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Author Topic:   Wright et al. on the Process of Mutation
Taq
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Posts: 8488
Joined: 03-06-2009


Message 234 of 296 (645126)
12-23-2011 1:27 PM
Reply to: Message 230 by zi ko
12-23-2011 11:15 AM


Re: beneficial mutations
As you believe that mutations are random and as i think mutations is the critical factor in evolution, you really believe man is a product of randomness.

Man is the product of natural selection which you have already admitted is non-random.


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Taq
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Posts: 8488
Joined: 03-06-2009


Message 235 of 296 (645127)
12-23-2011 1:32 PM
Reply to: Message 227 by Wounded King
12-23-2011 4:47 AM


But in the particular case from the Wright paper there is another important factor, the specific upregulation of Leu operon transcription in response to leucine starvation. Therefore the mutation rate has increased specifically for the leu operon locus, it hasn't increased for any the constitutively expressed house keeping genes.

The way I view it, the mutation rate in the leu operon has increased to the same level as seen in house keeping genes. Also, other genes not related to leu that are upregulated in that specific environment (e.g. glucose metabolism) will also see the same increase in mutation rate even though mutations in those genes are not needed.

But Wright's whole argument rests on it being a targeted increase. The leu operon specifically is being upregulated and therefore undergoing an increased level of mutation.

All upregulated genes are being targeted by this mechanism. It is specific to ssDNA, not the leu operon.


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Replies to this message:
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Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 254 of 296 (646142)
01-03-2012 12:04 PM
Reply to: Message 246 by zi ko
12-26-2011 12:17 AM


Re: Are there RANDOM MUTATIONS?
It does't make any difference.All have tried hard to preserve it.

In doing so, they produce mutations that are random with respect to fitness and survival.


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Taq
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Posts: 8488
Joined: 03-06-2009


Message 255 of 296 (646143)
01-03-2012 12:09 PM
Reply to: Message 247 by zi ko
12-26-2011 12:54 AM


Re: Are there RANDOM MUTATIONS?
As far as yoy accept universal laws you can not talk about random mutations.But you can use it knowing that nature allows this to happen in the frame of preserving life by it.

Random mutations also produce lethal mutations, and mutations that have no effect on fitness. On top of that, species go extinct all of the time.

Anything regards life is never random.

Where have you shown that the mutations described in the paper are not random with respect to fitness?

As life becomes more and more complex "randomness" is reduced as an evolutional factor.It is neural system and information traffic it takes its role.

Please cite data from the paper that supports your claims.


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Taq
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Posts: 8488
Joined: 03-06-2009


Message 256 of 296 (646146)
01-03-2012 12:21 PM
Reply to: Message 242 by zi ko
12-24-2011 9:54 AM


Re: Are there RANDOM MUTATIONS?
They are not the same. Try to replace with one another in different expressions and you will realise it.

I have. They are the same.

Any way for the sake of conversation let us accept they are the same.Mutations then are random to life preservation.So life has not any tedency to preserve itself.

You are using a bait and switch. Mutations are random with respect to life's preservation. Mutations will occur that are lethal, have no effect on survival, or increase survival for a given individual. That is a fact. The same process produces all three types of mutations. However, the reproductive success of a given individual is NOT random with respect to fitness. That is the bait and switch. You want to switch freely between the randomness of mutations and the non-random nature of reproductive success. They are different things. One is not the other.

Organisms with higher fitness have a tendency to have more offspring in the next generation. This, in no way, negates the observation that mutations are random with respect to fitness.

Then how do you explain the "repairing mechanisms" inside cells biologists talk about?

What needs to be explained?

You must note the word about in my answer.Mistakes is a common thing in nature.What that could mean?

Ahh, so if this process produces lethal mutations then it is a "mistake". If it produces beneficial mutations then it is "guided". Sorry, but this is a clear and obvious bias. The same process produces both.

Nature has its own way.You can't judge it. The real question is if we believe or not it has the tedency and the ability to preserve itself.

I see no tendency. Nature is indifferent to the presence of life. Look at all of the major extinction events in Earth's history. Look at all of the planets without life in our own solar system. Life is probably the exception in our Universe, not the rule. There is no law in nature the requires that life be preserved. None.

Edited by Taq, : No reason given.


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Replies to this message:
 Message 260 by zi ko, posted 01-15-2012 12:38 AM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 257 of 296 (646234)
01-03-2012 6:20 PM
Reply to: Message 236 by Wounded King
12-23-2011 3:40 PM


Ok, so what genes are upregulated in response to leucine starvation? Are you claiming that all housekeeping genes are?

I am claiming that mutation rates in all genes that are upregulated in that environment will experience the same mutation rate, even those genes where a mutation is not needed.

You seem to be redefining 'upregulated' to mean simply expressed.

For the purposes of this mechanism, it is one in the same. Genes that are actively transcribed are seeing an increase in mutation rate due to the ssDNA state of that gene compared to genes that are not actively transcribed. All that matters is whether or not that gene is being transcribed. If the leu operon were upregulated in non-stringent conditions it would still see the same mutation rate in the stringent conditions if the transcription levels were the same. If the plates also contained glucose then the genes in that pathway would also see an increase in their mutaiton rate even though they are functioning just fine.

I don't see a problem with other genes involved in the response being upregulated, after all Wright's argument is that genes upregulated in a response are likely to be the best targets for producing novel beneficial mutations since they should be the most relevant to the given stress. It just so happens that in the specific experimental setup in the paper there is a very limited repertoire of potential mutations that will rescue the leuB- mutant. Whether Wright would actually see it this way I don't know, I've said before that I think she exaggerates a number of things, and one of them is the specificity of the response.

I have used the analogy of poor people buying more lottery tickets than rich people. It applies here. It is a good overall strategy, but it doesn't change the fact that the mutations are still random with respect to fitness just like the lottery results are random with respect to the tickets. You are still going to see mutations in genes where they are not needed, including lethal mutations. This is not the case of the bug focusing the mutation rate on one portion of one gene where the change is needed.

As far as I can see the specificity resides in the specific amino acid biosynthesis operon that is turned on, along with all the other stringent response effects. So a mutation in the leu Operon becomes more likely than one in trp.

It is my opinion that it is specific to all DNA that is actively transcribed which is a much larger pool than the specific amino acid biosynthesis operon.

There is certainly some redistribution of the mutational spectrum across the genome, whether it favours beneficial mutations arising in the population is another question, certainly in the paper a large number of beneficial mutations do occur in the population above the mutation/reversion rate if we accept the mutation/reversion rates will be comparable between unstarved and starved relA populations in line with the expression levels.

I view it as certain portions of the genome getting more rolls of the dice. It still doesn't change the fact that the rolls are random. And also like gambling, some are going to end up worse off than when they started due to lethal mutations in previously functional genes.


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Replies to this message:
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Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 259 of 296 (646359)
01-04-2012 11:55 AM
Reply to: Message 258 by Wounded King
01-04-2012 7:49 AM


So if for example LeuB expression was to see a much more substantial expression level in response than the majority of other responsive genes we might expect it to similarly have a more substantially elevated mutation rate. It gets a bit tricky here in that so often upregulation is described in terms of the fold change in expresssion while for the mechanisms in Wright's paper the actual absolute expression level seems to be the key thing, so a gene seeing a 100 or 1000 fold increase may still have an absolute expression level well below one that had a much more moderate 2-5 fold increase.

The authors seemed to have addressed this when they replaced the wild type leu operon promoter with an IPTG inducible promoter. This way they could control expression independently of leucine starvation. However, they found that this promoter was not as effecient in producing mutations as the native promoter. They hypothesize that the ppGpp mechanism pauses RNA polymerase. From the paper:

"This suggests that ppGpp may be affecting the concentration of ssDNA by some mechanism related to and in addition to its effect on transcription. Work in progress concerns leuB mRNA turnover, as well as investigations into the effect of ppGpp on pausing of RNA polymerase (21), which could increase the concentration of ssDNA and mutation rates at specific pause sites."

So I will agree that upregulation alone can not completely explain the increased mutation rate in leuB. There seems to be an additional mechanism in play (e.g. RNA polymerase pausing, mRNA folding, DNA hairpins).

Wright claims the response is specific because the the amino acid synthesis operon induced is specific to the particular starvation the bacterium is experiencing.

IMHO, Wright et al. are overselling it. I will state that what they did find is important and well worth publication. At the same time, I can not call this a specific mutational mechanism. There is specificity at the trascriptional level when focusing just on the leuB operon, but this specificity goes away when you look at the entire genome and how mutations will be spread across actively transcribed genes.

It might be worth putting this paper in context with early work on "adaptive mutations" where there was an increase in lac- reversions. This was due to a slightly different mechanism that involves the SOS response. In this case, the increased mutation rate is due to upregulation of error prone polymerases (DinB IIRC) and an increase in recombination rates. The presence of lactose did not directly increase the mutation rate of the lac operon. Instead, selection was the only enrichment step for producing these revertants (usually through a combination of gene duplication and subsequent mutation of the duplications). In this view, Wright et al. have found a mechanism that is more specific than previous adaptive mutations. When put in this context, the lueB- reversion is more specific. However, when stripped of this context it can be misunderstood. If I were a reviewer I would have required them to include this context so that the reader would better understand what specificity means in this case.

I think she has made a reasonable case that specific environmental conditions can produce specific changes in expression which will affect the frequency distribution of mutations at the regulated genes. the mutation rate in the housekeeping genes should continue as it was previously, unaffected by the whole process.

That is certainly the best sales pitch that the authors can use, and it is a fair description of the mechanisms. The problem is when others take it that extra step and claim that this falsifies the concept of random mutations (with respect to fitness). To be fair, there are a lot of subtleties in this paper that are not obvious to someone new to the subject.

To sum up what I have said before, this is a noteworthy paper. I am not discounting its importance. However, it falls short of non-random mutation in my estimation due to the fact that the mutation mechanism is not specific to the leuB- operon. Instead, it is specific to ssDNA.

Edited by Taq, : No reason given.


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Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 265 of 296 (648693)
01-17-2012 4:35 PM
Reply to: Message 260 by zi ko
01-15-2012 12:38 AM


Re: Are there RANDOM MUTATIONS?
But are not they closely related

I would argue that they are not. They are two very different mechanisms.

You can not see any tedency in nature. But this again is a belief.

How can you say that after 200+ posts where we discussed a paper that demonstrated those tendencies?

What is anyway your evidence that information is not guiding evolution?

My evidence that fitness is not guiding mutation is that the increased mutation rate was specific to ssDNA, not the leuB gene.

If you don't bring any incotrovertible evidence about it , then your opinion is just a belief , as mine's is

I have brought evidence to bear. Where is yours?


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Replies to this message:
 Message 269 by zi ko, posted 01-18-2012 1:16 AM Taq has responded
 Message 291 by zi ko, posted 02-02-2012 9:33 AM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 266 of 296 (648695)
01-17-2012 4:37 PM
Reply to: Message 262 by zi ko
01-16-2012 11:06 PM


Re: Are there RANDOM MUTATIONS?
I show you two cases of guided mutations:
1.The relative lack of intermediate fossils during periods of greate environmental changes .

So what are these mutations?

2.The rapid changes in finches beaks in Galapaguos islands in respond climate changes.

And these mutations are . . . ?


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Replies to this message:
 Message 274 by zi ko, posted 01-18-2012 1:25 PM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 278 of 296 (648954)
01-19-2012 2:16 PM
Reply to: Message 269 by zi ko
01-18-2012 1:16 AM


Re: Are there RANDOM MUTATIONS?
No one can prove tedency in nature.

The Wright et al. paper demonstrates that we can.

But in spite of any deleterious mutatations the fact is that life is preserved;

Where did you show that? If Wright et al. used a population of just 100 bacteria they would not have been preserved given the fact that the beneficial mutation only occurs once in every 500 million divisions.

The existance of deleterious or neutral mutations does not cancel this tedency.

I guess you have never heard of the multiple mass extinctions that have occurred in Earth's history? The Permian extinction saw more than 90% of species disappearing from the face of the Earth.

Again your evidence maby it is misinterpreted by you.You have to prove, at least for yourself, there is not any tedency behind these "facts".

That is exactly what I have done in this thread. The data from the paper demonstrates that the increased mutation rate is specific to ssDNA, not the leuB gene. If you are going to claim that I am misrepresenting the findings then you had better show how I am misrepresenting it.


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 Message 269 by zi ko, posted 01-18-2012 1:16 AM zi ko has responded

Replies to this message:
 Message 280 by zi ko, posted 01-28-2012 11:26 AM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 279 of 296 (648955)
01-19-2012 2:18 PM
Reply to: Message 274 by zi ko
01-18-2012 1:25 PM


Re: Are there RANDOM MUTATIONS?
The increased rate of mutations that led to rapid evolution renders them directed .

Again, I have shown that this is not true with reference to the Wright et al. paper. It is an increase in the random mutation rate, not directed mutagenesis.


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Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 287 of 296 (650348)
01-30-2012 12:53 PM
Reply to: Message 280 by zi ko
01-28-2012 11:26 AM


Re: Are there RANDOM MUTATIONS?
You still have to prove that the same mechanisms or principles apply to higher types of life.

What I can say is that mutations are random with respect to fitness in the species that have been studied. You are trying to claim that mutations are NOT random with respect to fitness, and yet you can not point to a single study where this is the case.

Also that the "obvious" lack o tedency on this experiment was not the result of nuture's "knowledge" that tedency on that particular case was not necessary; so the tedency to life preservation was not clearly evident, but it was there.

Then supply the evidence from the paper that it was there.

But what if nature can "know"that 500 million divisions is a usual happening and could rely on this fact?

What if it didn't?

But in spite of this life managed to preserve itself so successfuly.

But many species did not.


This message is a reply to:
 Message 280 by zi ko, posted 01-28-2012 11:26 AM zi ko has responded

Replies to this message:
 Message 288 by zi ko, posted 02-01-2012 1:04 AM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 290 of 296 (650607)
02-01-2012 11:37 AM
Reply to: Message 288 by zi ko
02-01-2012 1:04 AM


Re: Are there RANDOM MUTATIONS?
So regarding the issue of tendency for life preservation we are equally footed.

No, we aren't. I have an evidenced mechanism where life is producing mutations that are random with respect to fitness. You claim that they are guided by life's knowledge, but you have no evidence for any mechanism by which this happens. My claims are based on evidence. Your claims are based on wishful thinking.

It is a matter of belief.

No, it is a matter of evidence. I have it. You don't.


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Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 292 of 296 (650708)
02-02-2012 11:10 AM
Reply to: Message 291 by zi ko
02-02-2012 9:33 AM


Re: Are there RANDOM MUTATIONS?
I din't understand it. What do you mean by "those tendencies"?

The tendency for mutations to be random with respect to fitness. Even more specifically, the tendency for single stranded DNA to accumulate more random mutations than double stranded DNA in E. coli.

The question is quite different.

Such a statement is usually followed by an explanation of how it is different.


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Replies to this message:
 Message 293 by zi ko, posted 03-14-2012 2:45 AM Taq has responded

  
Taq
Member
Posts: 8488
Joined: 03-06-2009


Message 295 of 296 (655932)
03-15-2012 12:39 AM
Reply to: Message 293 by zi ko
03-14-2012 2:45 AM


Re: Are there RANDOM MUTATIONS?
I think "respect to life preserving" is more appropriate, as wider and more representative term.

The chances of life being preserved is defined by the random mutation rate. I really don't see how this helps resolve anything. We are right back to the probability of a specific mutation occuring and how it relates to fitness.

In the case of this paper, there is a 1 in 500 million chance of a bacterium getting the needed mutation. This probability changes as a function of the state of the DNA, either single stranded or double stranded. The probability is not affected by the NEEDS of the organism which makes the mutation random with respect to fitness. If the needed mutation were in a gene that was not actively transcribed then this mechanism would lower the chances of life being preserved. This same mechanism also increases the deleterious mutation rate in important and vital genes that are actively transcribed.


This message is a reply to:
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