Wednesday, January 27, 2010

Prestin and Darwin's Gardener

A fundamental, and often false, prediction of evolution is that functionally unconstrained DNA should not be conserved in distant species. As described here, everything from proteins to long stretches of DNA, though highly similar across different species, defy evolutionsts who search for a functional constraint, as required by their theory. And how do evolutionists respond? They claim that the mystery DNA must have a function, even though myriad tests have found none. If we cannot detect the function, then there must be a problem with the tests. There must be a function which otherwise is undetectable to us. It is a perfect example of how religious belief resists falsification as Antony Flew once illustrated in his gardener parable:

Once upon a time two explorers came upon a clearing in the jungle. In the clearing were growing many flowers and many weeds. One explorer says, "Some gardener must tend this plot." The other disagrees, "There is no gardener." So they pitch their tents and set a watch. No gardener is ever seen. "But perhaps he is an invisible gardener." So they set up a barbed-wire fence. They electrify it. They patrol with bloodhounds. (For they remember how H. G. Well's The Invisible Man could be both smelt and touched though he could not be seen.) But no shrieks ever suggest that some intruder has received a shock. No movements of the wire ever betray an invisible climber. The bloodhounds never give cry. Yet still the Believer is not convinced. "But there is a gardener, invisible, intangible, insensible, to electric shocks, a gardener who has no scent and makes no sound, a gardener who comes secretly to look after the garden which he loves." At last the Sceptic despairs, "But what remains of your original assertion? Just how does what you call an invisible, intangible, eternally elusive gardener differ from an imaginary gardener or even from no gardener at all?"

Darwin and the evolutionists see a gardener, and to these motivated believers evolution is true despite even glaring question marks and failed expectations that have other observers wondering how evolutionists can be so sure their idea is a fact. And as in Flew's parable, sometimes evolutionists have creative explanations for why the evidence does not seem to reveal their gardener.

Consider prestin, a protein important in mammalian hearing. Prestin, a transmembrane protein in the outer hair cells of the cochlea, is a frequency-selective amplifier in a sound system that works something like this.

As sound enters the ear, it deflects the outer hair causing tiny amounts of stretching or compression in the outer hair cells. There are channel proteins that sit in the membrane of these cells which are sensitive to such mechanical strain. These proteins provide a tunnel (or channel) across the membrane so that ions can easily cross, and the mechanical strain can cause the channels to open.

These channels are precisely designed to allow only certain types of ions to cross. For example, some channels allow the positively charged potassium ion to cross but not the positively charged sodium ion, and vice-versa.

When a channel opens, ions usually tend to cross through the membrane (either into the cell or out of the cell) because the ion concentration is not uniform, and because there is a voltage, across the membrane. Such differences in concentrations across the membrane, and the voltage, are actively maintained by the cell. They serve as a sort of battery whose energy can be tapped at any time by opening membrane channels.

When the incoming sound causes certain channels to open, the ions that cross cause a change in the membrane voltage. In the outer hair cells, this voltage change encourages negatively charged chlorine ions to exit the cell. They interact with the prestin protein, in the membrane, to cause a mechanical deformation resulting in the elongation of the cell.

In other words, the incoming sound, that caused the hair to move, ends up causing yet more hair movement, and this serves precisely to amplify the incoming sound. This amplification is greater at low sound levels, as it should be.

One of the interesting features of this system is the speed at which it operates. Obviously in order to amplify sound you need to respond as fast as the changes in sound occur. Protein motors often use chemical energy (such as the splitting of the ATP molecule) but that would be too slow for the ear's sound system. Instead, prestin uses the membrane's voltage. This electrical energy can be used much faster and prestin operates at microsecond rates. Here is how one paper summarized the system:

The exquisitely high sensitivity and frequency selectivity of the mammalian hearing organ originates from a mechanical amplification mechanism that resides in the organ of Corti, the sense organ of hearing in mammals. The gain provided by this amplification can reach as high as a thousandfold; it is highest at low sound levels and progressively diminishes with increasing sound energy.

Of course evolution has no explanation for the origin of this system beyond unfounded speculation, but that is no surprise. New research is, however, adding a twist to the story.

We now know that prestin proteins in certain bat and whale species (used in their biosonar systems) are more similar than evolution would expect. The massive prestin protein has too many amino acids that match up between these species. If one were to construct an evolutionary tree on the basis of prestin comparisons alone, then the bat and whale would be grouped together, and that cannot be correct.

This fact alone need not be a problem for evolutionists. They simply say that prestin is under the influence of strong selection. In other words, there are strong functional constraints on prestin that require more similarity, even between distant species, than we typically find in proteins.

In particular, researchers identified nine amino acids in prestin that seem to be responsible for the overly-consistent whale-bat matchup. Those nine amino acids must be under very strong selection. If one of them mutated then the biosonar system would not work well. The bat or whale would not survive, and that is why we don't observe such changes. That is how natural selection works.

But if all nine amino acids are required, how did evolution stumble onto the design in the first place? It would be highly unlikely for the right nine amino acids to arise via blind mutations, at the same time.

Of course this conundrum is not confined to the prestin protein. Biology is packed with incredible designs that appear to be finely-tuned. And dozens of finely-tuned design parameters do not appear to be the result of evolution.

The typical evolutionary explanation for biology's wonders is that those design parameters evolved one at a time. It was a gradual process as each setting independently contributed to increased fitness. In other words, a long series of lesser designs preceded today's marvels.

But if a lesser design was good enough before, then why is it not good enough today? Why are those nine amino acids maintained today in prestin if before only a few were required for success?

The evolutionary answer is that there was an arms race. Yes, lesser designs did the job before, but that was then and this is now. The competition has improved and so what worked before no longer does the job.

But like Flew's gardener, these other worlds are forever up for speculation. The competition may or may not have had this or that capability at this or that particular time. The precise timings and interactions can always be tweaked to fit the evolutionary narrative.

And if it turns out that prestin is not so sensitive to some of those nine amino acids, evolutionists won't skip a beat as they didn't before when conserved designs were found to lack the expected sensitivities. One way or another, there is a gardener. Religion drives science, and it matters.

15 comments:

  1. ~~~~~~~~~~~~~~~~~~
    If we cannot detect the function, then there must be a problem with the tests. There must be a function which otherwise is undetectable to us.
    ~~~~~~~~~~~~~~~~~~

    Could we call this evolution of the gaps?

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  2. Cornelius -

    Wow. Well that all sounds very impressive and sciencey, doesn't it?

    But I'm afraid I'm going to ahve to repeat my question from the previous thread: 'So what?'

    Assuming you are correct that evolution is unable to account for this (and again, I don't know enough biology to judge), you are merely showing that there are mysteries in biology.

    Which is a point no-one is disputing.

    You are certainly not showing that religion drives science.

    It may not seem so to you, who keeps focussing on specific biological points which are either not fully understood, or just not fully understood BY YOU, but the theory of evolution is built on a vast deal of positive evidence. Bearing that in mind, it is not religious to use it as a working hypothesis to explain what biological mysteries remain.

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  3. Cornelius Hunter: Darwin and the evolutionists see a gardener ...

    Don't you have the analogy backwards? It's supposed to be the theist who believes in the invisible gardner.

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  4. Zachriel -

    THANK YOU!!!

    I was totally thinking the same thing. Surely this invisible, unfalsifiable gardner is a metaphor for an invisible unfalsifiable God!

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  5. Perhaps it's worth noting that bat and whale do not group together in an evolutionary tree constructed from the prestin gene's synonymous nucleotide substitutions. Only when the prestin gene's nonsynonymous nucleotide substitutions (or the amino acid substitutions those cause) are used to construct the tree does one find certain bats grouped with certain whales. So, there's a clear history of evolutionary relationships recorded in the DNA's synonymous substitutions, which are relatively unconstrained by function, and a clear history of adaptive selection for gradually improving biosonar in the DNA's nonsynonymous substitutions. Convergent and parallel evolution both happen; those aren't just theory-saving, special-pleading exceptions to diversifying evolution. If you read the actual papers in Current Biology, the prestin gene data are very compelling. I fail to see what the prestin story has to do with faith-based "gardeners."

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  6. cfauster:

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    Perhaps it's worth noting that bat and whale do not group together in an evolutionary tree constructed from the prestin gene's synonymous nucleotide substitutions. ... So, there's a clear history of evolutionary relationships recorded in the DNA's synonymous substitutions, which are relatively unconstrained by function,
    ---

    Keyword: "relatively." Evolution predicted synonymous mutations had no impact on function or fitness. That, of course, turned out to be false. But if they are functional, then this spoils their story of how those meaningless swaps reveal evolutionary relationships. So they say "relatively" to have it both ways. Yes, the evidence is they have some function, but it is minor and can be discounted for our purposes. Nothing like underdetermined theories.


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    and a clear history of adaptive selection for gradually improving biosonar in the DNA's nonsynonymous substitutions.
    ----

    Actually there is no such "clear history." Beyond speculation, we have no detailed pathway of prestin evolution and evolution of the hearing system it works in.


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    If you read the actual papers in Current Biology, the prestin gene data are very compelling. I fail to see what the prestin story has to do with faith-based "gardeners."
    ----

    In fact the prestin gene data are not "very compelling." Significance sequence identity in long separated lineages, with no evidence of constraint aside from "there must be constraint because we know evolution is true", is not "very compelling." They are "very compelling" only to those who already believe evolution is a fact. That evolutionists view this as "very compelling" is yet another example of evolution's anti intellectualism. Evolutionists are unable to step out of their beliefs, and provide theory-neutral evaluations.

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  7. Mr. Hunter:

    1) "Evolution" did not "predict that synonymous mutations had no impact on function or fitness." And what is this business about wanting to "have it both ways"? Do you not understand, or do you not accept, the difference between synonymous and nonsynonymous nucleotide substitutions? Do you not understand why, based on molecular biology, we expect that synonymous substitutions may have some impact on function or fitness via codon frequency and RNA structure effects, but not as much impact as nonsynomymous substitutions that result in amino acid substitutions with very different R groups chemistries, especially in sites critical for protein function? Do you think it has to be all or nothing, with no quantitative degrees of impact?

    2) Are you aware of what happens when prestin is mutated at some of the critical amino acids in rodents? Do you think we have no independent evidence that any of those nine amino acids are important?

    3) Please provide your own theory-neutral evaluation of the data, but only if you deal with the data. So far, it looks like you have not read the Current Biology papers. Ask Michael Behe to help. On questions like this one, he usually deals with the data pretty objectively.

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  8. cfauster:

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    1) "Evolution" did not "predict that synonymous mutations had no impact on function or fitness."
    =====

    I see. And did we go to the moon? This assertion is so absurd one hardly knows how to respond. Evolutionists believe life just happened to show up on the scene and biology is a fluke. When we discovered that, in protein-coding genes, some mutations don't alter the protein sequence (ie, synonymous mutations), evolutionists naturally assumed they are meaningless and have no effect on fitness. After all, biology is a fluke and there can't be anything clever here.

    So they used the inferred ratio of non synonymous to synonymous mutations as an indicator of selection on the gene. Now they deny they ever thought that.

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  9. Evolutionary theory makes two simple predictions in the context of our discussion:

    1) Mutations that make relatively little difference in function ("function" including not only the performance of gene products but also the efficiency of maintaining and expressing the DNA) will serve as better indicators of phylogenetic history.

    2) Mutations that make relatively big differences in function (again, broadly define) will serve as better indicators of positive or negative selection, for adapative changes or against maladaptive changes.

    An analogy might be this. If you want to know about the history of meteor impacts in our region of our solar system, the moon's surface provides a better record than does the earth's surface. But if you want to study what active geological, atmospheric, hydronomic, etc. forces can do to the surface of a planet, then the earth is the place to look.

    When the near-universal (canonical) genetic code was discovered, its redundancy means that most amino acids (18 of the 20 typically used in proteins) are specified by multiple synonymous codons. If one is considering only protein amino acid sequence then yes, molecular biology (not evolution) originally predicted that mutations substituting one synonymous codon for another would have no effect.

    Notice how evolutionary theory suggested a test for whether there might be other effects beyond amino acid sequence. It was the evolutionary biologists who alerted the molecular and cellular biologists to look for phenotypic effects in some cases of synonymous nucleotide substitutions.

    I need to add one more thing, Mr. Hunter. I am more sympathetic to some of your views than you probably suspect. For example, my concept of God's action in the world certainly allows for guidance of both human and natural history. And I appreciate many things about Michael Behe's work. He and I part company over technical matters and, more fundamentally, over our differing understandings of scientific data's utility in revealing intelligent design by a completely unspecified, unconstrained designer.

    I appreciate that a lot of the best science has been done by scientists motivated to understand the world as the work of the Creator. A lot of the best science has also been done by scientists motivated to show that God (who they don't believe exists) "didn't do it." Fortunately, good science can be done regardless of the extra-scientific motivations.

    I just wanted people to know that gene sequences, including even the prestin gene sequence, provide a lot more information when one considers the distinction between synonymous and nonsynonymous nucleotide substitutions. The Science Daily-type reviews of the work published in Current Biology don't tell the whole story, and that's appropriate. But your original post implied that an evolutionary approach to the relationships between prestin genes in various species would be nothing more than yet another display of evolutionists altering their theory to accommodate challenging data. No, Mr. Hunter, it's much more than that. But I think you should consider teaming up with a molecular biologist such as Michael Behe who could help you understand that, in the case of prestin and many other genes as well as nongenic DNA, nucleotide sequence comparisons do provide valuable information for inferring both phylogenetic history and the relative functional importance of various mutations.

    Best wishes.

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  10. cfauster:

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    So, there's a clear history of evolutionary relationships recorded in the DNA's synonymous substitutions, which are relatively unconstrained by function, and a clear history of adaptive selection for gradually improving biosonar in the DNA's nonsynonymous substitutions.
    =======

    "Clear history" can mean different things. If you're saying there are some successful predictions here, then sure.


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    Convergent and parallel evolution both happen ...
    =======

    So here we have a bigger claim. This is not a fact, as you suggest. The *fact* is that this evolutionary certainty cannot be arrived at from the data.



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    If you read the actual papers in Current Biology, the prestin gene data are very compelling.
    =======

    Sure, from an evolutionary perspective.



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    If you read the actual papers in Current Biology, the prestin gene data are very compelling. I fail to see what the prestin story has to do with faith-based "gardeners."
    =======

    Because it depends on the assumption that there is a gradual build-up of capability which, at least for now, cannot be disproved. Imagine if mutagenesis studies were to find that sequence variations, of those key residues, resulted in failure of some sort. That would be a problem because it would mean a gradual build-up is unlikely. OTH, imagine if mutagenesis studies were to find that sequence variations, of those key residues, resulted in very little change in function. That would be a problem because it would render the strong sequence conservation difficult to rationalize. But in either case I guarantee evolution would not skip a beat. No one would be questioning the evolution of prestin. I can guarantee this because it has already occurred in other examples.




    =======
    Do you not understand, or do you not accept, the difference between synonymous and nonsynonymous nucleotide substitutions? Do you not understand why, based on molecular biology, we expect that synonymous substitutions may have some impact on function or fitness via codon frequency and RNA structure effects, but not as much impact as nonsynomymous substitutions that result in amino acid substitutions with very different R groups chemistries, especially in sites critical for protein function? Do you think it has to be all or nothing, with no quantitative degrees of impact?
    =======

    Sure, that all makes sense. OTH, since the synonymous substitutions do make a difference, it is also possible that the patterns of similarity and differences we see have functional reasons.


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    Are you aware of what happens when prestin is mutated at some of the critical amino acids in rodents? Do you think we have no independent evidence that any of those nine amino acids are important?
    =======

    I haven't see that. Perhaps you can share this.

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  11. cfauster:

    =======
    Evolutionary theory makes two simple predictions in the context of our discussion:

    1) Mutations that make relatively little difference in function ("function" including not only the performance of gene products but also the efficiency of maintaining and expressing the DNA) will serve as better indicators of phylogenetic history.
    =======

    So do ultra-conserved elements falsify this prediction?



    =======
    When the near-universal (canonical) genetic code was discovered, its redundancy means that most amino acids (18 of the 20 typically used in proteins) are specified by multiple synonymous codons. If one is considering only protein amino acid sequence then yes, molecular biology (not evolution) originally predicted that mutations substituting one synonymous codon for another would have no effect.
    =======

    But of course evolutionists do not merely consider protein amino acid sequence. They consider overall fitness.



    =======
    I just wanted people to know that gene sequences, including even the prestin gene sequence, provide a lot more information when one considers the distinction between synonymous and nonsynonymous nucleotide substitutions.
    =======

    Agreed.



    =======
    But your original post implied that an evolutionary approach to the relationships between prestin genes in various species would be nothing more than yet another display of evolutionists altering their theory to accommodate challenging data. No, Mr. Hunter, it's much more than that.
    =======

    The post was about (i) the complexity of mammalian hearing and prestin, and (ii) the strikingly conserved residues. It was not an exhaustive look at all the data. You seem to think the synonymous alignments mandates an evolutionary explanation (which is false), and therefore my omission of those data is grevious.




    =======
    But I think you should consider teaming up with a molecular biologist such as Michael Behe who could help you understand that, in the case of prestin and many other genes as well as nongenic DNA, nucleotide sequence comparisons do provide valuable information for inferring both phylogenetic history and the relative functional importance of various mutations.
    =======

    Do ORFans and ultra-conserved elements count?

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  12. Yes, ultraconserved elements (UCEs) and ORFans are good examples of how genome comparisons identify interesting avenues of research.

    Regarding UCEs, I recommend a review by Baira et al. published in 2008: "Ultraconserved elements: genomics, function, and disease." RNA Biology Volume 5, pages 132-134.

    Regarding open reading frames (ORFs) that do not have identified conterparts in the genomes of other genera (hence the name "ORFans"), the interesting avenues of research are obviously different than for genes with identified homologs in other genera. As with any ORF, one wants to find out if an ORFan really is a gene and, if so, what the gene product does. And in the case of an ORFan, if it does turn out to be a gene, it might be an especially good case for asking how the gene was acquired. As an example, I recommend a report by Heinen et al. published in 2009: "Emergence of a new gene from an intergenic region." Current Biology Volume 19, pages 1527-1531.

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  13. I apologize for not carefully reading your previous request for the prestin mutation data from mice. The reference is:

    Dallos (2008) Cochlear amplification, outer hair cells and prestin. Curr. Opin. Neurobiol. Vol. 18, pages 370-376.

    On a more general note, I can't tell whether you feel that evolution makes no predictions or rather that evolution makes predictions that fail.

    Take histone H4 as an example. My position is that its conservation predicts, according to evoltionary theory, that changes in H4 amino acid sequence will usually cause phenotypic effects. That's been tested in yeast. In various posts you claim that such effects have not been observed. Now Michael Behe's work was very good, and I'm always amazed how people remain unaware of his work, essentially repeat his experiment, and are surprised to learn that many changes in H4 are non-lethal. However, a mutant can be viable (not die) but still have problems. H4 is the most conserved of the histones, and as expected, changes in its amino acids are most likely to cause phenotypic effects.
    Here the latest data as analyzed by Huang et al. (2009) in Genome Research, Volume 19, pages 674-681 in their article entitled "HistoneHits: a
    database for histone mutations and their phenotypes":
    * between yeast and humans, H4 is 92% conserved at the amino acid level
    * 87% (89 out of 102) of the amino acids in H4 show some detectable
    phenotypic effect if altered by mutation
    * in contrast, for a less conserved core histone such as H2B, only 26 of the 112 tested amino acids have so far shown a phenotypic effect
    when altered (H2B has 130 amino acids in yeast, but 8 have yet to be tested)
    * mutations of the most conserved amino acids are 2.8 times more likely to give phenotypes than mutations of the least conserved amino acids

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  14. cfauster:

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    On a more general note, I can't tell whether you feel that evolution makes no predictions or rather that evolution makes predictions that fail.
    ======

    The latter. You can check out:

    http://www.darwinspredictions.com/

    ReplyDelete