Antibiotic Resistance Finding: Attempt two

Originally posted by Astyanax
There's no such story. Darwin didn't know anything about antibiotics, or drug resistance in bacteria. All that stuff happened long after his time.

That was poorly worded on my part. Of course Darwin didn't know about antibiotics; they're separated by about a century.

Sorry, mattison, you haven't satisfactorily demonstrated this - in fact, you haven't demonstrated this at all.

Ummm... yes I have, the Darwinian story re: antibiotic resistance is as I've described it. It's been subsequently modified because of discoveries like I've presented here. This is just further evidence that antibiotic resistance, in general, doesn't arise by natural selection acting on random mutation (the Darwinian story), it's always existed, and in fact propagates horizontally by complicated methods. None of that is coincident with Darwinian evolution.

All you have shown is that the modern synthesis as originally modelled back in the 1970s, at a time when biologists understood little more than that genes were somehow related to bits of DNA, did not account for all the facts of gene transfer.

It may show this too, but again, this isn't the point.

But that synthesis has long been modified to accommodate other mechanisms of gene transfer and exchange without doing any violence whatever to Darwin's theory.

Violence? No, not violence? It simply shows that Darwin's idea (natural selection acting on random mutation) is not only inadequate to account for the resistance, but is in fact wrong in this respect. The mutation is not random, it is generated in response to environmental stress, and as suggested in the articles posted occurs in a site-specific manner.

If you disagree, show us how I'm wrong.

Please see above statements regarding how antibiotic resistance isn't generated by NS acting on RM. It's NS acting on site-directed induced mutations.

My emphasis. You have not shown that it is directed, merely that a somewhat sophisticated autonomous response is in play. And this kind of mechanism is very much part of the modern evolutionary story - which is rather the point, isn't it?

Hmmm... would suggest you read the refs. The article details how use of antibiotics themselves triggers the synthesis of a specific bacterial enzyme that identifies and preferentially captures the resistance genes, and subsequently facilitates their expression.

The words 'identify and capture' imply that the proteins are identify, ie: are directed specifically to the resistance genes, which are then captured and expressed.

If identification, capture, and integration of specific genes isn't a process of directed then two questions: What is it? and What would directed mutation look like?

This is not directed mutation. It's an environmentally triggered response like any other. You're making it out to be more than it is.

No, you've either not read, or don't understand what the refs. are saying.

Of course the SOS system isn't present in sexually reproducing organisms! Myquoted statement assumes that. It isn't there because they don't need it: sex makes it unnecessary.

Sexual reproduction has nothing to do with DNA damage, SOS is simply replaced by other systems in eukaryotes, but sexual reproduction doesn't repair DNA damage, nor does it result in post-fertilization modifications and/or changes in the genome.

DNA doesn't need repair unless it is damaged, and all such damage must be triggered by factors in the environment, unless you are going to argue for uncaused events in a causal universe.

Completely untrue, and is contradicted by everything I've posted. These articles I've posted all talk about SOS induction in the absence of DNA damage.

That's the point. The DNA isn't damaged, it's being intentionally mutated.

Antibiotics, for the most part don't cause DNA damage. They cause cellular stress. The SOS system, the DNA repair system, in the ABSENCE of DNA damage induces mutation in specific regions of the genome.

Induction of mutation at a specific time, and at specific locations within the genome: explain to me how that is not directed mutation, and if inducing mutations in a temporal and sequence specific manner isn't directed mutation, then what is?

Cellular stress for a prokaryote is the same thing, precisely, as environmental stress; actually, is always is, even in eukaryotes

No it's not. The reason you can take antibiotics is because they cause stress in prokaryotic cells but not eukaryotic cells. The things that stress prokaryotic or eukaryotic cells are not the same, and given - as we've established - that the response systems are different in prokaryotes and eukaryotes, cellular stress isn't necessarily analogous in origin or response in prokaryotes vs. eukaroytes.

I doubt you are unaware of the Red Queen hypothesis, so I find it difficult to understand why you feel you can dismiss it out of hand.

Sure, but RQH says nothing about disease resistance.

VDJ recombination in eukaryotes, and the mechanisms I've cited here in this thread clearly demonstrate that an evolutionary arms race can be waged, and genetic diversity generated in the absence of sexual reproduction. The RQH says nothing about stopping disease, and is a bit of a non-sequitur here.

(From above source: in species where asexual reproduction is possible (as in many plants and invertebrates), coevolutionary interactions with parasites may select for sexual reproduction in hosts as a way to reduce the risk of infection in offspring.

See also the Wikipedia entry on the origins of sexual reproduction

Neither source mentions combatting disease as being a reason for sexual reproduction. They talk about genetic diversity and genomic redundancy.

No disagreement there. All the same, eukaryotes don't need an SOS-type response to swap genes; they have sex instead. Slower-acting but much more fun, as I'm sure you will agree.

Again, the SOS system isn't analogous to sex. If you want to compare SOS to something in eukaryotes, then perhaps homologous recombination, non-homologous end joining, or nucleotide excision repair; or if you want to compare eukaryotic sex to something in bacteria then let's talk about conjugation or integron swapping, but to say that SOS and sex are analogous in their benefit to the organism is simply false.

By swapping genetic material. By swapping genes.

No, by identifying, capturing, integrating, and reorganizing specific gene sequences at a specfic time. Please explain to me how that isn't directed mutation and what directed mutation would look like.

You folks seem quite knowledgable and I have enjoyed your debate.

I'm not sure if your aware of the use of sodium chlorite for the treatment of many diseases. This accomplished after it activates with a mild acid, such as citric acid, which then forms Chlorine Diode. Supposedly an oxicidizer.

I have tried this and find that it works well. I completely got over dengue fever within 6 hr of the onset. I have a friend that had AID/HIV and has fully recovered.

I was wondering what you thought of this as a healing agent and any thoughts you have about it method of operation.

I have read a few but they usually had an interest in the product. It would appear that it works against a host of diseases and the only down side that I have been able to find is an oxidative stress after prolonged use. Something having to do with red blood cells and there ability to take up oxygen which then seems to normalize rapidly after discontinuing its use.

I have read about chlorine dioxied being used as a water purifier, vegatable and meat purifier. I believe it was used in the anthrax attacks to sterilize the building. I have read of some studies and patients in canada that are using it interanlly and externally.

Its would seem that some do not want this info out as it is cheap and easy to use. Just wanting to get some more input from perhaps unbiased sources. Thanks. Sorry ab out the spelling errors. Its has never been my strong suit. Have not yet found a spell checker to use with ATS

[edit on 6-6-2009 by rken2]

[edit on 6-6-2009 by rken2]

Good, strong response, mattison.

Originally posted by mattison0922
Antibiotic resistance, in general, doesn't arise by natural selection acting on random mutation (the Darwinian story)

Agreed.

It's always existed...

No, only since it evolved.

...and in fact propagates horizontally by complicated methods.

Though no more complicated than immune responses in mammals (for example).

None of that is coincident with Darwinian evolution.

Sorry, but I must insist: nothing you have posted suggests this.

The mutation is not random, it is generated in response to environmental stress, and as suggested in the articles posted occurs in a site-specific manner.

You admit the environment as the ultimate trigger for the process that causes the mutation, then. We are in agreement on that, at least.

Antibiotic resistance isn't generated by NS acting on RM. It's NS acting on site-directed induced mutations.

Oh, I see. That's how you're looking at it. Well, as far as NS - natural selection - is concerned, a mutation is a mutation is a mutation: all grist to Nature's mill. Don't forget that Darwin begins his inquiry in Origin with a discussion of artificial selection. The question to ask is whether on not the gene capture process is an evolved character. Clearly it is. Again now, what was the question?

A specific bacterial enzyme that identifies and preferentially captures the resistance genes, and subsequently facilitates their expression.

Just as antibodies identify and preferentially capture specific pathogens. Again, I see nothing in this mechanism that cannot have developed through natural selection.

If identification, capture, and integration of specific genes isn't a process of directed [mutation] then two questions: What is it? and What would directed mutation look like?

1. A gene swapping mechanism that amounts to a kind of immune response.

Look at it like this. Bacteria under stress exchange genetic material. This is combined with a mechanism (admittedly a complex and rather wonderful mechanism) for making the best use of the captured bits. Thanks to the latter, some bacteria pick up the useful bits (such as genes that confer antibiotic resistance), acquire the benefit and pass it on when they divide; useless bits are picked up too, but the bacteria that get them are selectively disadvantaged and tend to be selected out of the population. Very Darwinian.

2. A fluorescent rat.

Sexual reproduction doesn't repair DNA damage.

Not in the individual, but it helps weed out deleterious mutations in the species. Müller's ratchet again.

Nor does it result in post-fertilization modifications and/or changes in the genome.

No, of course it doesn't. But see above. Again, sexual reproduction greatly reduces the need for all these ingenious shifts.

Astyanax: DNA doesn't need repair unless it is damaged, and all such damage must be triggered by factors in the environment...

Completely untrue, and is contradicted by everything I've posted. These articles I've posted all talk about SOS induction in the absence of DNA damage.

Hmm... you're right about DNA damage not being there. It will never be, because the bacterium in question would be killed by the antibiotic at the same time. But the mechanism is invoked under environmental stress, so whether or not there was DNA damage is hardly relevant. Clearly factors in the environment were - as ever - the trigger for the response.

The DNA isn't damaged, it's being intentionally mutated.

And whose was the intention?

Antibiotics, for the most part don't cause DNA damage. They cause cellular stress. The SOS system, the DNA repair system, in the ABSENCE of DNA damage induces mutation in specific regions of the genome.

Yes, see above.

Explain to me how that is not directed mutation, and if inducing mutations in a temporal and sequence specific manner isn't directed mutation, then what is?

Answered twice above, the second time by a question.

Astyanax: Cellular stress for a prokaryote is the same thing, precisely, as environmental stress; actually, is always is, even in eukaryotes

No it's not. The reason you can take antibiotics is because they cause stress in prokaryotic cells but not eukaryotic cells. The things that stress prokaryotic or eukaryotic cells are not the same...

They are not the same in terms of microbiological detail; but they are equivalent in their selective effect. All stresses on a prokaryote are by definition environmental.

RQH says nothing about disease resistance.

Parasite resistance. Same difference. Most diseases in the wild are caused by parasites.

VDJ recombination in eukaryotes, and the mechanisms I've cited here in this thread clearly demonstrate that an evolutionary arms race can be waged, and genetic diversity generated in the absence of sexual reproduction.

No quarrel with this bit; you are right, of course. And NS still operates.

To say that SOS and sex are analogous in their benefit to the organism is simply false.

A prokaryote is a species in the sense I mentioned above. Keep this in mind and the analogy becomes clear. The benefit, ultimately, is to the species. The benefit to the individual organism (in the case or prokaryotes) is simply incidental.

Please explain to me... what directed mutation would look like.

See above.

Is this just a "Which came first, the chicken or the egg?" argument?

mattison seems to be saying the process is not one of Darwinian-style natural selection.

Astyanax seems to be saying that while the process may not rely on natural selection, it did evolve from NS, so therefor it is NS.

...am distracted, not thinking clearly, but seems you both may be right - although imo mattison is more right.

Originally posted by mattison0922
The mutation is not random, it is generated in response to environmental stress, and as suggested in the articles posted occurs in a site-specific manner.

Or would it be better to say: "The mutations are random, the mechanism may not be"?

Researchers of the Molecular Microbiology Group at the UAB Department of Genetics and Microbiology have spent years studying the activation mechanisms of SOS response and now reveal that this response at the same time controls and increases the incorporation and mobility capacity of genes found within genetic elements known as integrons. One of the components of these genetic elements are genes which determine the resistance to a wide range of antibiotic and chemotherapeutic substances. Similar to the pieces of a jigsaw puzzle, integrons restructure themselves inside the DNA of bacteria by randomly adding, separating or rearranging their genes, thereby modifying the manner of expression and adapting to the needs of every moment, which are mainly defined by the stress conditions of the bacteria. Integrons can also transfer themselves from one bacteria cell to another and thus spread their antibiotic resistance genes.

[url=http://www.uab.es/servlet/Satellite?c=Page&cid=1096476786473&pagename=UAB%2FPage%2FTemplatePlanaDivsNoticiesdetall¬iciaid=1242971964865]linky[ /url]

So bacteria gets stressed, and one cellular response is to increase mutation rate (error-prone mechanism; SOS response - great name) and swapping of genes (integrons via SOS mechanisms) - and the integrons are 'shuffled' by enhanced random mutation. The integrons swapped may or may not contain the required genes? Considering the SOS response is involved in various stress responses, I doubt it seeks out particular genes in a directed manner, just does some swapping of genetic elements and then randomly shuffles.

If I take a pack of cards and deal them 10x faster than Astyanax, it would increase the chances of my dealing a royal flush in a particular timeframe. Like bacteria, once I have the royal flush, I'll be fitter than Astyanax and the natural selection mediated by the rules of poker will see me survive. Still essentially random though.

Darwin had no issue with the rate of evolution varying. Indeed, appears to be a mechanism (high fidelity during normal times, low fidelity during stress) that would increase fitness. Even Dawkins has no issue with changing rates of evolution over time (actually suggests it's a strawman to say otherwise).

New rearrangements are triggered by taking an antibiotics, and those bacteria that have 'correctly' rearranged their genes, creating a new resistance cassette, will be able to survive and pass on this resistance not only vertically, but also horizontally...

Aye, those that through the enhanced mutation rate produce resistance genes survive (RM and NS). They can then also pass them on laterally.

The not-random issue here is possibly the induction of an increase in mutation rate and genetic 'promiscuity', no? Mechanisms that help (directly or indirectly) generate diversity and variation. You can point to 'site-specific', but the changes are still random, lol.

And Mazel (2006) suggests that these mobile integrons probably evolved from superintegrons. Evolution of evolvability?

Mutation as a Stress Response and the Regulation of Evolvability

Authors: Rodrigo S. Galhardo abc; P. J. Hastings abc; Susan M. Rosenberg abc
Affiliations: a Department of Molecular and Human Genetics, Houston, Texas, USA
b Departments of Biochemistry and Molecular Biology, and Molecular Virology and Microbiology, Houston, Texas, USA
c The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA

Published in: Critical Reviews in Biochemistry and Molecular Biology, Volume 42, Issue 5 September 2007 , pages 399 - 435

Abstract
Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes.

Baer CF (2008) Does Mutation Rate Depend on Itself. PLoS Biol 6(2): e52. doi:10.1371/journal.pbio.0060052


Published: February 26, 2008

...

A correlation between fitness and mutation rate could have two (not mutually exclusive) underlying causes, one adaptive and one not adaptive. The “adaptive mutation” scenario has been influential in the world of microbial genetics, following the observation of Cairns and Foster [13] that Escherichia coli have higher mutation rates when starved (reviewed in [14]). The basic idea of adaptive mutation is that under normal conditions, low mutation rate is favored by selection because most mutations are deleterious. However, in a very poor environment, death is certain in the absence of a beneficial mutation that confers high fitness in that environment. Individuals with high mutation rates are more likely to “find” that beneficial mutation. Thus, natural selection will favor inducible mutation rates, which are low under normal conditions but greatly increased under stressful (i.e., low-fitness) conditions. Adaptive mutation remains controversial, but there is evidence from E. coli that the stress-induced mutation rate differs consistently with certain ecological circumstances [15].

Proc Natl Acad Sci U S A. 2002 June 25; 99(13): 8737–8741.
Published online 2002 June 11. doi: 10.1073/pnas.092269199. PMCID: PMC124368

Copyright © 2002, The National Academy of Sciences
Evolution
SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness
Bethany Yeiser, Evan D. Pepper, Myron F. Goodman, and Steven E. Finkel*


...The observation that pol V mutants show the greatest reduction in class 1 GASP competitions suggests that a subset of mutations, attributable especially to pol V, may provide the mutational “raw material” on which natural selection acts during the evolution of bacterial populations, in a manner superficially similar to the increased fitness accompanying the absence of MutSLH mismatch repair system (37–40). A key distinction to be drawn between the kinds of mutational events associated with the loss of MutSLH mismatch repair and those associated with the loss of SOS polymerases is that replication persists, under most conditions, whether or not the mismatch repair system is functioning, allowing the propagation of missense mutations.

This is extremely significant; the classic Darwinian story describes the organism as entirely a slave to the environment, unable to respond or adapt at the individuallevel

Jeez, I hope not. Psychology would be pretty boring otherwise.

It's cool that bacteria can respond like this, but they have to respond to stress somehow, lol. Other complex organisms have their own methods of overcoming stress - mindfullness works for me.

And, of course, integrons contain more than resistance genes (Mazel, 2006) and the SOS response is not restricted to just antibiotic-induced cellular stress. The best you can say is that bacteria may not be passive in cellular responses to stress (they can increase the potential for genetic variability via random mutation and lateral gene transfer). But the outcome is just enhanced run-of-the-mill evolution. You see, the genes have to have originally developed somehow, whether vertically or laterally derived.

And, matty, really, lol:

This is of course more evidence, another huge piece of evidence suggesting that The Theory of Evolution with respect Darwin's ideas is at least not as well understood as was once believed, and at most completely, utterly, and totally false.

So this evidence 'at most' takes down 150 years of research supporting Darwin's theory? Not likely, as noted by astyanax, just more details.

Anyway, back into my self-enforced exile. Hope academia's treating you well. I'll leave this to others to follow on - things to do and places to be.

[edit on 6-6-2009 by melatonin]

Originally posted by soficrow
Is this just a "Which came first, the chicken or the egg?" argument?

Not really. I made a slight error when I said the ultimate benefit is to the species. In the short term it is; in the long term, it benefits the genes themselves by preserving the species. But there is competition among genes (in a sense, all biological competition is between genes), and some genes gain a selective advantage by helping build useful stuff for other genes. The process that looks directed to mattison is driven by natural selection.

mattison seems to be saying the process is not one of Darwinian-style natural selection. Astyanax seems to be saying that... the process... did evolve from NS, so therefor it is NS.

This is correct, with the bit about 'not relying on natural selection' edited out as shown. All this genetic material floating about, some being preferentially captured and made part of the cellular community, others fading out... natural selection par exellence.

Originally posted by Astyanax
only since it evolved.

When I say "always" I mean ever since antibiotics were around. The appearance of antibiotics in an organism necessitates the appearance of resistance in that same organism; and it will rapidly lead to the appearance in other organisms

Though no more complicated than immune responses in mammals (for example).

Whether or not it's more-or-less complicated than anything is somewhat irrelevant. The point is that NS isn't necessarily - and in the case of antibiotic resistance - isn't acting on random mutation. That's the point. The complexity of other DNA recombination systems isn't relevant to the question at hand:

Question is NS and RM adequate to account for the appearance and spread of antibiotic resistance.
I say no because NS isn't acting on pre-existing RM, it's acting on newly established directed mutation.

Sorry, but I must insist: nothing you have posted suggests this.

No reason to apologize.

You admit the environment as the ultimate trigger for the process that causes the mutation, then. We are in agreement on that, at least.

I admit it? I've admitted since the first post. My point was, and still is this: Contrary to the story of Darwinian evolution, wherein nature selects more fit individuals based on pre-existing variation, the case of antibiotic resistance, at the very least, is adaptive; mutations are generated in response to some sort of environmental trigger.

So... I'm not admitting as much as I'm asserting it over and over. I'm glad people are finally catching on 20+ posts into this thread.

Oh, I see. That's how you're looking at it. Well, as far as NS - natural selection - is concerned, a mutation is a mutation is a mutation: all grist to Nature's mill. Don't forget that Darwin begins his inquiry in Origin with a discussion of artificial selection. The question to ask is whether on not the gene capture process is an evolved character. Clearly it is. Again now, what was the question?

There was no question. I generally don't come to ATS to have my scientific questions answered.

"That" is what I've been saying for more than 20 posts now....

The point is - and I'm glad you finally see it - is that the process of mutation is adaptive, and in my opinion, directed. The variation that NS acts upon isn't necessarily pre-existing, it can be generated in response to the environment.

Just as antibodies identify and preferentially capture specific pathogens. Again, I see nothing in this mechanism that cannot have developed through natural selection.

So were back to this... When did I say that something couldn't have developed via NS? I didn't I simply stated - for about the 25th time now - that mutation is adaptive, that is it occurs in response to the environment, and I further assert that it's directed. Adaptive mutation is hardly controversial, directed mutation is.

The point about antibodies is entirely moot. The point is that this bacterial enzyme IDENTIFIES GENES IN A SEQUENCE SPECIFIC MANNER, AND SUBSEQUENTLY INDUCES MUTATION IN THAT SPECIFIC GENE OR LOCI.

What do antigen-antibody interactions have to do with that?

If identification, capture, and integration of specific genes isn't a process of directed [mutation] then two questions: What is it? and What would directed mutation look like?

1. A gene swapping mechanism that amounts to a kind of immune response.

Your response conveniently ignores the fact that specific sequences are selected for this swapping, and these specific sequences are mutated. That's directed mutation.

It kind of doesn't matter anyway... you've shot yourself in the foot, and subverted yourself below.

Look at it like this. Bacteria under stress exchange genetic material. This is combined with a mechanism (admittedly a complex and rather wonderful mechanism) for making the best use of the captured bits. Thanks to the latter, some bacteria pick up the useful bits (such as genes that confer antibiotic resistance), acquire the benefit and pass it on when they divide; useless bits are picked up too,

Hmmm... what don't you understand about the word 'preferentially'? In this case, it refers to the fact that the bacteria select the useful 'bits' and ignore those they don't need, ie: it's directed.

but the bacteria that get them are selectively disadvantaged and tend to be selected out of the population. Very Darwinian.

Nice story, but it's not what the data say.

2. A fluorescent rat.

Interesting that you've selected this as an example of directed mutation? How do you think researchers make fluorescent rats? How do you think site-specific recombination is performed? It's performed using the enzymes, raw materials, and DNA sequences that the cell utilizes to recombine DNA.

The process of mutation in creating a fluorescent rat, is exactly the same as it is in cells. Fluorescent rats are only possible because the cell makes these enzymes etc.

The process that makes fluorescent rats - for the most part - is only unique at the level of selection. The researchers select out the cells that have the characteristics they want.

In other words the process of mutation if it's directed when you're making green rats, it's directed when the cell is using those same enzymes to attempt to generate antibiotic resistance. In the case of the former the selection is artificial, while in the latter, it's natural.

So... on the one hand the same process is directed when the selection is artificial, but on the other hand - that EXACT same process is NOT directed when the selection is natural....???

....okay....

Not in the individual, but it helps weed out deleterious mutations in the species. Müller's ratchet again.

Sexual reproduction doesn't help weed out deleterious mutations, it generates genetic diversity; NS weeds out deleterious mutations.

No, of course it doesn't. But see above. Again, sexual reproduction greatly reduces the need for all these ingenious shifts.

Really?!? Hmmmm..... that's interesting. If sexual reproduction reduces the need for "ingenious shifts" in genetic material, then WHY do the most complex systems for recombination and shuffling of DNA exist in those organisms that can reproduce sexually?

Hmm... you're right about DNA damage not being there. It will never be, because the bacterium in question would be killed by the antibiotic at the same time.

Nope. In this case, the organism HAS resistance genes. The DNA damage doesn't occur because it doesn't occur; the organism survives because of the ability to selectively and preferentially mutate or not mutate specific DNA sequences.

But the mechanism is invoked under environmental stress, so whether or not there was DNA damage is hardly relevant. Clearly factors in the environment were - as ever - the trigger for the response.

Sure it is. The point is that in the absence of DNA damage, bacterial cells will induce the expression of a DNA repair system to induce mutation in specific DNA sequences. The point is that the environment induces mutation - not via DNA damage, but as a response to the environment - and most importantly that the mutations occur in a sequence-specific, not genome wide manner.

The difference between directed and non-directed mutation is whether or not things occur in a sequence specific or genome wide manner.

And whose was the intention?

In my opinion bacteria are not referred to as 'who'.

Answered twice above, the second time by a question.

Yes, will it will be interesting to see how you deal with the rat question.

No quarrel with this bit; you are right, of course. And NS still operates.

My issue is not now, and never has been one with NS, always with the nature of mutation.

To say that SOS and sex are analogous in their benefit to the organism is simply false.

A prokaryote is a species in the sense I mentioned above. Keep this in mind and the analogy becomes clear. The benefit, ultimately, is to the species. The benefit to the individual organism (in the case or prokaryotes) is simply incidental.

No the analogy breaks down irresepective the scenario, because SOS and sexual reproduction don't function in an analogous manner, nor do they achieve analogous ends. When you compare SOS and sexual reproduction... it's apples to rocks...

Melly.... good to see you... I'll get to your post a bit later.

Originally posted by mattison0922
The point is that NS isn't necessarily - and in the case of antibiotic resistance - isn't acting on random mutation. That's the point.

Because the bacteria have evolved, through natural selection on random mutation, a mechanism to acquire useful genetic material? Genetic material that has evolved to be useful, again through natural selection by random mutation? And which will be acted on thereafter by natural selection, causing the bacteria to evolve further in the usual way? I say you have failed to make your case.

The selective character of the gene-transfer mechanism is not the point.

I have granted from the outset that the gene-capture mechanism you allude to is not random. Organisms of all kinds exhibit biochemical processes of a nonrandom character, all directed at survival and/or reproduction. All have evolved through natural selection - this one has, too. You say you admit this; what, then is your premise? That just because a process has been found within the ambit of evolved characters that involves gene swapping, Darwinian theory is somehow refuted? I think not.

This gene transfer, you say, is 'directed'. But when I ask 'who is the director?' you can only reply - in effect - 'the bacteria'. Are you asserting that bacteria have free will? That they possess intentionality? Surely not. Then you must mean that Someone Else is playing with genes in real time.

The ethical and metaphysical questions that raises are simultaneously daunting and ridiculous. He who sees the sparrow fall doubtless possesses the microscopic vision and manipulative resources necessary to go messing about with gene sequences in individual bacteria, but to invoke him as the Director of Antibiotic Resistance in this fashion would seem a little absurd. And no Director, mattison, equals no direction.

What don't you understand about the word 'preferentially'?

I don't understand why you're making such a big deal about a molecular selection process. How does this differ, for example, from preferential selection of amino acids in a ribosome? No doubt it differs in its mechanical details - but on a systems level, what is the difference?

Astyanax: The bacteria that get [the 'non-useful bits'] are selectively disadvantaged and tend to be selected out of the population.

Nice story, but it's not what the data say.

I disagree. From your source:

Plasmids contain genes for resistance and many other traits; they replicate independently of the host chromosome and can be distinguished by their origins of replication. Multiple plasmids can exist within a single bacterium, where their genes add to the total genetics of the organism. Transposons are mobile genetic elements that can exist on plasmids or integrate into other transposons or the host's chromosome. In general, these pieces of DNA contain terminal regions that participate in recombination and specify a protein(s) (e.g., transposase or recombinase) that facilitates incorporation into and from specific genomic regions.

What are we looking at here? A Darwinian competition among plasmids (or rather between genes) for uptake by bacteria. The contest is driven by random mutation in the usual way. One group of winners are the genes that code for antibiotic resistance. Where are the failures? Lost or on the way out.

Meanwhile, of course, the bacteria (who are also in Darwinian competition amongst themselves) also evolve incrementally more expert mechanisms for recognizing useful genes and incorporating them in preference to non-useful ones - raising the fitness bar in the competition between the plasmids, transposons, etc.

Interesting that you've selected this as an example of directed mutation? How do you think researchers make fluorescent rats?

Intentionally.

The process of mutation if it's directed when you're making green rats, it's directed when the cell is using those same enzymes to attempt to generate antibiotic resistance. In the case of the former the selection is artificial, while in the latter, it's natural.

And in that last sentences lies all the difference. The processes are not the same precisely because one is artificial and the other is natural. One is 'directed', by scientists in a lab; the other is an evolved, autonomous process. It is no more directed than the collapse of a train of standing dominoes is directed by a puff of wind that blows over the first domino in the train.

At the end of the day, mattison, your argument isn't scientific. It's legalistic: a quibble about whether Darwinian evolution has to be random by definition. You may as well say the existence of genetic engineers disproves Darwinism.

Originally posted by Astyanax
Because the bacteria have evolved, through natural selection on random mutation,

No. This is exactly what I'm refuting. I said that NS is the mechanism of selection, and I've pointed out - that in this instance the mutation is in fact not random.

a mechanism to acquire useful genetic material? Genetic material that has evolved to be useful, again through natural selection by random mutation?

I'm not talking about genetic material. I'm talking about the evolution of antibiotic resistance. The evolution of antibiotic resistance - clearly - as these papers indicate does not occur via NS acting on RM, it occurs via NS acting on directed Mutation.

And which will be acted on thereafter by natural selection, causing the bacteria to evolve further in the usual way?

The selection mechanism is not relevant here. No one is disputing the selection mechanism. The only thing ever disputed was the mechanism of mutation with respect to antibiotic resistance. Mutation, as these papers indicate, does not necessarily occur via random strochastic processes - the act of errors, chemical conversions and isomerisms, etc. It occurs via the expression of specific enzymes that have the role of mutating DNA... they're called error prone polymerases for a reason.

I say you have failed to make your case.

I say you fail to understand the argument, and can't keep the discussion on topic.

The selective character of the gene-transfer mechanism is not the point.

Hmmm... so you're going to dictate to me the point of my thread? Wow... I guess things have changed since I was last here at ATS

I have granted from the outset that the gene-capture mechanism you allude to is not random.

Then by definition, the same system that induces the mutations neither operates or behaves in a random manner. It's specific with respect to time of expression, loci where the mutation occur, and the conditions under which it occur... ie: it's directed.

Organisms of all kinds exhibit biochemical processes of a nonrandom character, all directed at survival and/or reproduction. All have evolved through natural selection - this one has, too.

Things have no choice but to evolve via NS, there's no other selection mechanism present in nature.

I'm sorry this is so difficult, but I've never disputed NS, don't dispute NS, and honestly think it's quite foolish to dispute NS.

What I do dispute is whether or not antibiotic resistance evolves via NS acting on RM, I say no. I say antibiotic resistance has evolved via NS acting on DM. I've presented scholarly research - which you, in the very post I'm responding to - have admitted doesn't operate in a random manner. But for some strange reason, you can't keep the discussion on the topic of DM, and for some reason keep refuting this strawman of NS, and saying that somehow the selection mechanism is critical.

The selection mechanism is downstream from the mutation mechanism and is not in fact critical or even relevant to my argument.

Indeed as the fluorescent rat example - which you don't understand - demonstrates, the selection mechanism can be either natural (antibiotic resistance) or artificial (fluorescent rats).

You say you admit this; what, then is your premise? That just because a process has been found within the ambit of evolved characters that involves gene swapping, Darwinian theory is somehow refuted? I think not.

Nope. I'm sorry this is so difficult for you to read through. Take your "skeptical" glasses off for a moment, and read with a bit of openness and clarity. What I said is that the Darwinian mechanism of NS acting on RM in the case of antibiotic resistance is not coincident with modern evidence. In fact, what is coincident with modern evidence is that NS is acting on DM.

This gene transfer, you say, is 'directed'. But when I ask 'who is the director?' you can only reply - in effect - 'the bacteria'. Are you asserting that bacteria have free will? That they possess intentionality? Surely not. Then you must mean that Someone Else is playing with genes in real time.

Ahhh yes. And here we have a large degree of clarity. Your perception of the world is so focused on refuting metaphysical arguments that you read things that are not present.

You see what we have here is someone who believes the term 'directed' implies God, or Intelligent Design, or [c]reation with either a capital or lowercase c. Because I have said directed, what I ultimately mean is that God is the director, God is making the mutations, etc.

I've said nothing of the sort, and you yourself don't even believe that only God, or an intelligence for that matter, can 'direct' something. Just look at this next paragraph.

The ethical and metaphysical questions that raises are simultaneously daunting and ridiculous. He who sees the sparrow fall doubtless possesses the microscopic vision and manipulative resources necessary to go messing about with gene sequences in individual bacteria, but to invoke him as the Director of Antibiotic Resistance in this fashion would seem a little absurd. And no Director, mattison, equals no direction.

There are neither ethical nor metaphysical questions or implications in anything I've said. As I mentioned above, you yourself don't believe that only an intelligence is capable of directing something. I'll point that out in just a bit.

The irony here is that it's in fact you who can't see beyond your own metaphysical assumptions to even read something with which you think you may disagree with a semblance of clarity. You have made the assumption the because said "directed" that I'm somehow invoking God. I've made no such claim, and have no such claim in mind.

I've been very specific in what I've said the Darwinian mechanism NS acting on RM doesn't comport wth reality in the case of antibiotic resistance.

I don't understand why you're making such a big deal about a molecular selection process.

Yes, it's quite clear you don't recognize the significance of this.

How does this differ, for example, from preferential selection of amino acids in a ribosome? No doubt it differs in its mechanical details - but on a systems level, what is the difference?

Who said it's different? I didn't. And this is what you've all been waiting for. This quote above clearly demonstrates that 'directed' does not necessarily imply intelligence. The process you mention, translation is clearly not random, ie: its directed.

The ethical and moral questions you've just posed are daunting and ridiculous...

Sorry, I couldn't resist the opportunity.

This doesn't mean there's some Great Translator in the Sky. The processes is directed. It's directed by mRNA; mRNA directs the synthesis of polypeptides.

What are we looking at here? A Darwinian competition among plasmids

Nope. There's no competition among plasmids. If you'd read the source, you'd read that the plasmids, once they are effective are maintained... that is they are no longer selectively mutated, they are simply passed on. So there aren't different plasmid strains per se, just populations of bacteria that contain the same plasmid. So... no.

(or rather between genes) for uptake by bacteria. The contest is driven by random mutation in the usual way.

Nope. The contest is driven by directed mutation. Since, apparently, directed mutation - either via direct plasmid uptake, reshuffling of existing integrons, or the induction of point mutations - is the way this occurs, I suppose it's accurate to call this "normal".

One group of winners are the genes that code for antibiotic resistance. Where are the failures? Lost or on the way out.

Those who don't acquire the resistance, which is acquired via a directed process.

Meanwhile, of course, the bacteria (who are also in Darwinian competition amongst themselves)

As far as I'm concerned the competition isn't Darwinian if the variation isn't random. If the variation is generated in response to some environmental cue, then that isn't Darwinian... clearly.

also evolve incrementally more expert mechanisms for recognizing useful genes and incorporating them in preference to non-useful ones - raising the fitness bar in the competition between the plasmids, transposons, etc.

Yes, but the process of mutation of generating new genetic material is frequently, directed.

Intentionally.

And in that last sentences lies all the difference. The processes are not the same precisely because one is artificial and the other is natural.

One is 'directed', by scientists in a lab; the other is an evolved, autonomous process.

No. Both reactions utilize the same processes. One is occurring in the environment the other is occurring in a test tube, but the components, raw materials, and - most importantly - the biological processes are the same. The process is an evolved autonomous process in both cases. The only difference occurs at the level of selection... downstream of the mutation. The selection is quite irrelevant.

It is no more directed than the collapse of a train of standing dominoes is directed by a puff of wind that blows over the first domino in the train.

Interesting analogy. The train of dominoes is directed, the puff, the environmental cue is not, however, the way in which the dominoes fall is absolutely directed.

a quibble about whether Darwinian evolution has to be random by definition

It does have to be random; its part of the definition.

You may as well say the existence of genetic engineers disproves Darwinism.

That's a horrible analogy. nonsensical