Posted on 02/14/2002 3:30:12 PM PST by jennyp
Why?
Back to proofreading topic; here from a PNAS search:
GeneticsSo there is evidence that without a proofreading function, error rates for bio-chemical self-replicators are too high to provide survivability, and therefore evolvability.Mutants in the Exo I motif of Escherichia coli dnaQ:
Defective proofreading and inviability due to error catastrophe
(fidelity of DNA replication / dnaQ and dnaE genes / mutD5 mutator / dnaE antimutators / saturation of mismatch repair)
Iwona J. Fijalkowska* and Roel M. Schaaper
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
Communicated by Maurice S. Fox, Massachusetts Institute of Technology, Cambridge, MA, December 11, 1995 (received for review October 27, 1995)
The Escherichia coli dnaQ gene encodes the proofreading 3' exonuclease ( subunit) of DNA polymerase III holoenzyme and is a critical determinant of chromosomal replication fidelity. We constructed by site-specific mutagenesis a mutant, dnaQ926, by changing two conserved amino acid residues (Asp-12Ala and Glu-14Ala) in the Exo I motif, which, by analogy to other proofreading exonucleases, is essential for the catalytic activity. When residing on a plasmid, dnaQ926 confers a strong, dominant mutator phenotype, suggesting that the protein, although deficient in exonuclease activity, still binds to the polymerase subunit ( subunit or dnaE gene product). When dnaQ926 was transferred to the chromosome, replacing the wild-type gene, the cells became inviable. However, viable dnaQ926 strains could be obtained if they contained one of the dnaE alleles previously characterized in our laboratory as antimutator alleles or if it carried a multicopy plasmid containing the E. coli mutL+ gene. These results suggest that loss of proofreading exonuclease activity in dnaQ926 is lethal due to excessive error rates (error catastrophe). Error catastrophe results from both the loss of proofreading and the subsequent saturation of DNA mismatch repair. The probability of lethality by excessive mutation is supported by calculations estimating the number of inactivating mutations in essential genes per chromosome replication.
Do the mutations discussed exclude self-induced mutations?
Because questions like "Why?" and "How?" are intrinsic to the observation that nitrogenases are oxygen sensitive. Julie Thomas, after playing twister for a while, arrives "by design" at the very question that is the starting point for the naturalist.
So there is evidence that without a proofreading function, error rates for bio-chemical self-replicators are too high to provide survivability, and therefore evolvability.
Too many mutations lead to error catastrophy and too few mutations don't lead to change. This is well known. And it's also well known that this places similar constraints on early replicators. The only conclusion I can draw from the abstract is that the E. coli dnaQ gene must not have been the first replicator!
LOL. Jumping the gun, just a little, aren't you?
This is not a satisfying response to me. The Thomas paper is 30 pages or so, half of which is dedicated to the discussion of nitrogenase; it’s role for the organism, it’s role in terraformation (whether foreseen or not), evolutionary explanations for its existence, problems with those explanations, nitrogenase from a design perspective, and problems with that perspective.
Here’s more from Thomas on nitrogenase:
The more I think about nitrogenase, the more it makes sense in light of design and terraforming. It is often said that one way to show design is to find a biological feature that is useless to the organism that possesses it, but benefits other organisms. This would be unexplainable from the perspective of natural selection. But it would also be a terrible design strategy, as any feature that is useless to an organism is no different from a pseudogene and thus would quickly decay. If you want to design a feature that is useful to other organisms, then the feature must also be useful to the organism that possesses it so that natural selection can be used to maintain and propagate it. Nitrogenase may not be useless, but it is so costly that many bacteria have gotten rid of it. For not only does it cost so much ATP that growth suffers significantly, but cells must also have strategies to protect the nitrogenase from oxygen. Thus, in terms of individual benefit, nitrogenase activity is not overly impressive. But in terms of benefit for the biosphere, it is essential. If, for example, nitrogenase was lost among all bacteria 2 billion years ago, it is quite doubtful life would exist today (or it would exist only minimally as few single- celled organisms). Nitrogenase is at the heart of the ecological nitrogen cycle. Thus, here is an example where a molecular machine seems far more important to the biosphere than any particular organism possessing the machine (organisms can lose it, but the biosphere cannot).Of course, this costly machine also poses a design problem to terraforming. This problem can be formulated as follows:
How do you design bacteria-like cells, for the purpose of terraforming, so that your costly nitrogenase is not completely lost by all bacteria over time?
From my perspective, do I give more credence to the thoughtful and thorough detailed analysis (that admittedly is a bit over my head) from Thomas, or a one sentence dismissal without explanation from someone whom I respect?
Compare Thomas’ hypothesis, which you call foolishness, to this recent press release:
Hydrothermal vents, for example -- areas on the ocean floor that expel seawater superheated deep in the Earth's crust -- and the exotic creatures that live there have received increased attention. Now scientists are scrutinizing another location for clues in unraveling some of life's riddles -- deep in the ground, underneath the planet's surface. "We've pretty much left Darwin's warm little pond in the dust," said David Stahl, a University of Washington professor of civil and environmental engineering whose work focuses on ecology and evolution. "The subsurface is being increasingly viewed as an important and largely unexplored part of the biosphere. Depending on how you calculate it, its biomass may exceed the biomass on the surface of the planet."In years past, scientific speculation about how life began on Earth envisioned primordial soups and slimy goo as the incubators in which the first tiny microorganisms developed, billions of years ago. More recently, microbiologists have examined places formerly seen as too harsh and inhospitable to foster biology, seeking answers about how life developed and adapts.
Is this speculation just "foolishness" in your opinion? Before you answer, let me give you my take.
This is a prime example of methodological naturalism putting the cart before the horse. Did life start near hydrothermal vents? Did life start deep in the earth's crust? Did life start in the primordial soup? Did life start high in the atmosphere? I’ve read all of these speculations and more.
How about this question: Is it possible for non-cellular protolife to even exist or perpetuate at all? I mean come on! Shouldn't we try to answer this question before taking wild guesses about some origin location? No one has found any protolife. No one has bioengineered any protolife. There's no evidence for chemical evolution. Replicators without proofreading yield to error catastrophe. Simplest cellular life contains dozens of IC molecular machines, which we know cannot evolve in direct Darwinian fashion. Is it just me? If I asked "Does Big Foot prefer the beach or the mountains?" and then had a huge debate with my fellow Big Foot enthusiasts, wouldn't some astute observer break in with, "Do we know if Big Foot really exists?"
The methodological naturalistic assumption requires the conclusion that life came about by abiogenesis. If we assume Big Foot, I guess it wouldn't be so silly to discuss his preference for the mountains over the beach!
The only conclusion I can draw from the abstract is that the E. coli dnaQ gene must not have been the first replicator!
There’s a problem here. In order to avoid error catastrophe, we infer from this that the first replicator must have been a more reliable replicator than proofreadingless E. coli. But if this is so, why evolve proofreading at all? Why not just depend upon Natural Selection to evolve the ideal rate of mutation?
The alternate view is that replicators within the bio-chemical platform are just inherently error-prone . . . too error prone to sustain themselves without proofreading. This view is also supported by my Goodwin quote. (I recall reading somewhere that proofreading improves fidelity by a factor of 50,000! Don’t quote me. This is off the top of my head.)
It's because you don't get it. You're in manic mode and can't finish one thought before flitting to the next barage of quotes.
In the section I quoted to you, Thomas invokes 'design' as an aid to arrive at a question which is obvious without invoking design. Can you comment on that?How is the design perspective helping her? I made no comment on her "terraforming hypothesis"--I haven't read anything beyond what you posted. It sounds gaia-ish.
Because things evolve.
Why not just depend upon Natural Selection to evolve the ideal rate of mutation?
There's your answer.
Well that is my interpretation of the statement made by Shapiro, "removes the process of genome restructuring from the stochastic realm of physical-chemical insults to DNA and replication accidents". And I do qualify my statement in post 179 by saying "if this analysis is correct".
I leave it to the lurkers to judge the coherence of my thoughts. If you don't want to talk about this, no one is forcing you. I'll see you later.
-- jazz
How do you select for something that is supposed to be random?
Ah, the age of enlightenment – ‘I think therefore I am’ – how could any bolder statement be made.
But the question, ‘why do we think?’, has yet to be answered.
So we turn to science, but it can only give the absolutes as provided by nature, the laws that describe the Universe and the physical. How can science describe the intangibles, i.e. thoughts?
Evolutions’ Big Bang – Thoughts just appeared – just like the Universe. Just accept it now and science will prove this later. This surly could not be based on faith.
But even if this were to be proven true – our intelligence came from nothing? How could this be trusted coming from our own minds?
For science to prove this, nature itself would need intelligence, and we would then need to prove that nature happened by chance.
Or maybe we could just come up with some politically correct words to better describe ID>
You're not incoherent. I'm frustrated that you don't finish one issue before moving on to the next. I am trying to move you back to the discussion of Julie Thomas and her use of 'design' in forming questions. Do you have any comments on that?
Are you are arguing that there is no intelligence behind your own intelligence. LOL!
Of course. But, Shapiro is talking about specific kinds of mutations, that of directed insertions of transposable elements. Genome restructuring by elements intrinsic to the organism is, then, an explanation for punctuation or major innovation.
That is not how I interpret stochastic realm of physical-chemical insults to DNA.
Did you read the paper?
No. I just made up those quotes.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.