DNA Repair Proteins: Efficiently Finding Genome Errors

_{Cornelius Hunter

March 15, 2010

Intelligent Design}

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The heroics of the cell’s DNA repair system are well known, but new research is adding yet another incredible facet to the story. Experimentalists tagged DNA repair proteins with nanocrystals that light up. They then observed how they interact with DNA molecules. As reported: Read more

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Apollos@64 Thanks very clearly stated.andrewjg_{March 16, 2010
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Re#64: You say that the Szostak lab has defined functional information. Not that anybody has actually produced the functional information of complex biological systems, but that is besides the point. You seem to indicate that there is a connection of this type of 'functional information' to quantifying 'Irreducible Complexity'. I personally don't see the connection. Could you explain so that we can once and for all have an objective way to defining and assigning 'Irreducible Complexity'?hrun0815_{March 16, 2010
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Factual support- Every time we have observed proof-reading and error-correction there has always been an agency involved. What else do you need?
That is your factual support? We have error correction by humans and not by humans. Of one we know that it requires human-mental processes. Of the other, we don't know. So you simply assume that because in one agency is involved, it must also be true for the other? That's not factual support. That's simply another assertion of the same fact.hrun0815_{March 16, 2010
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BA77, to the first sentence of your [64], Zachriel replies:
No. The Functional Information in the paper has nothing to do with Irreducible Complexity, but "Functional Information as a Measure of System Complexity." The measure is dependent on the function x being considered, and a minimum specified degree of function Ex. A certain fraction F(Ex) will have the minimum specified degree of function, yielding the Functional Information -log2F(Ex). So a highly complex structure that has a function y may have zero (or undefined) Functional Information for function x. And everything has zero Functional Information if the minimum specified degree of function is zero. In other words, the measure, being highly dependent on the assumptions, is not an unambiguous metric.
David Kellogg_{March 16, 2010
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Biological Clock Excerpt: The high-resolution structures of these proteins suggest a ratcheting mechanism by which the KaiABC oscillator ticks unidirectionally. This posttranslational oscillator may interact with transcriptional and translational feedback loops to generate the emergent circadian behavior in vivo.bornagain77_{March 16, 2010
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Paley’s Watch Found in Bacteria The conjunction of structural, biophysical, and biochemical approaches to this system reveals molecular mechanisms of biological timekeeping. http://creationsafaris.com/crev200810.htm#20081031abornagain77_{March 16, 2010
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Biological clocks are evidence that clocks are an emergent property of chemistry and physics... ;)Joseph_{March 16, 2010
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Apollos- Obviously you have never heard of the "biological clock"... heh-hehJoseph_{March 16, 2010
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Joseph, actually I'm saying that clocks are an emergent property of agency. :DApollos_{March 16, 2010
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PaulN:
The fact that knowledge of what to correct and how to correct it are necessarily required to actually carry out correction is damn near axiomatic.
What if one doesn't understand the meaning of "axiomatic"? :)Joseph_{March 16, 2010
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Apollos- Are you trying to say that clocks are supernaturally Created? :)Joseph_{March 16, 2010
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hrun0815:
And nowhere is their factual support, positive or negative claim.
Factual support- Every time we have observed proof-reading and error-correction there has always been an agency involved. What else do you need? Are you kind of person who thinks the Sun might "rise" in the West tomorrow?Joseph_{March 16, 2010
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Pan Narrans:
What I’m hearing, and please correct me if I’m misconstruing your position, is that biologists and biochemists have discovered a wide variety of repair mechanisms that use pretty well understood chemistry and physics to fix certain kinds of errors that occur when DNA replicates.
Except they haven't done that. Ya see there isn't anything at all that demonstrates living organisms are reducible to chemistry and physics.
If you have real support for your positions I would be very interested to hear it.
Other than the fact that every time we observe proof-reading and error correction an agency is involved? That is enough for rational people. If all you have is the thing being discussed as evidence for a mechanism for the thing being discussed, then you are not rational. I am sure that spellchecker does not violate any laws of physics- IOW it procedes via understood physics. Does that mean it is a blind, undirected process? And why can't you find any support for your position- that blind molecules can correct errors- outside of biology? I find that lack of support very telling. And as if you can use the thing being debated as supporting your side of the debate- talk about circular...Joseph_{March 16, 2010
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It has now been demonstrated Irreducible Complexity can be mathematically quantified as functional information bits(Fits). Functional information and the emergence of bio-complexity: Robert M. Hazen, Patrick L. Griffin, James M. Carothers, and Jack W. Szostak: Abstract: Complex emergent systems of many interacting components, including complex biological systems, have the potential to perform quantifiable functions. Accordingly, we define 'functional information,' I(Ex), as a measure of system complexity. For a given system and function, x (e.g., a folded RNA sequence that binds to GTP), and degree of function, Ex (e.g., the RNA-GTP binding energy), I(Ex)= -log2 [F(Ex)], where F(Ex) is the fraction of all possible configurations of the system that possess a degree of function > Ex. Functional information, which we illustrate with letter sequences, artificial life, and biopolymers, thus represents the probability that an arbitrary configuration of a system will achieve a specific function to a specified degree. In each case we observe evidence for several distinct solutions with different maximum degrees of function, features that lead to steps in plots of information versus degree of functions. http://genetics.mgh.harvard.edu/szostakweb/publications/Szostak_pdfs/Hazen_etal_PNAS_2007.pdf Mathematically Defining Functional Information In Molecular Biology - Kirk Durston - short video http://www.metacafe.com/watch/3995236/mathematically_defining_functional_information_in_molecular_biology_kirk_durston/ Entire video: http://vimeo.com/1775160 for your second question, do you have any proof whatsoever, besides wishful speculation, that these machines arose from purely materialistic processes? “There are no detailed Darwinian accounts for the evolution of any fundamental biochemical or cellular system only a variety of wishful speculations. It is remarkable that Darwinism is accepted as a satisfactory explanation of such a vast subject.” James Shapiro – Molecular Biologistbornagain77_{March 16, 2010
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The operation of a grandfather clock can be explained by physics. You can describe the physical laws which allow the gravity mechanism to convert stored energy into motion, and how the ratios of the gears and the lengths of the pendulums translate into very good timekeeping. What natural laws can't explain is the presence of the clock itself with its precisely arranged parts, nor why it should keep time at all. The clock defies a natural explanation because no laws describe its assembly nor its purpose. We know that the clock does not form itself by any known physico-chemical process. That we can understand the physics of its operation does nothing to explain its presence. So it seems for biochemical mechanics. The physics and chemistry may explain the interactions, but they do not explain the system itself. Physics can explain the interaction between the parts of the grandfather clock, but the clock itself also needs explaining. The precise design and arrangement of parts cannot be explained by physics and chemistry. It's not the chemical interactions that design proponents have a problem with; it's the specific arrangement of protein parts that serve a purpose toward functional interaction. The parts and their composition defy natural explanation, not their chemical (or physical) interactions. This whole thread seems to be about semantics. I say that a computer doesn't actually perform facial recognition by itself. Someone else says that clearly it does, and that they can describe physically how it all takes place. What still needs explanation however is the computer itself, the algorithm, and the programming that made it happen. The mind performed the facial recognition, and used the computer as a tool to develop a set of rules for solving these types of problems autonomously. Much in the same way, a mind designed the clock and made use of physical laws to reproduce reliable behavior for the purpose of timekeeping. Natural laws are wholly inadequate as an explanation for either. Design proponents claim that the cell is in the same category as the clock (or the computer, with its software) -- that natural laws are inadequate to explain the intricate nano-machinery of biological organisms. This claim is refuted by showing by what natural laws govern the generation of such systems, absent intelligent design -- and not simply by demonstrating the physical laws by which they operate.Apollos_{March 16, 2010
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bornagain77 writes (61):
Pan, it is not a matter of the present existence of molecular machines and their obeying the laws of physics and chemistry in the present, it is a matter of the origination of these machines. i.e. Where did the functional information come from to build these machines in the first place?
Do you have a definition of "functional information" that would allow one to calculate it for, say, a strand of human DNA, a yeast cell, and a snowflake? Do you have any evidence that anything other than chemistry and physics was involved in the evolution of DNA repair mechanisms? Perhaps we'll get to the remainder of your post when these two issues are resolved.Pan Narrans_{March 16, 2010
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Pan, it is not a matter of the present existence of molecular machines and their obeying the laws of physics and chemistry in the present, it is a matter of the origination of these machines. i.e. Where did the functional information come from to build these machines in the first place? The Capabilities of Chaos and Complexity: David L. Abel - Null Hypothesis For Information Generation - 2009 To focus the scientific community’s attention on its own tendencies toward overzealous metaphysical imagination bordering on “wish-fulfillment,” we propose the following readily falsifiable null hypothesis, and invite rigorous experimental attempts to falsify it: "Physicodynamics cannot spontaneously traverse The Cybernetic Cut: physicodynamics alone cannot organize itself into formally functional systems requiring algorithmic optimization, computational halting, and circuit integration." A single exception of non trivial, unaided spontaneous optimization of formal function by truly natural process would falsify this null hypothesis. The Cell as a Collection of Protein Machines "We have always underestimated cells. Undoubtedly we still do today,,, Indeed, the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each which is composed of a set of large protein machines." Bruce Alberts: Former President, National Academy of Sciences; The Cell - A World Of Complexity Darwin Never Dreamed Of - Donald E. Johnson - video http://www.metacafe.com/watch/4139390/the_cell_a_world_of_complexity_darwin_never_dreamed_of_donald_e_johnson/ Cells Are Like Robust Computational Systems, - June 2009 Excerpt: "We now have reason to think of cells as robust computational devices, employing redundancy in the same way that enables large computing systems, such as Amazon, to keep operating despite the fact that servers routinely fail." http://www.sciencedaily.com/releases/2009/06/090616103205.htm Simulations reveal new information about the gateway to the cell nucleus Excerpt: “There are whole machines in living cells that are made of hundreds or thousands of proteins,” says Schulten, “and the nuclear pore is one of those systems. It’s actually one of the most magnificent systems in the cell.”,,,Hundreds to thousands of NPCs are embedded in the nuclear envelope of each cell,"... http://www.psc.edu/science/2006/schulten/ Articles and Videos on Molecular Motors http://docs.google.com/Doc?docid=0AYmaSrBPNEmGZGM4ejY3d3pfMzlkNjYydmRkZw&hl=en "There are no detailed Darwinian accounts for the evolution of any fundamental biochemical or cellular system only a variety of wishful speculations. It is remarkable that Darwinism is accepted as a satisfactory explanation of such a vast subject." James Shapiro - Molecular Biologist William Bialek - Professor Of Physics - Princeton University: Excerpt: "A central theme in my research is an appreciation for how well things “work” in biological systems. It is, after all, some notion of functional behavior that distinguishes life from inanimate matter, and it is a challenge to quantify this functionality in a language that parallels our characterization of other physical systems. Strikingly, when we do this (and there are not so many cases where it has been done!), the performance of biological systems often approaches some limits set by basic physical principles. While it is popular to view biological mechanisms as an historical record of evolutionary and developmental compromises, these observations on functional performance point toward a very different view of life as having selected a set of near optimal mechanisms for its most crucial tasks." Pan, since you mentioned quantum physics, are you aware that transcendent information is now shown to be independent of matter and energy? As well, are you aware transcendent information is shown to excercise dominion of matter and energy in quantum teleportation experiments? To top it all off Pan, materialists insist that consciousness has somehow arisen from a 3-dimensional material basis. Yet the double slit experiment, of quantum mechanics, shows that the "infinite quantum information waves" will not collapse to their "uncertain 3-D material particle states" until a conscious observer is present. So Pan, can you please explain how 3-D material reality gave rise to the consciousness that is required for its own existence? The only logical answer, for me, is that consciousness precedes the 3-D material realm and that consciousness resides within the infinite transcendent information realm.bornagain77_{March 16, 2010
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Hrun @59, The fact that knowledge of what to correct and how to correct it are necessarily required to actually carry out correction is damn near axiomatic. If one of those two conditions isn't met, then please offer a better alternative for how correction takes place, and how this proposal is substantiated with respect to reality. You seem to be completely bypassing one of the core tenets of science, that the person proposing a positive statement bears the burden of proof. Joseph's statement that correction requires prior knowledge of what and how to carry it out, as a principal, is confirmed on a daily basis in the real world. His burden of proof is fulfilled. Now it's your turn.
Nowhere are we talking about evolution. And nowhere is their factual support, positive or negative claim.
Your inability to recognize what constitutes proof for positive and negative claims (especially in light of a materialist predisposition) by no means objectively trivializes what you continuously refuse to accept. It moreso shows your own density as opposed to a true lack of proof as you continue to assert.PaulN_{March 16, 2010
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Way too many comments for me to reply to. Just real quick, I'll go with this one:
Hrun is taking advantage of the fact that it is very hard to prove a negative. It is hard to prove that error control mechanisms couldn’t possible ever evolve. So he says that Joseph’s assertions that they did not evolve are baseless.
In fact, Joseph didn't claim that and I did not ask for factual support for this assertion. Joseph made two specific claims, one positive and one negative (Blind molecules can’t identify anything, let alone correct mistakes. To identify and correct mistakes requires knowledge.) Nowhere are we talking about evolution. And nowhere is their factual support, positive or negative claim.hrun0815_{March 16, 2010
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I don't think the points made in this thread have been well communicated. It seems clear that everyone agrees proteins are involved in DNA repair. Joseph is really contending that a mind is required to create the molecules (proteins) to repair DNA. Opponents are contending that is not the case. The fact that chemistry ultimately does the work and no intelligent agent is directly present coordinating the repair process is irrelevant. That would be like finding a clock and stating that since no one was directly turning the hands the cause was not an intelligent agent. Joseph's assertion - based on experience, intuition and inference - is that any repair process requires foreknowledge of what is being repaired. Foreknowledge implies a designer. This is reasonable since this is always the case as we experience the world. We know from experience before we can fix something we must know what is wrong with it and in order to do that we must know what it is supposed to look like or work. A quick aside, up until fairly recently Fermats last theorom was unsolved. Prior to that would it have been reasonable to assert its validity? Quickly an example. Lets look at a DVD. It contains the encoded video stream but it also contains all error detection information and enough extra information so that even though it becomes scratched it can still be played. The software that decodes the stream of bytes needs to know the scheme being used in order to correct the video stream. Finally I agree Hrun and Pan. At least theoretically it would be possible for mutation to stumble upon a protein capable of repairing some kind of defect in the DNA even though this capability is likely never to be demonstrated. But I think the author of the original article says it best,
"It would be extremely unlikely for blind variations to stumble upon such protein designs. With evolution we must believe that such proteins just happened to arise and then were selected because they helped in the DNA repair system. If you believe that then I have a bridge to sell you."
andrewjg_{March 16, 2010
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Joseph writes (56):
Apparently not- but it does expose your agenda…
My only agenda is that I like to see debates like these proceed rationally. Failing to support one's assertions, and then failing to retract them, detracts from rational debate. If you have real support for your positions I would be very interested to hear it.Pan Narrans_{March 16, 2010
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Clive Hayden writes (55):
Pan,
If you or Joseph have any evidence that there is anything other than chemistry (and physics, of course) taking place as part of the DNA repair mechanisms, please present it. Otherwise Joseph’s claims remain unsupported assertions.
There is clearly information, just as when the body repairs itself, and a reductionist viewpoint such as chemistry and physics cannot be the whole show or the entire story. It would be like saying that a computer is clearly only chemistry and physics. This is all that really has to be shown, evidence using sense, it doesn’t have to be physical evidence, unless you’re steeped in materialism, which I am not, but presume you are.
Steeping? I'm positively bathing in the stuff! What I'm hearing, and please correct me if I'm misconstruing your position, is that biologists and biochemists have discovered a wide variety of repair mechanisms that use pretty well understood chemistry and physics to fix certain kinds of errors that occur when DNA replicates. Joseph comes along and, without demonstrating any knowledge of this work or any background in biology, chemistry, or physics, and simply states the equivalent of "That's just not possible." Surely you can understand that those of us with a background in one or more of those disciplines would require more than such a bare assertion to take the claim seriously. Now, as you note, reductionism isn't useful when discussing certain features of complex systems. It makes no more sense to talk about chemical reactions in terms of quantum mechanics (usually) than it does to talk about software in terms of electricity. However, noting that provides no evidence for the assertion that anything more than the laws of chemistry and physics are required to explain the observed DNA repair mechanisms. If you or Joseph want to move beyond unfounded assertions, you'll need to demonstrate clearly, with real physical evidence, that something other than what we've observed is required for those mechanisms to operate. A good way to tell when you're reaching the necessary levels of evidentiary support is when you can start making testable predictions about your claims.Pan Narrans_{March 16, 2010
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Pan Narrans, I have supported my claims. I cannot help it if you cannot understand what I post. Ya see Pan you don't have any evidence that living organisms are reducible to chemistry and physics. All you can do is use the example of DNA repair as evidence that DNA repair is carried out by blind molecules. Do you even realize how messed up that is? Apparently not- but it does expose your agenda...Joseph_{March 16, 2010
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Pan,
If you or Joseph have any evidence that there is anything other than chemistry (and physics, of course) taking place as part of the DNA repair mechanisms, please present it. Otherwise Joseph’s claims remain unsupported assertions.
There is clearly information, just as when the body repairs itself, and a reductionist viewpoint such as chemistry and physics cannot be the whole show or the entire story. It would be like saying that a computer is clearly only chemistry and physics. This is all that really has to be shown, evidence using sense, it doesn't have to be physical evidence, unless you're steeped in materialism, which I am not, but presume you are.Clive Hayden_{March 16, 2010
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Thanks for taking the time to surface the apparent question being begged Clive. And thanks Collins for identifying a tactic that was indeed taken advantage of beyond any rational means in order to justify assertions. I believe the logic is as follows: Proving that the molecular repair carried out by proteins in DNA correction wasn't a result of blind/random material chance+necessity follows the same difficulty as proving the stone formation within stonehenge wasn't a result of a nearby mountain exploding and rock shards falling into the specific pattern that we see today. While it's nearly impossible to actually prove the negative, it certainly is well within rational means to infer a more likely scenario for the positive, being that intelligence was the source of said phenomena according to real-world observations of what intelligence is able to create. The hypothetical alien vs. a force well known to commit murder according to direct and historical observation is a good analogy. The only thing I would change to make it more relevant with respect to the topic at hand is to change the hypothetical to something we know is much less capable of murdering someone and then framing them. For this I would change the story from an alien to a cockroach as the responsible party, which would further widen the rational gap between the conceivable possibilities.PaulN_{March 16, 2010
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Clive Hayden writes (52):
To argue as you do is to affirm your conclusion, that since there is DNA repair, there must be blind molecules, which is exactly what is in question.
If you or Joseph have any evidence that there is anything other than chemistry (and physics, of course) taking place as part of the DNA repair mechanisms, please present it. Otherwise Joseph's claims remain unsupported assertions.Pan Narrans_{March 16, 2010
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Pan Narrans,
Given the evidence for DNA repair mechanisms, it is not reasonable to take that position.
What Collin said was: "But it is reasonable to take the position that blind molecules cannot identify things. It is similar to the assumption that a machine cannot identify things without having been designed to do so. Otherwise you merely have pieces of metal and stone." And he's right. You took him out of context in truncating his statement in your quote. It is reasonable that blind molecules cannot identify things, unless, they have been programmed to do so. I think that was Collin's point. To argue as you do is to affirm your conclusion, that since there is DNA repair, there must be blind molecules, which is exactly what is in question.Clive Hayden_{March 16, 2010
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Pan Narrans, I have supported my claims. I can't help it if you are unable to follow along. And again you people who try to use the very thing that needs an explanation as an example for your position have serious issues. IOW you cannot point to DNA repair mechanisms as evidence for blind molecules doing something when it is that very DNA repair that requires an explanation. But I will tell you what- If you or anyone else ever demonstrates that a living organism can arsie from non-living matter via blind, undirected (chemical) processes I will retract everything I have ever said about blind molecules. Until you do that you don't have any evidence for your position. IOW your position is based solely of bald assertion after bald assertion.Joseph_{March 16, 2010
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Toronto:
An intelligent agency, in this case a patient in a hospital, scratches herself every day causing wounds on her arm. Every night, her body repairs the damage done by her intelligent actions during the day. No one has told the body what was injured or how to repair it, yet every night, her unintelligent biology repairs what her intelligent and concious actions have done.
Toronto- you cannot use what requires an explanation as the example for the explanation. That is just plain dumb.Joseph_{March 16, 2010
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Collin writes (47):
But it is reasonable to take the position that blind molecules cannot identify things.
Given the evidence for DNA repair mechanisms, it is not reasonable to take that position. We observe the biochemistry. A quick search turns up over a dozen papers in one issue of just one journal: http://www.sciencedirect.com/science/journal/15687864Pan Narrans_{March 16, 2010
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