Intelligent Design

Rescue Proteins Leave Evolutionists In The Ditch

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Put intuition aside for a moment and imagine a scenario where E.coli knockout strains that have been deleted for conditionally essential genes are rescued by proteins taken from a protein library composed of >106 de novo designed sequences.  The prevailing assumption- that functional proteins are constrained to a very small subset of possible sequences- would lead us to infer that finding them by a random search through sequence space would be tantamount to impossible.  But a PLOS One paper published in early 2011 appears on the surface to have given us much room for thought.  Scientists from Princeton’s Department of Chemistry and Molecular Biology used a combinatorial library of 102-residue long proteins to rescue non-viable E.coli knockouts.   The functional losses in the knockout strains affected serine, glutamate and isoleucine biosynthesis and disabled the cells’ natural capacity for iron acquisition in iron-limited environments.

The E.coli knockouts were auxotrophic meaning that they exhibited a failure to grow on minimal (M9-glucose) media even after several weeks of incubation.  But following transformation with the combinatorial library, several cases of successful colony growth were documented suggesting that the certain genes contained therein had successfully complemented the deletions.  Sequence comparisons through formal BLAST searches showed that the rescue proteins involved, eighteen in all, were unlike any protein found in nature.

Truth be told these rescue proteins were not entirely random.  Their sequences had been engineered to ensure that they would fold into a stable 3-D structure.  And not just any structure.   Molecular biologists are well aware that canonical sequence rules exist that must be adhered to if they are to maximize the chances of proteins folding correctly.  In an alpha-helical fold, for example, polar and non-polar residues must be carefully ordered to make certain that the hydrophilic (‘water-loving’) and hydrophobic (‘water-hating’) faces of the fold emerge.  The Princeton group adopted a binary code strategy of polar and non-polar residues to get 1.5x10exp6 four-helix bundles.  In this singularly fundamental aspect they were designed.  

What was the molecular basis that allowed rescue?  From their own experiments the Princeton group ruled out the likely hood that novel pathways that bypass the adverse effects of the knockout genes had arisen since E.coli mutants that were deficient in other steps of the naturally occurring biosynthetic pathways could not be rescued.  Also dismissed was the interpretation that “global alterations in metabolism had been induced by the mere expression of foreign genes” (a stress response of some kind) since none of the eighteen rescue proteins appeared to have been unfolded- a tell-tale symptom of such a global response.  Mutations that minimally disrupted their structure abolished their rescue capabilities. 

The evidence seemed compelling.  These de novo sequences were exerting specific functional effects that served to avert an otherwise fatal outcome for their bacterial hosts.  Still the ‘design’ point-of-departure raised above was without question central to this particular success story.  In his book Signature In The Cell Stephen Meyer has noted how it is sequence specificity that ensures that amino acid chains fold into “useful shapes or conformations” (Ref 1).  Without a library tailored for the formation of four-helix bundles, the Princeton study is unlikely to have yielded anything that would come close to salvaging the debilitated bacteria.   To make matters worse, this study failed to consider in detail the cooperativity that so evidently characterizes the organismic molecular scheme.  What we see here is akin to taking one piece out of a jigsaw puzzle and finding another to put in its place albeit with some considerable force of fit.  Those who espouse blind evolution are still left reeling over how to explain the origin of the entire puzzle.

Importantly cells transformed with rescue proteins exhibited growth that was “significantly slower than those expressing the natural protein” (the non-knockout strains).  Exponential growth occurred 24-144 hours later and reached culture densities that in some cases were as low as 12-15% of wild-type.  The authors readily admit that the library proteins may “function by different mechanisms than the natural proteins they replace”.  Indeed assays designed to test for the deleted functions failed to show that the de novo sequences exhibited comparable enzymatic activities.  The evolutionary inference given by the authors- that billions of years of evolution have driven optimal activities for faster growth- therefore appears to be nothing more than a rehash of a positively stale Darwinian fairytale.  After all, if the proteins function by different mechanisms, one cannot allege that they are in any sense on the way to becoming the more efficient naturally occurring protein entities we observe in E.coli today.

For the full PLOS One article see:
Michael A. Fisher, Kara L. McKinley, Luke H. Bradley, Sara R. Viola, Michael H. Hecht (2011)  De Novo Designed Proteins from a Library of Artificial Sequences Function in Escherichia Coli and Enable Cell Growth, See http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015364

Further Reading
1.     Stephen Meyer (2009) Signature In The Cell: DNA And The Evidence For Intelligent Design, Harper Collins Publishers, New York, p.99

7 Replies to “Rescue Proteins Leave Evolutionists In The Ditch

  1. 1
    bornagain77 says:

    semi-OT; though the ‘probability argument’ has long been a staple of the design argument, it seems to me that a more forceful argument for ID is in the works. Please note in the last part of this video,,,

    Quantum Information/Entanglement In DNA & Protein Folding – short video
    http://www.metacafe.com/watch/5936605/

    ,,, where ‘Gretchen’ asks the biologists to test to see if ‘quantum information/entanglement’ is at play in protein folding. And it occurred to me this morning that there is already solid evidence that quantum information/entanglement is at play in determining the structure of proteins,,,

    Proteins with cruise control provide new perspective:
    “A mathematical analysis of the experiments showed that the proteins themselves acted to correct any imbalance imposed on them through artificial mutations and restored the chain to working order.”
    http://www.princeton.edu/main/...../60/95O56/

    Cruise Control permeating the whole of the protein structure??? This is an absolutely fascinating discovery. The equations of calculus involved in achieving even a simple process control loop, such as a dynamic cruise control loop, are very complex. In fact it seems readily apparent to me that highly advanced mathematical information must reside along the entirety of the protein structure, in order to achieve such control. This fact gives us clear evidence that there is far more functional information residing in proteins than meets the eye. Moreover this ‘oneness’ of cruise control, within the protein structure, can only be achieved through quantum computation/entanglement principles, and is inexplicable to the reductive materialistic approach of neo-Darwinism!

    But what makes this fundamentally different from the probability argument, that has been used against neo-Darwinists thus far, is that quantum entanglement itself is what was used by Alain Aspect and company to falsify ‘local realism/reductive materialism’ in the first place;

    The Failure Of Local Realism – Materialism – Alain Aspect – video
    http://www.metacafe.com/w/4744145

    The falsification for local realism (reductive materialism) was recently greatly strengthened:

    Physicists close two loopholes while violating local realism – November 2010
    Excerpt: The latest test in quantum mechanics provides even stronger support than before for the view that nature violates local realism and is thus in contradiction with a classical worldview.
    http://www.physorg.com/news/20.....alism.html

    ,,,,It is very interesting that quantum entanglement should be found in molecular biology, for how can entanglement, in biology, possibly be explained by the materialistic framework of neo-Darwinism when Alain Aspect and company falsified the validity of local realism (reductive materialism) in the first place with quantum entanglement? It is simply ludicrous to appeal to the materialistic framework, which undergirds neo-Darwinism, that has been falsified by the very same quantum effect you are seeking to explain! Probabilities simply do not apply in trying to explain entanglement in biology since it is shown to be impossible for quantum entanglement to be explained by the materialistic framework in the first place!!!

    further note;

    Quantum states in proteins and protein assemblies: The essence of life? – STUART HAMEROFF, JACK TUSZYNSKI
    Excerpt; Activities in living cells are performed by protein conformational dynamics which in turn are governed by quantum
    mechanical van der Waals London forces in intra-protein “hydrophobic” pockets.,,, The unitary oneness and ineffability of living systems may depend on mesoscopic/macroscopic
    quantum states in protoplasm.
    http://www.valdostamuseum.org/.....rotein.pdf

  2. 2
    Petrushka says:

    The point of the paper would be that functional sequences are rather common, even in sequences that bear no resemblence to “naturally” occurring sequences.

    We have demonstrated that sequences designed de novo can provide functions necessary to sustain the growth of living cells. It should be emphasized that these macromolecules were isolated with relatively high frequency from a collection of sequences that were designed to adopt a stable globular fold, but were not explicitly designed for function.

    Both in terms of linear sequence and 3-dimensional structure, the novel proteins differ substantially from the natural proteins they replace: The binary patterned sequences in Figure 3 show no significant sequence similarity to any known proteins.

    It’s a statement about how isolated the islands of function are, and how rare.

  3. 3
    tragic mishap says:

    Interesting.

    What they are probably aiming at is the type of non-Darwinian co-option of the kind that is used to argue against irreducible complexity. I would have to say I’m impressed. I would not have expected what they did could have a measurable effect.

    But as you say, there’s no way they performed 20^102 transformations. The problem is intractable without recourse to intelligent design.

  4. 4
    Petrushka says:

    But as you say, there’s no way they performed 20^102 transformations. The problem is intractable without recourse to intelligent design.

    Of course not. What the paper is arguing is that sequence space is full of synonyms and near synonyms.

  5. 5
    tragic mishap says:

    Again, interesting paper.

    A lot of these types of things end up as membrane spanning proteins. T-urf13 and PfCRT are examples. And of course alpha helixes usually end up in the membrane.

    PfCRT apparently causes a leak in the membrane which allowed something to go where it couldn’t go before. Same thing with T-urf13. It’s possible that there are other proteins in the cell capable of performing those reactions at very slow rates that do not show up in the suppressor study they referenced because they can’t get through the right membranes.

  6. 6
    tragic mishap says:

    Of course not. What the paper is arguing is that sequence space is full of synonyms and near synonyms.

    So this would be a great time to keep growing these transformed bugs to see how much their fitness can increase.

  7. 7
    Petrushka says:

    So this would be a great time to keep growing these transformed bugs to see how much their fitness can increase.

    Good idea. Probably being planned. But would require time, like the Lenski experiment.

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