil of those "evolutionists." Just show me where any of those above is not scientific. We can add other items later. I just want to start with some very basics.

    Thanks.

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  68. Negative Entropy: "There are viruses called phage that can jump from one to another bacterium and carry genes among them"

    Yes, but they carry genes that already exist.

    Negative Entropy: "there is the possibility for taking DNA from their environments"

    again, already existing DNA.

    Negative Entropy: "there are horizontally-jumping elements, such as transposons and plasmids"

    Do you get my point yet? You're appeal to "other" bacteria or DNA resources outside the test tube has nothing to do with the process you claim generates the sequences, it's just an appeal for a larger sample size. Mom, where does milk come from? Walmart honey.

    The point is that bacteria can give us a much larger number of "selection events" that we can use to avoid having to wait whale lifetimes. The only differences might be mutation rates at various places in the genome. But we should be able to account for these eventually (certainly before waiting for thousands of generations of whales).

    And if the result in the test tube isn't satisfying, you can always compare to the wild type again, and see the differences your appealing to. If you claim they won't be retained because of differing selection pressure, you also undercut your original objection. I think you can see that right?

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  69. This comment has been removed by a blog administrator.

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  70. John,

    You are missing the point and going for a different target. Your claim was that I was not thinking properly abut the limitations of these experiments. As you can see, I was. Limited experimental conditions do limit the availability of evolutionary avenues. Also, the opportunity for horizontal gene transfer is akin to sexual recombination. I was not confused as you assumed.

    As for your new point. You can call them "pre-existing" genes as much as you want, but you can't deny that these other genes suffer mutations of their own. You can't deny that these genes provide other avenues and opportunities for evolution. One of them recombination with mutations occurring in other populations. You can't deny that the experimental setting limits the number of mutations available at any given time, and the opportunities for recombination with different versions of a gene. You can't deny that the experimental setting limits the kinds of mutations that could survive, nor that there is limited variability of environments (thus of selectable mutations). Sure point mutation is one way for generating gene variability, but it is not the only one, and we are missing the richness of selecting environments. Yes, bacteria allow us to experiment in ways slow-growing organism don't, but there are inherent limitations to the experiments. If they found ways of producing microenvironments within a flask, if then they were able to introduce jumping elements ... Yet, it still worked for that citrate thing, right?

    So, no, I am not appealing to sample size, I am appealing to the natural settings having potential for generating diversity beyond what those experiments can hope to achieve given their inherent limitations.

    In wild types I do see differences in different lineages of different populations belonging, still, to the same species. I am not talking in vacuo. I just can't describe all of it in a few paragraphs. Most importantly if that was not your point. Your point, again, was that I was mistaken in thinking that bacteria can have sex. I answered: sure they can, but not in these experimental conditions, or not as productively.

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  71. natschuster: A protein has to function well enough to be biologically viable. It isn't enough to just function at all. Did the proteins produced in the experiment function well enough?

    The proteins in the experiment functioned well enough to produce infectivity of E. coli. Viruses don't need to eat, drink, or go to the bathroom, so if they can find a host, infect it, and replicate, they're golden. The virus would indeed be subject to competitive exclusion in areas where it was in competition with the wild phage. But the goal of the study was to look at protein emergence and how (partly) randomized proteins could evolve through mutation and selection to increased fitness. Unfortunately for these lines of study, we would have to assume the fitness landscape we see today is similar to the one pertaining when the protein first evolved. In this case, the protein would have first evolved in a world where E. coli was naive to the phage in question. For many possible sequences, phage fitness could have been much greater and the fitness landscape more forgiving.

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  72. anaxyrus:

    ===
    The first proteins arose in a world without the antagonistic ecology we are used to. Fitness landscapes would not have been this rugged.
    ===

    I didn't know that.

    ===
    Proteins we would consider highly dysfunctional today could have worked just fine in that world. Proteins and fitness landscapes evolved together over time. This particular landscape under study would be expected to be highly rugged as it is a product of a coevolutionary arms race between increasingly infective viruses and increasingly resistant bacteria over time.
    ===

    There is no scientific evidence to support these assertions.

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  73. oleg:

    ===
    With the library of a modest size, the protein fitness reached 52% of the native one.
    ===

    Logarithms are wonderful, aren't they?

    ===
    Increasing the library to 10^70 does not do much to improve on that: by the authors' estimate, the fitness will only bump up another 3% to 55%.
    ===

    And you think this is a good result?

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  74. Negative Entropy: You are missing the point and going for a different target.

    Is it possible that you aren't thinking critically enough about what I'm saying and so you think I'm addressing a different issue?

    Negative Entropy: Your claim was that I was not thinking properly abut the limitations of these experiments. As you can see, I was.

    No, you appealed to LGT as if that was a better source of genes than those produced by random mutation. While you may be dissapointed that Lenski (I didn't know you were referring to this study, but it's also a good example) used a strain that was strictly assexual, that was done precisely to observe what could be developed without help from genes that did not come from the original clone.

    You are either asking for the ability to borrow genes from the rest of the wild type which are not under directed selection and so are LESS likely to have the type of genes in question to be selected for OR you are appealing to a larger population under the SAME conditions... a larger sample size. I was offering you an out, thinking perhaps that you were thinking about sexual selection, where there needs to be seperation between groups to make selective sweeps more likely, not something that happens in the same test tube. Since you were not thinking that way, I still don't understand your appeal for contact with the DNA of even MORE bacteria to be anything more than an appeal for a larger sample size.

    Negative Entropy: "As for your new point. You can call them "pre-existing" genes as much as you want, but you can't deny that these other genes suffer mutations of their own."

    Yes and including a larger population size with those genes might very well be like imagining a population of whales that, for example, might fill the solar system. Or given the 4 strains that started hypermutation, who knows, maybe the milky way. But unfortunately, whales can only survive on Earth, and in the ocean at that. The question you need to ask yourself is, would a milky way sized population of whales evolve from dogs faster or slower than only the amount that could fit in the ocean?

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  75. Negative Entropy: "You can't deny that these genes provide other avenues and opportunities for evolution. One of them recombination with mutations occurring in other populations. You can't deny that the experimental setting limits the number of mutations available at any given time, and the opportunities for recombination with different versions of a gene."

    Nor do I! Again, you are appealing for gene resources to a wild type even less likely to develop them then the culture you are constantly pushing the citrate on (and I'm still being generous by letting you imagine that an entirely new citrate metabolism pathway "emerged" rather than breaking the existing operon that shuts down aerobic utilization). You seem to be arguing that the E. Coli might have evolved some radically new functions if they had retained contact with the wild type. But I'll be real bold and predict no. Mostly because wild type E. Coli hasn't done so. Mostly because of the rich environments you're about to appeal to.

    Negative Entropy: "You can't deny that the experimental setting limits the kinds of mutations that could survive,"

    Yes, when the shoe is on the other foot, you are fond of calling this "Natural Selection" the super non-random inventor of all cellular machinery.

    Negative Entropy: "nor that there is limited variability of environments (thus of selectable mutations)."

    Thus you are confusing the cause of mutations (which environment was it that had heat and cosmic rays again?) with your desire to have the environment retain the ones you want. Lenski himself proposed that every possible point mutation that could have occurred in the genome did so (I think multiple times). Also, dogs that like to play along the riverbanks might be seen as limiting the variability of environments. But that's the claim, the ones that started playing in the water got stuck in whale form!

    Negative Entropy: "Sure point mutation is one way for generating gene variability, but it is not the only one, and we are missing the richness of selecting environments."

    Care to guess what happens when you dump those flasks back in to suckle from the environmental richness available to the wild type?

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  76. Negative Entropy: "Yes, bacteria allow us to experiment in ways slow-growing organism don't, but there are inherent limitations to the experiments."

    Yes, bateria don't have the lifespans of dogwhales. But we know how to do long division. Thankfully they mutated a whole lot faster too!

    Negative Entropy: "If they found ways of producing microenvironments within a flask,"

    Then you would be able to hope for what precisely? It sounds like you are close to making a prediction here. Dare me to take the other side!

    Negative Entropy: "if then they were able to introduce jumping elements"

    Oh you're sooo close, because they actualy ARE able to do this part! Unfortunately, the researchers wanted to test the power of random mutations to change proteins or produce new ones and not draw from ones that already existed (like you want to).

    Negative Entropy: "Yet, it still worked for that citrate thing, right?"

    If by worked, you mean breaking a suite of genes that shut down pre-existing citrate metabolism when oxygen is available, then yeah, mutations destroy all kinds of things. Lucky for E. Coli, it was drowning in citrate, a new requirement for this strain to outcompete the wild type. How robust! But it sounds so much more full of wonder when we say, it "gained the ability to metabolize citrate" and hope the jargon turns funders away from investigating what actually happened.

    Negative Entropy: "So, no, I am not appealing to sample size,"

    I think you are, you're just imagining that something more beneficial than the ability to break down more citrate in the presence of citrate might develop in some other environment not under selection pressure to utilize citrate and then be gained by lgt and that that doesn't depend heavily on population size. But since any such ability would itself come around by random mutation (under your theory), you're just pushing the discovery problem on to something that does depend, in the end, on a larger population size.

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  77. Negative Entropy: "I am appealing to the natural settings having potential for generating diversity beyond what those experiments can hope to achieve given their inherent limitations."

    A high concentration of citrate was natural in this study. What is your standard for natural? What exactly is in the current wild type environment that has the potential to generate diversity besides random mutation?

    Negative Entropy: I just can't describe all of it in a few paragraphs.

    I know for sure.

    Negative Entropy: "Most importantly if that was not your point. Your point, again, was that I was mistaken in thinking that bacteria can have sex."

    It was certainly not "my point", in fact, it was the very last words of that post and they were, "PERHAPS you're thinking of speciation events that apply to sexually reproducing species?" I think you just saw that part and stopped thinking about the implications of everything previously discussed and chose to focus on the part that would be a terrible slight to a researcher such as yourself. I think you just need to decide whether evolution proceeds more rapidly in a small population or a large population. It's not my theory. You appeal to small populations when you need fixity and you just end up breaking genes, then you appeal to large populations when you want new DNA, as if that DNA could have been selected from some other non random method and as if it is somehow unavailable to you now, but you just get diminishing returns. Again, as I said, the wild type E. Coli is always available for comparison and competition so just show us!

    Negative Entropy: "I answered: sure they can, but not in these experimental conditions, or not as productively."

    I still am unable to see the roads to success that you must be seeing and so I imagined you must have been appealing to some type of allopatric speciation event or something. That still brings us back to your original quote though;

    Negative Entropy: ""But also think how unrealistic it is to expect this to be any quicker if we are denied, by the experimental setting, enough variety of bacteria within each flask for taking different routes towards different solutions."

    Perhaps you can describe how much more variety you would like than every possible point mutation that could have occured. There's certainly a lot of variety now. Let's do some thought experiments! Would you like more vials not descened from the same clone? Strains that can take advantage of conjugation? LESS citrate or NONE in some environments? I can't really tell what your saying when you're not specific. What kind of micro environments would you like? What are you predicting precisely if you get everything you want?

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  81. Cornelius Hunter:

    ANAXYRUS:
    "The first proteins arose in a world without the antagonistic ecology we are used to. Fitness landscapes would not have been this rugged."
    *****

    CORNLIUS HUNTER:
    "I didn't know that."
    ===

    Well actually neither does he, but never underestimate the power of a good story telling Sage with Hollywood flair abilities.
    ---

    Cornelius:

    ANAXYRUS:
    "Proteins we would consider highly dysfunctional today could have worked just fine in that world. Proteins and fitness landscapes evolved together over time. This particular landscape under study would be expected to be highly rugged as it is a product of a coevolutionary arms race between increasingly infective viruses and increasingly resistant bacteria over time.
    ****

    CORNELIUS HUNTER:
    "There is no scientific evidence to support these assertions."
    ===

    I've never understood the double standard here. Why is it that an when an evolutionist "assumes" , "asserts" or "speculates" , it's considered SCIENTIFIC. But if someone believing in creation or intelligent design "asserts" , "assumes" or "speculates" , it's UNSCIENTIFIC ???

    In fact a paper earlier last year on conditions of OOL claims they ultimately have no idea of those early conditions. Could it be that those scientists don't have access to the data, evidence and proof that only Talkorigins.org or richarddawkins.net or any other internet debate forum has privy to ???

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  82. ==========
    anaxyrus: Proteins we would consider highly dysfunctional today could have worked just fine in that world. Proteins and fitness landscapes evolved together over time. This particular landscape under study would be expected to be highly rugged as it is a product of a coevolutionary arms race between increasingly infective viruses and increasingly resistant bacteria over time. 
    =====

    Cornelius Hunter: There is no scientific evidence to support these assertions.


    Fitness is context dependent, with the biotic environment an important part of that context. You cited some evidence of this yourself on this blog: where we have TTX+ newts, we have TTX-resistant garter snakes. Garter snakes trucked into Oregon from Ohio would find their fitness suddenly reduced; ion channel proteins with low fitness in Oregon conversely have higher fitness in Ohio. In the specific case, coevolutionary arms races between phages and bacteria are documented in the literature.

    Patterson, S. et al. 2010. Antagonistic coevolution accelerates molecular evolution. Nature 464:275-278.

    Abstract
    The Red Queen hypothesis proposes that coevolution of interacting species (such as hosts and parasites) should drive molecular evolution through continual natural selection for adaptation and counter-adaptation. Although the divergence observed at some host-resistance and parasite-infectivity genes is consistent with this, the long time periods typically required to study coevolution have so far prevented any direct empirical test. Here we show, using experimental populations of the bacterium Pseudomonas fluorescens SBW25 and its viral parasite, phage Phi2 (refs 10, 11), that the rate of molecular evolution in the phage was far higher when both bacterium and phage coevolved with each other than when phage evolved against a constant host genotype. Coevolution also resulted in far greater genetic divergence between replicate populations, which was correlated with the range of hosts that coevolved phage were able to infect. Consistent with this, the most rapidly evolving phage genes under coevolution were those involved in host infection. These results demonstrate, at both the genomic and phenotypic level, that antagonistic coevolution is a cause of rapid and divergent evolution, and is likely to be a major driver of evolutionary change within species.

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  83. Eocene: In fact a paper earlier last year on conditions of OOL claims they ultimately have no idea of those early conditions.

    If they truly have no idea about conditions on early Earth, they should walk across campus to the geology library.

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  84. Eocene: I've never understood the double standard here. Why is it that an when an evolutionist "assumes" , "asserts" or "speculates" , it's considered SCIENTIFIC. But if someone believing in creation or intelligent design "asserts" , "assumes" or "speculates" , it's UNSCIENTIFIC ???

    Scientists are extrapolating from observed evidence using mathematics, logic, and supported theory. Creationists start with Bronze age mythos, and extrapolate based on "I was never a monkey." So for that reason, plus the scare quotes, and the all caps, and the triple question marks.

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  85. Cornelius wrote: Logarithms are wonderful, aren't they?

    Sure they are. We use them in places where we have to deal with many orders of magnitude and where multiplication, rather than addition, is the typical math operation. Working with logarithms changes multiplicative quantities into additive and gets rid of the bulky order-of-magnitude notation.

    Entropy is defined as the logarithm of the number of microstates, remember?

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  86. Eocene -

    "Of course I do, especially since I have run controlled neutral potting media experiments in a closed nursery seedling germination and at the same time experimenting with mycorrhizal innoculations with regards rooting benefits in the media."

    Well good for you. So then perhaps you can explain how you so fundamentally misunderstood the word 'controlled' in the expression 'controlled experiment' as to utter this:

    "I believe the official mandate of evolution being FACT takes care of the controlled part, don't you Ritchie?"

    --------------------------------------------

    "I've never understood the double standard here. Why is it that an when an evolutionist "assumes" , "asserts" or "speculates" , it's considered SCIENTIFIC. But if someone believing in creation or intelligent design "asserts" , "assumes" or "speculates" , it's UNSCIENTIFIC ???"

    Perhaps because 'evolutionists' understand the distinctions that make assertions scientific. Such as falsifiability and naturalism. Things ID proponents never provide among their empty, hollow claims.

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  87. John,

    It is not my theory either.

    Let us recount:

    Neil said something like "what if 3, 4, 10 mutations are required"?

    Since we are asking rhetorical questions I answered:

    What if under a different context only one or two are required?

    Then you gave me a couple sentences that are meaningless to the point, and finish with a longer paragraph about me been confused about sex in bacteria, and affirming that each bacteria is its own route. So, I answer that. Then, since I answered that, you come with "those are pre-existing genes," "that is pre-existing DNA" (or something to the effect).

    Unless I missed something, the experiments with E. coli are not about making brand new genes, so this is a new topic on your part, and misses the point that bacteria actually have sex and other avenues than living surrounded by an almost even, genetically poor population. Yes, mutations make for variability and variability makes for evolutionary avenues, but we were not talking about origin of genes, nor about origin of first proteins that far, were we?

    So, is that an introduction of new problems on your part yes or no?

    As for the roads to success. Let me give you a metaphor, our technologies started very slowly. First fire, then wood making, then combinations of water/fire/wood to bend wood without breaking it, fire to extract metals, purifying metals, new ideas of how to mix and match metals, then thing is, the starts were very slow, we had fire alone for much longer than we developed technologies based on it. The thing is, as we built some basics, we started building on top of such basics, and on top, and on top, and now, technologies advance so fast we have witnessed and keep witnessing technological innovations to a point that we are no longer surprised (unfortunately, because the feeling was so beautiful). Now we expect new technologies to arise constantly.

    Well, evolutionarily speaking it is the same, the beginnings must have been slow, every evidence shows this to be so. Around one billion years before first evidence for life, huge gap before we see any multicellular thing. Anyway, once we have genes in the environment, there is little need to invent proteins from complete scratch. Genes are co-opted, protein domains shuffled, shuffling plus slight re-inventions, divergence, existence of many versions derived from some genes, lots and lots of processes going on.

    Do we have any evidences about those? Sure, we have traced HGTs and recombinations, and domain shuffling, and such. We have seen that new genes are rarely invented, divergence is the "preferred" way (the most probable way, since HGT is so easy to come by--in prokaryotes and unicellular eukaryotes at least). Experiments on directed evolution show that recombination accelerates the finding of new or improved functions by orders of magnitude (first time I saw a publication on this, it was too fast for my liking, meaning I was skeptical, but I was shown wrong pretty quickly). From my own work, seems like regulatory interactions are among the most "evolvable" (actually "most evolved"), for instance, meaning that not everything is about mutations affecting protein sequences.

    So, yes, there are many avenues to innovation. But understanding them requires a bit of studying.

    Now, John, I am not answering you for winning arguments, but for understanding positions. There is no way that creationist "arguments" that I can so easily identify as propaganda and quackery will change my mind. I don't expect you to change yours. All I aim for is clarification. If you decide that evolution cannot use any recombination, domain shuffling, and whatever, well, that is up to you. But that does not mean it does not happen.

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  89. Eocene wrote:

    I've never understood the double standard here. Why is it that an when an evolutionist "assumes" , "asserts" or "speculates" , it's considered SCIENTIFIC. But if someone believing in creation or intelligent design "asserts" , "assumes" or "speculates" , it's UNSCIENTIFIC ???

    Eocene,

    Here's two questions I asked Cornelius on the previous thread, which I'll pass on to you.

    I have a simple question for you: do you think there a solution to the problem of induction? If so, what do you think the solution is?

    However, I'm guessing that neither you or Cornelius will answer these questions as they would would reveal this really isn't a double standard after all.

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  90. Negative Entropy: "Since we are asking rhetorical questions I answered:"

    Since you say you are just aiming for clarity now, what was your answer to his rhetorical question?

    Negative Entropy: "What if under a different context only one or two are required?"

    We already have experiments showing what would happen in this context so there is no need to wonder. He's specifically talking about situations where this is not the case. It's perfectly fair for you to make the claim that different gene families are never separated by more than two mutations at a time. Is that your claim?

    Negative Entropy: "Then you gave me a couple sentences that are meaningless to the point,"

    They were meaningless to the point you want to focus on, but not to the point he was making about dogs becoming whales.

    Negative Entropy: "and finish with a longer paragraph about me been confused about sex in bacteria, and affirming that each bacteria is its own route. So, I answer that."

    Incorrectly, as each bacteria is free to mutate however it might. Your appeal to HGT is an appeal to things that you also claim came from random mutation. The point (quite belabored at this time) is that a whale like creature would require hosts of new genes and proteins, while you want to focus on reshuffling alone.

    Negative Entropy: "Unless I missed something, the experiments with E. coli are not about making brand new genes"

    What you missed is Lenski claiming this was similar to 400,000 years of research on larger organisms. So when you say it's not about making brand new genes, you're saying all that's left for you to say, since, if 10 brand new genes WERE produced, you would all be dancing around claming the study WAS about making brand new genes.

    Negative Entropy: "so this is a new topic on your part, and misses the point that bacteria actually have sex and other avenues than living surrounded by an almost even, genetically poor population."

    Or was it Neal's original point, with you now claiming that Lenski was wrong in his comparison.

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  91. Negative Entropy: "Yes, mutations make for variability and variability makes for evolutionary avenues, but we were not talking about origin of genes, nor about origin of first proteins that far, were we?"

    We're talking about whether doglike can evolve into whalelike in a given amount of time. I'm going to go out on a limb and say new genes and proteins ARE required. Will you take the other side of that prediction?

    Negative Entropy: "So, is that an introduction of new problems on your part yes or no?"

    No.

    Negative Entropy: "As for the roads to success. Let me give you a metaphor, our technologies started very slowly."

    Ah yes, when natural examples won't suffice, turn to intelligent design. I'll spare you a long reply in hopes you can uncover the error yourself.

    Negative Entropy: "Anyway, once we have genes in the environment, there is little need to invent proteins from complete scratch. Genes are co-opted, protein domains shuffled, shuffling plus slight re-inventions, divergence, existence of many versions derived from some genes, lots and lots of processes going on."

    From what I can see, gene families look alot like the fossil record, very clustered with not a lot of in between forms. Are you predicting that with more solved structures we will find a continuum of intermediates?

    Negative Entropy: "We have seen that new genes are rarely invented, divergence is the "preferred" way (the most probable way, since HGT is so easy to come by--in prokaryotes and unicellular eukaryotes at least)."

    I'm sorry, but is this an observation or a prediction? Divergence... to a new gene right?

    Negative Entropy: "Experiments on directed evolution show that recombination accelerates the finding of new or improved functions by orders of magnitude (first time I saw a publication on this, it was too fast for my liking, meaning I was skeptical, but I was shown wrong pretty quickly)"

    When you say "finding" don't you really mean "sharing"? When you say "new" don't you really mean "existing"? If you hand me a peanut butter and jelly sandwich, I will obtain it orders of magnitude faster than if I have to make it myself. Hmm I'm hungry.

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  92. Negative Entropy: "From my own work, seems like regulatory interactions are among the most "evolvable" (actually "most evolved"), for instance, meaning that not everything is about mutations affecting protein sequences."

    Yes, the old dogma is dying, but we still have the ability to look at and compare protein domains, shuffled though they may be.

    Negative Entropy: "So, yes, there are many avenues to innovation. But understanding them requires a bit of studying."

    Well you go off to your studies then. Or if you mean me, then just tells me the answer. No need to be coy. I've already studied the mechanisms you describe but find them lacking in ability to turn dogs into whales in anywhere near the given amount of time. Maybe next time they will be a little more careful when imagining things about the next Packicetus.

    Negative Entropy: "If you decide that evolution cannot use any recombination, domain shuffling, and whatever, well, that is up to you. But that does not mean it does not happen."

    Well, Huff! Since I supposedly ignored recombination, domain shuffling, and whatever "whatever" means, then you have clearly done your best to crack through my ignorance. I clearly have much studying to do, but while I'm at it, could you perhaps elucidate what "whatever" means and see if you're not really just placing your faith in it's gene generating power? You might save me a whole lot of work!

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  93. John,

    Please try not to introduce more nonsensical creationist rhetoric. Nobody asked about dogs becoming whales. Otherwise I would have just answered about how twisted their understanding of evolution is. If you do this, you give me too much to clarify, and we will never reach anything.

    Neal's comment had two components:

    One "what if something needs more mutations?" Such question has an easy answer "What if a different background does not need as many mutations?" A different solution to a problem can exist for a different organism. Right?

    The second component was somewhat derived from the first (though in reality it does not necessarily follow) to say "and are we supposed to believe that a terrestrial animal evolved into a whale in whatever generations?" My answer was clear there too. I can re-answer as follows: You don't have to believe it. Look at the evidence and decide.

    So now piecemeal:

    He's specifically talking about situations where this is not the case.

    I am specifically talking about situations where if for one organism it is not the case, it could be for another.

    It's perfectly fair for you to make the claim that different gene families are never separated by more than two mutations at a time. Is that your claim?

    Of course not. We know that gene families have members separated by so many mutations that they are hard to identify as members of the same family. What I am saying is that this natural variability allows for much more than would be available within this experiment. You have some messed up understanding here. Nobody expects that every organism will be able to survive any environmental challenge (just in case this is where you are going).

    cont ...

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  94. John cont 2 ...

    Incorrectly, as each bacteria is free to mutate however it might.

    No, it is not. If the mutations are awfully deleterious, there is no survival. At any moment, we can only see mutations that were neutral, semi-neutral, or beneficial. The growth conditions in Lenski's experiments are not very suitable for a lot of variants to co-exist within a flask. But you affirmed that bacteria are their own route, I answer no. How is that wrong exactly?

    Your appeal to HGT is an appeal to things that you also claim came from random mutation.

    Not from random mutation, but from any combinations of genetic drift (neutral and semi-neutral), random fixation, and from selection. Yes, the background mutations are random, but their presence is not.

    The point (quite belabored at this time) is that a whale like creature would require hosts of new genes and proteins,

    Well, you would have to be able to demonstrate that this is actually required. I will wait until someone decides to sequence the whale genome. I bet gene duplications and regulation will be the answer. But let us wait and see.

    while you want to focus on reshuffling alone.

    I don't see why not, but we were talking about bacteria. Sure, still, reshuffling might have taken a part in whale evolution.

    What you missed is Lenski claiming this was similar to 400,000 years of research on larger organisms.

    Yep, under very limited conditions, as it should be for experimental stuff. Otherwise you don't know what to attribute to which process. Right?

    So when you say it's not about making brand new genes, you're saying all that's left for you to say, since, if 10 brand new genes WERE produced, you would all be dancing around claming the study WAS about making brand new genes.

    No, I would doubt the experiment a lot (perhaps, losing another battle in the process, as I have been wrong before). But the aims of the experiments are clear. Go search and you will see. Again, the citrate thing was unexpected (whether you want to believe it to have been unexpected or not). On looking backwards, maybe it should not have been unexpected, but for starters it was.

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  95. John cont 3 ...

    Ah yes, when natural examples won't suffice, turn to intelligent design. I'll spare you a long reply in hopes you can uncover the error yourself.

    This would be "an error" only if I assumed that you are here for the rhetorics, not for understanding. Let me know. If you are talking to win empty rhetorical points. I will just stop thinking you are talking in all honesty and answer accordingly. Otherwise just tell me if the metaphor was useful or not. Save the B.S. Now, I had more to answer, a beautiful chat about protein structure and wrong paradigms, but I will wait until I know if you will keep it honest or jump to rhetorics and creationist quackery instead. I mean, "dogs to whales," I could assume an honest mistake, but this one is plain and direct quackery.

    Let me know.

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  96. Negative Entropy: "Please try not to introduce more nonsensical creationist rhetoric. Nobody asked about dogs becoming whales."

    Neal: "Yet we are to believe that a land animal lineage evolved into a full blown whale in less than a million generations?"

    Wikipedia (Pakicetus): "...It was first restorated as a semiaquatic mammal similar to a crocodile (at the time based on some skull fragments), but is now known to have been a terrestrial, wolflike mammal."

    I'm sorry, I must have thrown you off track by saying doglike instead of wolflike. Please forgive me the thousand or so years this throws the calculations off by. But yes this is what evolutionists now claim because they accidentally took skull fragments and saw hope to fill in a spot in whale evolution.

    Negative Entropy: "A different solution to a problem can exist for a different organism. Right?"

    Your objection is only satisfying if you are claiming smooth 2 mutation differences between all protein families. Perhaps you are thinking, "no this gene evolved under completely different circumstances and is completely new to the organism" but in the end, even if that gene is transfered to the new organism, then that would be 2 or less mutations different by definition.

    A simple way to understand it is that you cannot go on sharing forever, at some point, you need gene creation, and at that point, you have no better work horse than random mutation and natural selection... the same processes available in that flask.

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  97. John,

    You said dogs to whales twice, "doglike" only once. This is why I gave you the benefit of the doubt. Yet, then you came with the "intelligent design" rhetoric. What am I supposed to think about you after that?

    For whales from terrestrial ancestors we have more than what we have in that flask. We have the allele variability and sexual reproduction, while the experiment started with uniform E. coli cells, we have from 20 to 30 thousand genes, jumping elements, tandem DNA duplications, and a variety of controlling sequences and regulatory proteins, while the E. coli had around 4,000 to 4,500 genes (from memory, might be off a bit). But, again, I don't care. If the evidence shows that whales did evolve from terrestrial animals, they did. How this worked at the genetic level is an excellent question, but the evidence will not go away. If the genetics showed new genes, well, surprise surprise, but, the evidence of their terrestrial ancestry is still there. As I have said before, no amount of questioning the power of mutations, duplications, divergences, and so, will erase the fact that we can get such variety of dog breeds. I don't see how such questioning will make the whale history disappear.

    As for directed evolution. If I say "improved" it means existing function, only much better. If I say "new," it means new. If I say "finding," I mean finding, not sharing. Despite I assumed honesty on your part, I was careful enough with my words.

    Of course, looking forward, life can go on sharing and mutating and recombining for as long as life is sustainable in the planet. New functions don't need to come from the novo gene formation. The genetic repertoire is unimaginably big, thus little new gene appearance might be necessary. Going backwards, at some point(s) new genes have appeared, a are appearing now. How the first ones did? I don't know. I can only speculate, but will spare you the exercise. We have seen a few new genes appearing (yes, observation), but that has been the exception, rather than the rule. That still depended on existing processes, such as existing DNA pieces, insertions, recombination, and, yes, mutations. Still, the new genes produced actually new protein.

    Your objection is only satisfying if you are claiming smooth 2 mutation differences between all protein families.

    That would be ridiculous on my part. Two mutations are never enough to call a protein into a different family. How are you defining "protein family"? By function?

    Perhaps you are thinking, "no this gene evolved under completely different circumstances and is completely new to the organism"

    While I agree that a gene evolving elsewhere would be new to the organism, what I am thinking that the "quickest" solution to a problem might need 10 mutations under one background (all in a particular gene, or dispersed among several genes, whatever), but it might require only one mutation in a completely different gene given its background (background meaning other activities in a host cell).

    but in the end, even if that gene is transfered to the new organism, then that would be 2 or less mutations different by definition."

    My answer is pertinent because if it is about speculating for problems requiring three to ten mutations before you see any benefit, then it should be acceptable to speculate that the organism in question will lose the "race" against an organism whose background has it closer to solving the same problem, even if by a different route.

    Note again, that we were not talking about new genes by the way most scientists define new genes. You seem to define them by their specific functions, thus the miscommunication (if I assume that the creationist rhetoric was accidental, but now I am biased, meaning I don't think it was).

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  98. Negative Entropy: "You don't have to believe it. Look at the evidence and decide."

    I've looked at the evidence and it seems to show the wolflike to whalelike transition to be nearly impossible. I might as well believe that the tooth fairy created whales from cheese. But perhaps you have information others don't that makes it seem more plausible.

    Negative Entropy: "I am specifically talking about situations where if for one organism it is not the case, it could be for another."

    Incidentally, does that mean you think HGT played a large role in the wolflike-whalelike transition?

    Negative Entropy: "Of course not. We know that gene families have members separated by so many mutations that they are hard to identify as members of the same family."

    When I say 2 mutations "AT A TIME", what I mean is that one gene can mutate into another with only two mutations at any one time, not 2 mutations total. But thanks for making me clarify this. It really helps me realize how much I'll need to invest in this conversation before I can get any new information.

    The point is that when you say, "what if some other organism is so close that it is only 2 mutations away" it seems to imply that you believe random mutation will always find a way to provide that so you don't have to worry about when it's 250 steps away.

    Negative Entropy: "You have some messed up understanding here. Nobody expects that every organism will be able to survive any environmental challenge (just in case this is where you are going)."

    No, your hunch was right, I'm not pursuing that argument. We probably saved 30 minutes right there.

    John: "Incorrectly, as each bacteria is free to mutate however it might."

    Negative Entropy: "No, it is not. If the mutations are awfully deleterious, there is no survival."

    But of course, for an organism to die because of a mutation, it must first have had the freedom to mutate that way... a pretty elemental proposition, no?

    Negative Entropy: "The growth conditions in Lenski's experiments are not very suitable for a lot of variants to co-exist within a flask."

    They are if the various mutations provide no selectable advantage yet. After that, then no, there will differential reproduction.

    Negative Entropy: "But you affirmed that bacteria are their own route, I answer no. How is that wrong exactly?"

    Because any bacteria in a clonal strain has an equal chance of hitting any of the possible mutation combinations that provide the first selectable advantage.

    Negative Entropy: "Not from random mutation, but from any combinations of genetic drift (neutral and semi-neutral), random fixation, and from selection. Yes, the background mutations are random, but their presence is not."

    Yes it is. Just because it was selected after randomly appearing, does not mean it then didn't randomly appear.

    more later... wait or continue if you wish :D

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  99. Oh what a mess you made John.

    I've looked at the evidence and it seems to show the wolflike to whalelike transition to be nearly impossible.

    Then you did not look at the evidence, you looked at something presented by some creationist who withheld important information.

    I might as well believe that the tooth fairy created whales from cheese. But perhaps you have information others don't that makes it seem more plausible.

    Nope, all the information is very public. Just take a look by yourself. Just avoid the creationist quackery.

    Incidentally, does that mean you think HGT played a large role in the wolflike-whalelike transition?

    Are you reading any of my comments or just searching for positions of attack? Oh, I was almost forgetting that you are not looking for answers. See my comments then tell me that your question here was necessary.

    ... jumping lots of other such already answered stuff, and useless rhetoric ...

    Negative Entropy: "But you affirmed that bacteria are their own route, I answer no. How is that wrong exactly?"

    Because any bacteria in a clonal strain has an equal chance of hitting any of the possible mutation combinations that provide the first selectable advantage.


    This would correct about the experiment, but not what we were talking about. Again, in nature bacteria cannot be their own route.

    We could continue, if you ask new questions and stop trying so hard not to understand.

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  100. John,

    Sorry, I missed this more normal point where some clarification might actually occur (unless you don't want it to):

    The point is that when you say, "what if some other organism is so close that it is only 2 mutations away" it seems to imply that you believe random mutation will always find a way to provide that so you don't have to worry about when it's 250 steps away.

    Well, if so then no, I was not trying to imply such. I was saying that it might be 250 steps away for one organism, not for another. But there is no reason to think that evolution will always provide. There might be no organism anywhere close to solve some problem. If so, then such niche/environment/whatever, will not be conquered any time soon.

    But remember we are talking about bacteria and mutations towards a new function (citrate consumption) where any of these mutations provide no advantage unless both mutations are present. That is not exactly whale evolution (or not necessarily). In whale evolution we see lots of steps, but each step has advantages.

    Clear finally? Two different problems.

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  101. John:
    ====
    But yes this is what evolutionists now claim because they accidentally took skull fragments and saw hope to fill in a spot in whale evolution.
    ====

    The current state of knowledge on the skeleton of Pakicetus (Fig. 2):

    http://www.faculty.virginia.edu/bio202/202-2002/Lectures%2020202/thesissen%20et%20al%202001.pdf

    Yeah, fragments... making up most of the skull. Uh-oh.

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  102. Geoxus,

    Thanks. Nice article to have in my for-class collection.

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  103. I applaud you, Dr. Hunter, for demonstrating the silliness that is Intelligent Design Creationism by pretending to argue against evolution.

    You go above and beyond, even to the point of fooling Creationists into believing you are one of them. I'm sure your fake arguments refuting evolution, followed by quick and easy to understand rebuttals in the comments are having the effect you hope--giving thinking Creationists a better grasp on the science of evolution and the silliness that is ID.

    Keep up the good work!

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  104. Geoxus: "Yeah, fragments... making up most of the skull. Uh-oh."

    Yeah, minus the flippers this time. But you could probably draw flipper like limbs.

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  105. John: "while you want to focus on reshuffling alone."

    Negative Entropy: "I don't see why not, but we were talking about bacteria. Sure, still, reshuffling might have taken a part in whale evolution."

    The common theme of the comparison was about how likely it would be for Pakicetus to develope something that these bacteria could not.

    Negative Entropy: "Yep, under very limited conditions, as it should be for experimental stuff. Otherwise you don't know what to attribute to which process. Right?"

    It was only limited near the beginning. Lenski said that every possible point mutation that could have occured would have. How many generations of Pakicetus would it take to match that amount of diversity? All the smooth bridges from this protein to that are on their way to being explored and selected for!

    Negative Entropy: "Again, the citrate thing was unexpected (whether you want to believe it to have been unexpected or not)"

    At first I thought you were talking about a different study, but from what I remember, these strains were constantly fed much more citrate than sugar. From what I can tell, that is in line with what evelotionary theories predict. Unfortunately at the molecular level, it seems to have occured by inactivating proteins rather than generating new ones.

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  106. Negative Entropy: "Otherwise just tell me if the metaphor was useful or not. Save the B.S."

    Tell you what, the metaphor might indeed be usefull if you just tell me which part of nature the designers represent.

    Negative Entropy: "but I will wait until I know if you will keep it honest or jump to rhetorics and creationist quackery instead."

    I promise not to curse you back.

    Negative Entropy: "I mean, "dogs to whales," I could assume an honest mistake, but this one is plain and direct quackery."

    No it's shorthand for those types who might give a friendly reading to it. Plenty of evolutionists describe Pakicetus as doglike.

    Negative Entropy: "Yet, then you came with the "intelligent design" rhetoric. What am I supposed to think about you after that?"

    You can act amazed and confused all you want, but this is obviously a forum regarding precisely this issue.

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  107. Negative Entropy,

    You are welcome!

    John:
    ====
    Yeah, minus the flippers this time. But you could probably draw flipper like limbs.
    ====

    Old reconstructions did, new ones don't (google "Carl Buell Pakicetus"). Those silly evolutionists correct themselves when they find new evidence! Ridiculous, isn't it? Anyway, Pakicetus is pretty basal in whale evolution, so plesiomorphic limbs are not surprising.

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  108. John,

    You can act amazed and confused all you want, but this is obviously a forum regarding precisely this issue.

    But we were not talking about intelligent design, and your B.S. rhetoric, you know quite well, is to take an honest metaphor and twist it into

    Ah yes, when natural examples won't suffice, turn to intelligent design. I'll spare you a long reply in hopes you can uncover the error yourself.

    I was trying to make it easier to grasp: evolving proteins should have taken much longer at the beginning than afterwards. Once you have richness of genes around, the probability to evolve an existing gene/protein into some new function becomes higher than that of evolving new proteins from scratch. Innovations are possible to be evolved on top. The simile was with how building a base technology makes it easier to build on top afterwards. I should not need to explain this. If you wanted to understand you would have. But you had to bring the rhetoric. I guess you are proud that we have to be careful how we explain lest you start playing your tricks.

    Also, you know quite well that creationist quacks use the "dogs to cats," "crocoducks" and such ridiculous cartoons of evolution. So using "dogs to whales" makes it easy for me to think you are B.S.ing. I still gave you the benefit of the doubt until you used the "turn to intelligent design" card. What else do you expect but for me to be unpleasantly surprised? In retrospect I should have supposed that you would be this kind of a creationist. But well, now I know.

    Please don't try and answer this one any more. Your pretension that I "act surprised" because you "brought a theme of this forum" betrays a much more cynical dishonesty on your part. Don't make it worse. I am already nauseated. I will try to continue on the science, but will use no metaphors.

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  109. John,

    OK. after reading your new set of comments. I see that we would just continue in circles. So, we are done for now.

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  110. Negative Entropy: "For whales from terrestrial ancestors we have more than what we have in that flask. We have the allele variability and sexual reproduction, while the experiment started with uniform E. coli cells,"

    Yes it started that way, but in a very short time (relatively speaking) you had a huge amount of allele variability in the flask. And you're forgetting that although sexual reproduction can combine the mutations you want in the same organism, unless they already provide selectable advantage (the original issue), they are no more likely to be retained there than any other random mutation.

    Negative Entropy: "we have from 20 to 30 thousand genes, jumping elements, tandem DNA duplications, and a variety of controlling sequences and regulatory proteins, while the E. coli had around 4,000 to 4,500 genes"

    More genes simply reduces the selection coefficient for each gene by the same factor. As for transposons, tandem duplications, controlling sequences and regulatory proteins, these are all found in E.Coli as well, yes?

    Negative Entropy: "But, again, I don't care. If the evidence shows that whales did evolve from terrestrial animals, they did. How this worked at the genetic level is an excellent question, but the evidence will not go away. If the genetics showed new genes, well, surprise surprise, but, the evidence of their terrestrial ancestry is still there."

    This is a very simplistic way of approaching evidence. I did not say there was NO evidence compatible with this event. If fossil A has a particular bone structure more similar to fossil B than average, the evidence is more compatible. But one piece of evidence that falsifies is worth a hundred pieces that seem to support.

    Negative Entropy: "As I have said before, no amount of questioning the power of mutations, duplications, divergences, and so, will erase the fact that we can get such variety of dog breeds."

    I know, imagine how many species paleontologists would name after themselves if we had a fossil for every type of dog breed. Of course maybe not, they did the opposite for chimpanzee fossils for quite a while you know. Ever wonder why?

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  111. Negative Entropy: "I don't see how such questioning will make the whale history disappear."

    To be certain the actual history of whales will remain unaltered. But you are comparing natural selection to very strong directed selection. We know that sustained directed selection of this type can quickly alter appearance and drasticaly reduces fitness usually destroying many genes in the process in a space of time you yourself said would amaze you if even 10 new genes were created. Again, see how long your dog breeds last against even the average mutt, let alone wolves. As you noted before, dead bacteria can't reproduce.

    Negative Entropy: "As for directed evolution. If I say "improved" it means existing function, only much better."

    In the new context, and almost always by breaking regulatory proteins or causing a loss in specificity in some active site.

    Negative Entropy: "If I say "new," it means new. If I say "finding," I mean finding, not sharing. Despite I assumed honesty on your part, I was careful enough with my words."

    Recombination finds new genes more quickly than what? Are you talking about all recombination type events?

    Negative Entropy: "then it should be acceptable to speculate that the organism in question will lose the "race" against an organism whose background has it closer to solving the same problem, even if by a different route."

    What your speculation logically entails, although non-intuitive, is that the genes we see today have morphed to their current form because they were only one or two mutations away from the form needed by some organism at all times. If they require more, you say, well another gene saved the day... but still by only one or two mutations.

    Negative Entropy: "Note again, that we were not talking about new genes by the way most scientists define new genes. You seem to define them by their specific functions, thus the miscommunication (if I assume that the creationist rhetoric was accidental, but now I am biased, meaning I don't think it was)."

    Right. I probably don't define scientist the way most "scientists" do either. But anyway, I'm using the word new to mean totally new. But I think I said pre-existing enough times to eliminate any confusion down the line. I find the way you are using the word new to be subject to more ambiguity and usually at the worst possible time.

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  114. John: Recombination finds new genes more quickly than what?

    Than evolution by point-mutation alone.

    John: A simple way to understand it is that you cannot go on sharing forever, at some point, you need gene creation, and at that point, you have no better work horse than random mutation and natural selection... the same processes available in that flask.

    Several times above you seemed to indicate that point-mutation is the only form of variation available for evolution. There are many forms of variation, including recombination and retroviruses. However, most appear to be largely random with respect to fitness.

    John: What exactly is in the current wild type environment that has the potential to generate diversity besides random mutation?

    The only demonstrated correlation between the environment and the sources of variation is the rate of mutation across regions of the genome. There are some interesting possibilities, though, such as mistakes in protein synthesis giving a small "look-ahead".

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  116. Zachriel: "Than evolution by point-mutation alone."

    Definitely, but I want to make sure he's not comparing it to something else.

    Zachriel: "Several times above you seemed to indicate that point-mutation is the only form of variation available for evolution. There are many forms of variation, including recombination and retroviruses. However, most appear to be largely random with respect to fitness."

    Yeah, I thought someone might point that out, but I think it still gives a good idea of the amount of diversity that can arise. Besides, a large part of this issue seems to be how connected the paths between genes are, whether one, two, or 50 or more mutations. Are we appealing ot hopeful monsters again, or no? I'm just trying to get his whole idea so I can evaluate what he's saying.

    Sorry you got caught in the middle of my document dump.

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  119. trying to repost in order.. yuk

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  122. Negative Entropy: "Then you did not look at the evidence, you looked at something presented by some creationist who withheld important information."

    http://www.talkorigins.org/features/whales/ was the last I looked at I think. It seems familiar. But no, I don't generally read creationist literature when researching evidence FOR evolution. Often I talk to evolutionists like yourself. Like right now.

    Negative Entropy: "Nope, all the information is very public. Just take a look by yourself. Just avoid the creationist quackery."

    No one will ever be able to go over all the data, and even then, different people take away different implications. I thought you might be an independent thinker with insights I'd not seen before. I'm just asking for what YOU find convincing... precisely.

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  123. John: "Incidentally, does that mean you think HGT played a large role in the wolflike-whalelike transition?"

    Negative Entropy: "Are you reading any of my comments or just searching for positions of attack?"

    I was just wondering if you thought Pakicetus gained a significant portion of it's genes from "another" organism along the way. Isn't that a reasonable inference to draw from your statement? But as you can see, I'm very methodically reading your comments.

    Negative Entropy: "This would correct about the experiment, but not what we were talking about. Again, in nature bacteria cannot be their own route."

    Then why do you say they are here,
    Negative Entropy: "But also think how unrealistic it is to expect this to be any quicker if we are denied, by the experimental setting, enough variety of bacteria within each flask for taking different routes towards different solutions"

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  124. Negative Entropy: "But remember we are talking about bacteria and mutations towards a new function (citrate consumption)"

    It seems that "new function" is how you've decided to file it away. But citrate consumption is not a new function in E. Coli. otherwise how could you break the genes that turn it off?

    Negative Entropy: "where any of these mutations provide no advantage unless both mutations are present. That is not exactly whale evolution (or not necessarily)."

    How could you POSSIBLY know that? It seems to be an EXTREMELY constrained claim. I'm sure I don't know what you mean here. It occured in a genome of 4500, but it's never going to crop up in one that's 20,000?

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  125. Negative Entropy: "In whale evolution we see lots of steps, but each step has advantages."

    Unless someone has sequenced a proto whale genome from fossilized remains, I'll assume this means something like, we found a fossil that had more flipper like paws and so this must have come from genes that gradually morphed no more than 2 or 3 mutations at a time to the current form in whales. "each step has advantages".. compared to what? if you played the tape in reverse, you'd say it was tetrapod evolution and it had advantages because it could forage on land. Do you know the level of shamaan voodoo that branch of "science" goes through? It can't change daily because it's not even that coherent.

    Negative Entropy: "Clear finally? Two different problems."

    No, you'll certainly have to clarify the gene level implications you are drawing from looking at proto whale fossils.

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  126. Negative Entropy: "But we were not talking about intelligent design, and your B.S. rhetoric, you know quite well, is to take an honest metaphor and twist it..."

    I did not restate your metaphor in any way. The misfortune of using a metaphor where everything is designed is yours. You can laugh at something you did accidentally, or get angry if you feel you betrayed a weakness in a metaphor you once found convincing. Only you know what you knew. It seems often that evolutionist turn to these types of explanations in desperation in place of directly discussing the facts they've encountered, so I feared you had finally departed from thinking critically. Apparently you have long ago consigned intelligent design to the dust bin of BS. While I don't agree with all of their tennets, I feel they do make a few good arguments, some of which have implications for the current discussion. I think you've been at this board long enough to realize that. If you felt I was being dismissive, It was probably because I didn't feel like typing a long reply restating direct questions only to be rewarded with more metaphors.

    Negative Entropy: "I was trying to make it easier to grasp: evolving proteins should have taken much longer at the beginning than afterwards."

    Do you agree that this includes the assumption that the search space between functional proteins is not equal on average? Also, DNA repair is "highly conserved"

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  127. Negative Entropy: "Once you have richness of genes around, the probability to evolve an existing gene/protein into some new function becomes higher than that of evolving new proteins from scratch."

    I'm not sure how you arrived at this. Isn't this claim the opposite of the gene duplication claim? If a protein is useful the way it is, isn't it less likely to change into something else than a random sequence that has no stabilizing selection applied to it? It seems like an existing gene requires an additional duplication event to start searching again, while an existing random sequence has already started. "...the copy is then free to mutate, etc. etc..."

    Negative Entropy: "Innovations are possible to be evolved on top. The simile was with how building a base technology makes it easier to build on top afterwards."

    To be sure, any possible modifications to existing proteins are more likely to happen when they exist than when they don't exist. But that does not mean it is more likely to happen than the first emergence of a gene itself.

    Negative Entropy: "I should not need to explain this. If you wanted to understand you would have. But you had to bring the rhetoric. I guess you are proud that we have to be careful how we explain lest you start playing your tricks."

    If you believe we are designed creatures, I completely understand your metaphor. I am proud, and I'm proud of you for any careful explaining you do for me. Yes, since it seems to me that most adherents to common descent are certain of it for often contradictory reasons, I try my best to beg for precision.

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  128. Negative Entropy: "Also, you know quite well that creationist quacks use the "dogs to cats," "crocoducks" and such ridiculous cartoons of evolution. So using "dogs to whales" makes it easy for me to think you are B.S.ing."

    Except that "dogs to whales" pretty much sums up your position. That's what makes me think that YOU GUYS are "B.S.ing" But I will clarify from now on and say doglike or Pakicetus or proto-whale so it sounds less rediculous when you defend it.

    Negative Entropy: "I still gave you the benefit of the doubt until you used the "turn to intelligent design" card. What else do you expect but for me to be unpleasantly surprised?"

    If you were surprised, I'm certain it was unpleasant. I think I would have face-palmed after that one.

    Negative Entropy: "In retrospect I should have supposed that you would be this kind of a creationist. But well, now I know."

    Oh, poor you, I spent over 20 hours on these conversations so I could just spit out caricatures of evolution? If this is how you want to go out, then believe whatever lets you exit fastest. Great, I spent half a work week on you and you didn't tell me one new thing, thanks for all your expertise.

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  129. Negative Entropy: "Please don't try and answer this one any more. Your pretension that I "act surprised" because you "brought a theme of this forum" betrays a much more cynical dishonesty on your part. "

    If you don't want an answer, don't read it, right? Forgive me for making you scroll 10 more clicks. As far as this laundry list you're keeping of my wickedness, I've been ignoring your accusations and trying to focus on the facts for a while now, but since your building longer lists of imaginary slights than evidence for "terrestrial-creature-that-is-dog-like-but-not-a-dog to whale" evolution, the former is starting to interfere with progress on the latter. So let's see, has anyone ever accused you of living in a dream world of victimization? I don't buy it, and it seems like an act you're using to leave in a harumph. Like, Oh NOES, "What am I to believe??" How can I go on when you've twisted my metaphor so horribly and in such an unfortunate fasion? You hater of truth, you user of obviously discredited creationist quackery for rhetorical effect, I shall protect my secret proofs of evolution from your evil hands! .... just saying this is what I'm feeling from you right now.

    Negative Entropy: "OK. after reading your new set of comments. I see that we would just continue in circles. So, we are done for now.

    Feel free to steer us out when you come by new evidence. Or you can always let me know what convices you if I ever gain worthiness in your sight.

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  130. John:
    ====
    Except that "dogs to whales" pretty much sums up your position. That's what makes me think that YOU GUYS are "B.S.ing" But I will clarify from now on and say doglike or Pakicetus or proto-whale so it sounds less rediculous when you defend it.
    ====

    Explain where's the B.S. in Pakicetus being related to whales, given the evidence. I guess you know a lot of comparative anatomy backing that position, don't you?

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  131. "Dogs to whales" is actually wrong. The claim is that Pakicetus is closely related to whales. Dogs and whales share ancestors, that's another claim.

    And by the way, it's not just anatomical evidence that points to a close relation between whales and other mammals (ungulates, in particular). Genetic evidence independently points that way.

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  132. John: Yeah, I thought someone might point that out, but I think it still gives a good idea of the amount of diversity that can arise. Besides, a large part of this issue seems to be how connected the paths between genes are, whether one, two, or 50 or more mutations. Are we appealing ot hopeful monsters again, or no? I'm just trying to get his whole idea so I can evaluate what he's saying.

    Point mutation is very limited. Recombination is a very powerful mechanism in evolution.

    John: I was just wondering if you thought Pakicetus gained a significant portion of it's genes from "another" organism along the way.

    Possible, but most variation is believed to have originated within closely related organisms.

    John: Unless someone has sequenced a proto whale genome from fossilized remains, I'll assume this means something like, we found a fossil that had more flipper like paws and so this must have come from genes that gradually morphed no more than 2 or 3 mutations at a time to the current form in whales.

    Start with the nested hierarchy, not an isolated lineage. There is strong evidence of Common Descent. This provides the historical context, and there are a number of well-supported evolutionary lineages.

    John: if you played the tape in reverse, you'd say it was tetrapod evolution and it had advantages because it could forage on land.

    Playing the tape in reverse, given the overall historical context, makes no sense.

    Demonstrating natural selection for historical cases can be difficult. The evidence in this case is rather straight-forward; an open niche followed by invasion and increasingly adaptive characteristics.

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  133. John,

    I am so sorry that you spent half a week on me and got no new information. But sure it must be hard for you to get new information if you are trying so hard not to get it. After all, you mistook and twisted attempts at giving you new information and got us stuck into circles of clarifying and clarifying and clarifying what should have been easier.

    and it seems like an act you're using to leave in a harumph

    Take it whichever way you like the most. I have grown up beyond kinder-garden. I can live with whatever you want to imply.

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  134. oleg:
    =====
    And by the way, it's not just anatomical evidence that points to a close relation between whales and other mammals (ungulates, in particular). Genetic evidence independently points that way.
    =====

    Of course, but I wan to know about John's specific disdain for Pakicetus. You need to use morphological data to link fossil andextant taxa before using genetic evidence.

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  136. I spent over 20 hours on these conversations so I could just spit out caricatures of evolution?

    Sure you did.

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  138. Yes it started that way, but in a very short time (relatively speaking) you had a huge amount of allele variability in the flask.

    No you didn't.

    And you're forgetting that although sexual reproduction can combine the mutations you want in the same organism, unless they already provide selectable advantage (the original issue), they are no more likely to be retained there than any other random mutation.

    But the key is whether they gave an advantage. It seems quite evident that in the whale example they did. Unless you have some piece of evidence to the contrary.

    More genes simply reduces the selection coefficient for each gene by the same factor.

    I have no idea what you are saying, but more genes increases the possibilities for recombinations and shuffling exponentially.

    As for transposons, tandem duplications, controlling sequences and regulatory proteins, these are all found in E.Coli as well, yes?

    If you think that an organism having around 90% of its DNA as genes has the same tandem duplications, transposons, and controlling sequences as an organism that has perhaps at most 5% of its DNA as genes then maybe. A much higher proportion of coding genes in multicellular eukaryotes are regulatory proteins than in E. coli, also increase exponentially the possibilities for new regulatory cascades.

    This is a very simplistic way of approaching evidence. I did not say there was NO evidence compatible with this event. If fossil A has a particular bone structure more similar to fossil B than average, the evidence is more compatible. But one piece of evidence that falsifies is worth a hundred pieces that seem to support.

    No, it is not simplistic. New genes would be a surprise, but not enough to falsify the theory. One piece of evidence that falsifies sure is worth a hundred pieces that support it. New genes show potential as falsifiers. But that's it. We would have to ask whether these genes look like virus, like transposons, like transported by either (as by being surrounded by such and such kinds of sequences), et cetera. But we don't know if there are any new genes there, do we?

    To be certain the actual history of whales will remain unaltered. But you are comparing natural selection to very strong directed selection.

    What exactly makes natural selection impossible to qualify as strong "directed" selection? (quotes because you probably charged the word with "intelligent design" overtones). A niche is a direction, competition can be strong and thus push a population strongly and away (directed), lack of food in one niche and availability of food at another can be selection forces both strong and directed, the results of natural selection over a long period can look as the results of shorter periods of stronger selection ...

    see how long your dog breeds last against even the average mutt, let alone wolves.

    See how long do the wolves last among humans. Dogs are adapted to an environment where wolves can't compete. Wolves are adapted to an environment where our dog breeds can't compete. So?

    No more time in my hands until perhaps a week. The other guys seem willing to have some fun conversing with you. Enjoy.

    ...

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  139. "And you're forgetting that although sexual reproduction can combine the mutations you want in the same organism, unless they already provide selectable advantage (the original issue), they are no more likely to be retained there than any other random mutation."

    Sorry, this is not true. There are usually two versions of each gene and it has been shown in some marine species (for example), that even fatal genes can be maintained within a population as long as this gene is recessive. In marine species this has been shown to make it possible for them to "move" inland and "change" to fresh water species in a hurry which seemed to be impossible due to the huge problem of maintaining homeostasis in freshwater vs. saltwater.

    Also, some genes are discovered that are, what is called female/male driven. That means, there are genes that are related to sex which are maintained within a population even though they are detremental to either the female or the male. Depending on the mating system however, the detremental gene is maintained within the population anyway which makes it possible for the species to change in a hurry once additional genetic changes or environmental changes eventually let that gene fall under positive selection.

    With those and other known systems it is possible that a gene (and with this a protein) can change (slowly) even through stages in which they are fatal to the animal and still will be maintained within a population until some additional changes in the environment or further genetic changes turn out to be advanterous.

    It is true that it is almost impossible for proteins to have evolved at once because of their usually complex function and sensitivity to changes. However, the model that everything has to happen at once is false.

    There are mechanism that allow maintaining even fatal genes (silently) within a population and with this allows the accummulation of changes until the summation of all those changes eventually turns out to be advanterous. Once such accumulation of change is advanterous and therefore then selected for, a large population can "pop up" in a hurry without any problem. Not possible? Well.

    For this, see what happened with introduced species. There are cases in modern times (we saw it happen) where the introduction of only a couple of individuals that had advanterous trades was enough for to end up with a high population within only a few decades.

    Biology is tricky which isn't a surprise because guess what, those mechanisms that allow such (seemingly impossible) things are under extreme positive selection.

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  140. Oh, sorry I forgot another three major mechanism by which genes are maintained even though they might not be optimal or even "dysfunctional".

    First, genes are linked. That means the chance of recombination is dependent on the distance between the genes on a chromosome. As closer they are, as less likely recombination happens.

    Now, lets say there is a gene that is under high selective pressure like one that is related to good eye sight. Directly next to it is another gene, lets say something that has to do with locomotion. If the locomotion gene gets mutated it still will be maintained within the population if the eye sight gene is under ligher selective pressure than the locomotion gene. This way, the "defective" locomotion gene will be maintained.

    It might get mutated again and again and again or the environment changes - whatever. As long as it is carried along with the eye sight gene due to its selective pressure, it will be maintained even if it is somewhat dysfunctional. At some point it then might become highly advanterous due to some "good" mutation or due to environmental changes and BANG, there we go.

    Second, there are many examples where things are just "good enough" instead of optimal. It seems to be that "good enough" is enough to be maintained. With this, genes can "move" through dips within the fitness landscape without any problem.

    Third not every gene is always under selective pressure. Some just are not and it is sort of random what happens to those genes. They can change without any problem within reasonable limits because it just doesn't matter. At some point it might get under selective pressure and there we then get a "large" change that seemingly came out of nowhere.

    So, accumuation of small "disadvanterous" changes that lead as a summation to an highly advanterous large change impossible? NO, realy not.

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  141. Hey emil,

    You misread John a little bit. He is aware that there can be random conservation and recombination of non-advantageous alleles (neutral and semi-neutral, and he might love the idea of disadvantageous). But his "point" (semi-inpired by Neal's) is that whales could not have evolved because they needed many mutations that all by themselves provided no advantage. Well, he might have a "might" there somewhere. So, my answer is that I don't see why whale evolution would have "needed" the accumulation of many mutations that in and on themselves were neutral, and only combined would have helped the changes. He is B.S.ing the case of whale evolution based on the citrate thing in E. coli having needed two mutations that each is neutral without the other.

    By the way, I enjoy your posts (I suspect that English is not your first language though).
    Best!

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  142. Correct English is not my first language. Usually I find the mistakes after I posted it and think: OH, I am such an idiot. I should know how to do better....

    Sorry for the whale thing and any confusion I caused. I don't read it all. It is too much to read and there are too many other things I have to take care of.

    Certainly we don't "need" the accumulation of neutral mutations for evolution to happen. Well, it can speed it up quite a bit though...:)

    I don't know but somehow I have the feeling that those who argue pro creation don't really believe it and just argue for the "fun" of it because it doesn't make any sense. I might be wrong though.

    However there are actually people who do believe all this and some of them are very young and believe it so strongly that they reject any other idea from the beginning, making science education impossible in high school.

    It is scary and causes quite some teacher huge trouble because those kids convert the Biology class into nothing else than a destructive debate that (supposed to?) goes nowhere - naturally.

    It is amazing.... I could never believe it if I would not witness it. It is really sad because not all kids are lucky and have a scientist as parent who can make up for the loss of time spend on debates - and there it goes the science education in high school all together, while higher education is crying about the decreased number of young people interested in studying it, which in return has the result that there might not be enough people in near future to advance our knowledge - at least in the US. And, this is no fun at all. And - I am in a state that "only" has moderate problems with this issue..... I don't even want to know how it is at other places.... Why are we doing all this to ourselves?

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