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Author Topic:   Wright et al. on the Process of Mutation
Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 4 of 296 (627336)
08-02-2011 5:01 AM
Reply to: Message 3 by Taq
08-01-2011 11:14 PM


Re: Background on strains, genes, and biochemistry
That seems like a very concise introduction but there are a few points.

The strains are called CP78 and CP79 throughout the paper.

I would also suggest that the 'modified' Lac promoter, tac, is more accurately described as a fusion of two different promoters, the trp and lac uv5 promoters. I'd usually consider a modified promoter to be one that has been subjected to targeted mutations to alter its sequence rather than a chimera/fusion as in this case.

TTFN,

WK


This message is a reply to:
 Message 3 by Taq, posted 08-01-2011 11:14 PM Taq has responded

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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 12 of 296 (627641)
08-03-2011 6:31 AM
Reply to: Message 11 by Dr Jack
08-03-2011 4:56 AM


Re: Their claim is not well supported.
they haven't worked out the prevalence of the mutation in the basal population.

Without doing a population wide sequencing screen there would be no way to detect such revertants in an unstarved population. The selective conditions that would reveal the mutation through a standard screen would themselves trigger the starvation response. What the authors do is to use starvation for another amino acid, threonine or arginine, as the control condition for culturing prior to plating.

It is definitely worth noting that in fact these levels are essentially the same as those for cultures raised in leu starved conditions as those raised in arg starved conditions. Unfortunately revertants arising before or after plating can't be ditinguished, again short of wide scale genetic screening, so there is no way to tell when the reversions occurred.

I think we might be kind of preempting Taq's progression through the paper a bit.

TTFN,

WK


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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 17 of 296 (627900)
08-05-2011 4:41 AM
Reply to: Message 16 by Taq
08-04-2011 10:03 PM


Fig.3
Technically an RNase protection assay (RPA) is not a blot since there is no transfer of the sample material, instead the gel the sample is run out on is dried down straight onto filter paper to make it more stable. I spent practically my whole PhD running those damn things!

I have to say that looking at that RPA it doesn't really seem consistent with the data from figure 2 or Table 1. In Fig. 3 it looks like there is a definite induction of leuB in the starved CP79 relA- sample.

The induction is certainly massively higher in the relA+ strain, but it just seems strange that the only actual raw data they show doesn't really look consistent with the other derived figures.

It is a bit strange that they present exactly the same sort of data, RPAs, in two different ways in this paper. Although all of the data figures are from RPAs only Fig. 3 shows the actual bands on gel. If I were cynical I'd say that it suggests that the gels were pretty messy and possibly hard to interpret, though going by the derived graphs the results should have been pretty clear.

TTFN,

WK


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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 54 of 296 (631629)
09-02-2011 4:43 AM
Reply to: Message 53 by Percy
09-01-2011 9:47 PM


I'm not so sure
Hi Percy,

I'm not sure your interpretation is right.

I think that what he means by "these alles production are more than those w/o the mutation" is in fact that these mutations occur de novo at a higher frequency in populations to which they would be beneficial.

This seems the logical interpretation since that is what Shadow71 has been arguing for the entire rest of the thread.

Admittedly the sentence is so badly written it is hard to tell exactly what Shadow is wrong about, apart from the Darwin bit of course which you nailed.

TTFN,

WK


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 Message 53 by Percy, posted 09-01-2011 9:47 PM Percy has responded

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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 62 of 296 (632779)
09-10-2011 4:32 AM
Reply to: Message 61 by zi ko
09-10-2011 1:32 AM


Re: beneficial mutations
Also there is the possibility that organism in succeeded generations will produce more of the "apropriate" mutations if it sees it usefull.

How on Earth would this latest ad hoc nonsense work? The organisms where the mutation is beneficial already have it. In what way would the other wild-type organisms 'see' that a particular mutation was beneficial in successive generations. You are going far beyond directed mutation mechanisms in a cell here to some sort of population wide communication phenomenon directing the de novo replication of specific mutations. In other words from a tenuous hypothesis to one that is a complete fabrication without a scintilla of evidence.

Of course there already exists a well known mechanism by which beneficial mutations will tend to proliferate in subsequent generations, it is called natural selection.

TTFN,

WK

Edited by Wounded King, : No reason given.


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 Message 61 by zi ko, posted 09-10-2011 1:32 AM zi ko has responded

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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 70 of 296 (633269)
09-13-2011 11:57 AM
Reply to: Message 67 by zi ko
09-13-2011 10:09 AM


Re: beneficial mutations
Again you seem loathe to put forward anything that might constitute evidence of any sort. If there were evidence for such population level interactions I'm not sure why we would not have been able to detect it. The mechanisms by which discrete unicellular Dictyostelium amoebae can interact to form motile colonial aggregates in response to stress is well understood, why is a similar mechanism for directed mutation in the heavily studied field of bacterial population genetics so febrile and cryptic?

But you don't mention at all how many were the none beneficial mmutations in that particular event.

Because the Wright paper does not provide any way to get that information. The only mutation rate figures they provide are for the Leu reversion.

TTFN,

WK


This message is a reply to:
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Replies to this message:
 Message 76 by zi ko, posted 09-16-2011 4:23 PM Wounded King has responded

    
Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 77 of 296 (633831)
09-16-2011 5:15 PM
Reply to: Message 76 by zi ko
09-16-2011 4:23 PM


Re: beneficial mutations
Those are 2 distinct things and neither of them leads to coordinated directed mutation between members of a population. Certainly there is evidence that some organisms, at least bacterial ones, have mechanisms which can increase their mutation rates in response to stress, no problem. I don't think you would find anyone here who quibbles with that. But that doesn't show directionality to the mutations that are produced.

Wright argues reasonably that there is something that could be considered directionality favouring more actively transcribed genomic regions, and that relevant genes may be more likely to be transcribed as part of a stress response. So far that is as far as the evidence goes, and it goes nowhere near the enormous leaps beyond the evidence you are taking. Indeed, neither of the things referred to in the Shapiro quote are about population level effects.

TTFN,

WK

Edited by Wounded King, : No reason given.


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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 79 of 296 (634102)
09-19-2011 8:51 AM
Reply to: Message 78 by shadow71
09-18-2011 7:08 PM


Re: beneficial mutations
My question is does directionality favoring more actively transcribed genomic regions where more revelant genes may be more likely transcribed concur with the Neo-Darwinism of the late 1960s?

I'm not sure why you want to specifically argue against evolutionary theory as it stood more than 50 years ago, but then Wright seems to want to argue against evolutionary theory from the end of the 19th century (She identifies the neo-Darwinism that her results call into question as that of Weismann, citing a reference from 1893), so at least your target is a bit more relevant. Ernst Mayr would disagree with you and Wright that what you are discussing is neo-Darwinism as he drew a clear distinction between Weismann's theory and the modern synthesis as formulated in the 30s and 40s.

I really don't see why you picked the late 60s, that is well after the formulation of the modern synthesis. Is there any reason why you don't want to discuss actual modern evolutionary theory?

If you could specify a particular theorist or group it might help, it isn't as if evolutionary theory in the late 60's was a monolithic block with everyone marching in lock step any more than it is today. There were a number of heterodox theories at the time many of which have since fallen out of view as they were not supported by the evidence but some of which, as with Kimura's neutral theory, have become widely accepted.

To return to your question; on the whole I'd probably say the answer is maybe, it certainly doesn't contradict anything particularly. It barely even constitutes a contradiction of Weismann's neo-Darwinism, since that was principally concerned with the distinction between germ line and somatic lineages, a distinction that doesn't exist in the model in Wright's study.

TTFN,

WK

Edited by Wounded King, : No reason given.

Edited by Wounded King, : No reason given.


This message is a reply to:
 Message 78 by shadow71, posted 09-18-2011 7:08 PM shadow71 has responded

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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 86 of 296 (634374)
09-21-2011 4:37 AM


Balderdash
Anyone interested in Boulder-dash's persistent failure to comprehend the different ways the term 'Modern synthesis' is used can read the last time he and I discussed this issue starting at Message 284 in the Criticizing neo-Darwinism thread.

I'm not going to have the same discussion again here and drag this thread even further off topic, if BD wants to continue this line of argument I suggest he return to the thread where he was already making it.

Remember when this thread was going to be a focused discussion of a specific scientific paper and what it showed? Great days.

TTFN,

WK

Edited by Wounded King, : No reason given.


    
Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 90 of 296 (634486)
09-22-2011 4:18 AM
Reply to: Message 89 by zi ko
09-21-2011 9:51 PM


Life's persistence
Mutations are random, but only to fitness, not to life perseverance.

This is essentially a tautology, although life is hard to define precisely many proposed definitions involve the capacity for change and adaptation including mutation and reproduction (Koshland, 2002; Clelland and Chyba, 2002; McKay, 2004).

All you seem to be saying here is that for life to persevere there need to be things continuing to exist which still show the characteristic properties of life. Which is kind of obvious.

TTFN,

WK

Edited by Wounded King, : No reason given.

Edited by Wounded King, : No reason given.

Edited by Wounded King, : No reason given.


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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 113 of 296 (635104)
09-26-2011 6:53 PM
Reply to: Message 109 by Taq
09-26-2011 12:03 PM


Nitpicks and an interesting reference
Taq writes:

That is false. Neo-Darwinism did not exist in 1893. It didn't come to fruition until the 1940's, and it has matured since then. Environmental influences on the random mutation rate is a part of the Modern Synthesis (aka neo-Darwinism).

This isn't actually correct Taq.

The problem is that terms describing various developments in evolutionary theory over the years have become conflated together, specifically 'Neo-Darwinism' and 'The Modern Synthesis'.

The term neo-darwinism is from a description of Weismann's work by George Romanes another biologist contemporary to Darwin and Weismann. It is a distinction based on the discrete germ line inheritance model of Weismann compared to Darwin's blending inheritance model.

While I'm in my nit-picking mode I'd also direct some at Percy who substantially misrepresented Weismann's position which was principally concerned with the genetic separation between the somatic and germ line cells in metazoa.

Rather than the vague term 'environment' what Weismann studied was whether use and disuse, of specific traits, or physical changes affected inheritance. The sort of Lamarckism Percy seems to be describing in terms of environmental influence is a much more modern conception. Specifically Weismann used mice to study whether docking tails over successive generations would give rise to tailless offspring.

So that is the original concept of Neo-Darwinism and it is distinct form the population genetics based Modern Synthesis of the 30s and 40s.

Just one more thing, not strictly related, while I was searching around for a while ago looking at stuff on different definitions of 'random mutation' I found an article that seems quite pertinent.

Rather unusually for me it isn't from the scientific literature but instead from 'Philosophy and Theory in Biology', an online open-access philosophy journal. The paper is Evolutionary Chance Mutation: A Defense Of the Modern Synthesis’ Consensus View (Merlin, 2010), the abstract reads ...

Merlin writes:

One central tenet of the Modern Evolutionary Synthesis (1930s-1950s), and the consensus view among biologists until now, is that all genetic mutations occur by “chance” or at “random” with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the “chance” vs “directed” character of mutations (1980s-2000s). In fact, some argue that mutations due to a particular kind of mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis’ consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb’s analysis of genetic mutations (2005) and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of “evolutionary chance,” which I claim is the Modern Synthesis’ consensus view and a reformulation of Darwin’s most influential idea of “chance” variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis’ paradigm.

Definitely worth a look.

More specifically relevant to this topic is Merlin's critique of the 'directed' interpretation of Wrights work which strongly echoes what Taq has been saying throughout this thread ...

Merlin (2010) writes:

The beneficial mutation at the level of the leuB gene fulfills the first but not the second condition to be a “directed” mutation and is therefore an “evolutionary chance” mutation according to the Modern Synthesis’ consensus view (see above, Section 5). The mutation from LeuB- to LeuB+ is more probable in an environment where bacteria are in leucine starvation than in an environment where the mutation is neutral or deleterious (e.g., in a milieu rich in leucine). This is due to the increase of the mutation rate targeted at the leu operon in response to leucine deprivation. However, the probability of this beneficial reverse mutation occurring is not higher than for other neutral or deleterious mutations in the same leucine deprived environment. In fact, Wright and her colleagues observed that this increased mutation rate is not only targeted at the leuB gene, where a mutation could allow bacteria to survive and reproduce, but at all the genes of the leu operon as well. Therefore, the reverse beneficial mutations at the level of the leuB gene may seem to be “directed” simply because it is easier to detect than mutations occurring in these other genes, which may either grow slower or be negatively selected. Thus, since bacteria carrying the reverse beneficial mutation from LeuB- to LeuB+ are positively selected and contribute to the next generation, they can be easier to detect and quantify than bacteria with other mutations.

TTFN,

WK

Edited by Wounded King, : No reason given.

Edited by Wounded King, : No reason given.


This message is a reply to:
 Message 109 by Taq, posted 09-26-2011 12:03 PM Taq has responded

Replies to this message:
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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 120 of 296 (635137)
09-27-2011 5:42 AM
Reply to: Message 117 by Percy
09-26-2011 8:25 PM


Re: Nitpicks and an interesting reference
Well to some extent you have to look outside of this specific paper by Wright, the other Wright paper Merlin cites is entitled "A Biochemical Mechanism for Nonrandom Mutations and Evolution". It is also worth bearing in mind that it is Wright who claims that her research is overturning 'current neo-Darwinian dogma'.

If one should equate non-random with directed is another question and one that the Merlin paper deals with at length. If you feel that Wright's 'non-random' mutational claims are distinct from claims of 'directed' mutation then fair enough. Merlin is more focused on the way the work has been presented by Jablonka and Lamb in their book "Evolution in 4 dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life."

Fro the most part Merlin merely describes the actual specifics of Wright's work on the LeuB- strain. The only specific claim of Wright's that Merlin discusses in the paper is that ...

On the basis of these results, Wright and her colleagues suggested that the induced and local hypermutability was an adaptive result of evolution by natural selection, that is, an adaptive response to adverse environmental conditions or, to be more precise, to amino acid starvation.

Merlin contends that this is not in fact an adaptive response even though it was a response that did have the effect of giving rise to an adaptation. Rather the adaptive mutation is simply a by product, due to the increased susceptibility of single stranded DNA, of the metabolic response to Leucine starvation, which is the upregulation of the Leu operon.

It would be interesting to see whether there was a specific increase in beneficial mutations of the Leu operon in a normal LeuB+ strain under starvation. The artificiality of the LeuB- experimental setup produces a possible mutation with such an overbearing selective advantage that one wonders what a more finely detailed approach might throw up. Sadly such experiments are considerably more challenging as with Lenski's long term evolutionary study.

TTFN,

WK


This message is a reply to:
 Message 117 by Percy, posted 09-26-2011 8:25 PM Percy has responded

Replies to this message:
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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 143 of 296 (635406)
09-29-2011 4:35 AM
Reply to: Message 123 by Percy
09-27-2011 7:13 AM


Re: Nitpicks and an interesting reference
But the big problem in this thread is that the IDists have one definition of "directed" while biology has another. The IDists see what they interpret as claims of directed evolution (in the biological sense) and interpret this as supportive of an intelligent designer.

To be fair to the IDists, Wright and Shapiro do frame their research as part of a narrative of overturning or radically altering the current evolutionary paradigm, so it isn't exactly hard to see how people already prone to false dichotomies see that automatically as supportive of their preferred 'theory'.

I think both Wright and Shapiro could do with the T-shirt carrying this slogan ...

The best alt text in the world for the best image in the world.

Come to think of it, I'd like that T-shirt too, in case any of you were wondering what to get me for Christmas.

TTFN,

WK


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 Message 123 by Percy, posted 09-27-2011 7:13 AM Percy has acknowledged this reply

Replies to this message:
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Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 149 of 296 (635805)
10-01-2011 8:00 PM
Reply to: Message 148 by shadow71
10-01-2011 7:20 PM


I don't read ... books (on biology).
Hi Shadow,

No, I haven't read Shapiro's books. I'm not really one for reading books on the biological sciences any more, although I read many as an undergrad, I much prefer the primary literature nowadays.

So as to what Shapiro say in his book I can't comment. In terms of what he has said in the published literature I think that I have already made my opinion clear in several threads and indeed in the post you just replied to here.

In the discursive elements of his papers and review he frequently goes well beyond what the data will actually support. He also seems to use very confusing non-standard terminology to try and shoehorn a whole series of processes into the category of intelligent, processes which I would argue really don't belong there.

I find it very unlikely that he is more circumspect and restrained in his book than he was in his papers.

TTFN,

WK


This message is a reply to:
 Message 148 by shadow71, posted 10-01-2011 7:20 PM shadow71 has not yet responded

    
Wounded King
Member (Idle past 2325 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 191 of 296 (643831)
12-12-2011 9:59 AM
Reply to: Message 189 by Kaichos Man
12-12-2011 6:43 AM


Re: Long time no contradict
But surely the conditions bringing about selection are random. Heat, cold, wet, dry, plentiful food, little food, intense competition, little competition, intense predation, little predation- the list is endless.

Hi Kaichos Man,

What you have produced here is a list of variables (temperature, humidity, predation, food supply), can you provide us with your rationale for considering them all to be random variables?

I'm a bit worried about where you must live that all of these factors are random from day to day. I have to say that I have yet to encounter a pride of lions coming down the street so little predation is pretty consistently the norm round my way. It must be hell going out without any idea of whether you are going to find a desert or a flood outside your door, but I guess it is only to be expected in a world where a capricious god turns the weather on and off at whim regardless of the natural order of the world.

Which, at the risk of annoying you, brings us back to the position of our old mate Kimura.

It so totally doesn't, at least not in relation to any position that Kimura actually held. His position as a popular source of misconceptions for creationists, perhaps.

TTFN,

WK


This message is a reply to:
 Message 189 by Kaichos Man, posted 12-12-2011 6:43 AM Kaichos Man has responded

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