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Author Topic:   Wright et al. on the Process of Mutation
Taq
Member
Posts: 7282
Joined: 03-06-2009
Member Rating: 3.9


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.


This message is a reply to:
 Message 242 by zi ko, posted 12-24-2011 9:54 AM zi ko has responded

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

  
Taq
Member
Posts: 7282
Joined: 03-06-2009
Member Rating: 3.9


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.


This message is a reply to:
 Message 236 by Wounded King, posted 12-23-2011 3:40 PM Wounded King has responded

Replies to this message:
 Message 258 by Wounded King, posted 01-04-2012 7:49 AM Taq has responded

  
Wounded King
Member (Idle past 1711 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 258 of 296 (646307)
01-04-2012 7:49 AM
Reply to: Message 257 by Taq
01-03-2012 6:20 PM


I am claiming that mutation rates in all genes that are upregulated in that environment will experience the same mutation rate

Well this isn't quite in line with the findings in the paper. I would agree that all the genes with the same expression level might be expected to experience the same mutation rate, all other things being equal, but the fact that a gene is upregulated in a response does not mean it will have the same level of expression as every other gene upregulated in the response.

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.

This is not the case of the bug focusing the mutation rate on one portion of one gene where the change is needed.
...
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.

I agree, and I don't think HereBeDragons or even Wright would disagree. I think we have reached here what is essentially a semantic issue whether we agree with Wright's position that ...

Wright writes:

The extent to which starvation regimen-dependent mutation rates are exclusively increased by derepression and ppGpp activation of a targeted operon appears to justify use of the word “specific”.

and further that ...

Whether hypermutation specific to the leu operon is described as being induced, enhanced, or directed by leucine starvation is arbitrary.

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

In the introduction she makes the distinction between different meanings of random in respect to evolution ...

Wright writes:

Neo-Darwinism holds that the spectrum of background mutations and the frequency with which they occur are random (undirected) with respect to selective conditions of the environment.

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.

TTFN,

WK


This message is a reply to:
 Message 257 by Taq, posted 01-03-2012 6:20 PM Taq has responded

Replies to this message:
 Message 259 by Taq, posted 01-04-2012 11:55 AM Wounded King has not yet responded

    
Taq
Member
Posts: 7282
Joined: 03-06-2009
Member Rating: 3.9


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.


This message is a reply to:
 Message 258 by Wounded King, posted 01-04-2012 7:49 AM Wounded King has not yet responded

  
zi ko
Member (Idle past 1235 days)
Posts: 578
Joined: 01-18-2011


Message 260 of 296 (648354)
01-15-2012 12:38 AM
Reply to: Message 256 by Taq
01-03-2012 12:21 PM


Re: Are there RANDOM MUTATIONS?
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.

But are not they closely related, as they both tent to preserve life? Of course this only is my belief based on obsevation. You can not see any tedency in nature. But this again is a belief.

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.

"Guided" does not mean "unmistakable". What is anyway your evidence that information is not guiding evolution? What is your evidence against the case of information is co-acting in instinct formation? If you don't bring any incotrovertible evidence about it , then your opinion is just a belief , as mine's is


This message is a reply to:
 Message 256 by Taq, posted 01-03-2012 12:21 PM Taq has responded

Replies to this message:
 Message 261 by Percy, posted 01-15-2012 8:15 AM zi ko has responded
 Message 265 by Taq, posted 01-17-2012 4:35 PM zi ko has responded

    
Percy
Member
Posts: 16339
From: New Hampshire
Joined: 12-23-2000
Member Rating: 2.4


Message 261 of 296 (648390)
01-15-2012 8:15 AM
Reply to: Message 260 by zi ko
01-15-2012 12:38 AM


Re: Are there RANDOM MUTATIONS?
zi ko writes:

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.

But are not they closely related, as they both tent to preserve life?

No. With random mutations, beneficial mutations are far outnumbered by those that are neutral or deleterious. In the absence of selection deleterious mutations would accumulate and reduce adaptation, the opposite of what you have chosen to call "preserving life."

Selection weeds out deleterious mutation and favors beneficial mutations, with the result that beneficial mutations tend to be preserved and spread throughout a population.

Without random mutation, selection would have no beneficial mutations to select.

Without selection, deleterious mutations would not be removed from a population.

"Guided" does not mean "unmistakable". What is anyway your evidence that information is not guiding evolution? What is your evidence against the case of information is co-acting in instinct formation? If you don't bring any incotrovertible evidence about it , then your opinion is just a belief , as mine's is

You have no evidence of the processes you claim exist, yet you want evidence that they don't exist? Do you also want evidence that unicorns don't exist?

--Percy


This message is a reply to:
 Message 260 by zi ko, posted 01-15-2012 12:38 AM zi ko has responded

Replies to this message:
 Message 262 by zi ko, posted 01-16-2012 11:06 PM Percy has responded

    
zi ko
Member (Idle past 1235 days)
Posts: 578
Joined: 01-18-2011


Message 262 of 296 (648609)
01-16-2012 11:06 PM
Reply to: Message 261 by Percy
01-15-2012 8:15 AM


Re: Are there RANDOM MUTATIONS?
You have no evidence of the processes you claim exist, yet you want evidence that they don't exist? Do you also want evidence that unicorns don't exist?

I show you two cases of guided mutations:
1.The relative lack of intermediate fossils during periods of greate environmental changes .
2.The rapid changes in finches beaks in Galapaguos islands in respond climate changes.
This message is a reply to:
 Message 261 by Percy, posted 01-15-2012 8:15 AM Percy has responded

Replies to this message:
 Message 263 by Larni, posted 01-17-2012 4:39 AM zi ko has responded
 Message 264 by Percy, posted 01-17-2012 7:56 AM zi ko has responded
 Message 266 by Taq, posted 01-17-2012 4:37 PM zi ko has responded

    
Larni
Member
Posts: 3952
From: Liverpool
Joined: 09-16-2005


Message 263 of 296 (648626)
01-17-2012 4:39 AM
Reply to: Message 262 by zi ko
01-16-2012 11:06 PM


Directed mutations.
I show you two cases of guided mutations:
1.The relative lack of intermediate fossils during periods of greate environmental changes .
2.The rapid changes in finches beaks in Galapaguos islands in respond climate changes.

You have asserted this but also have admitted that you have no evidence to support your assertion.

What conclusions are people to take from this?

I assert all the above is the result of Yahweh making thing evolove in the way Yahweh wants using psioinc enchantments. I too have no evidence to support this.

We are on an equal footing, no?


The above ontological example models the zero premise to BB theory. It does so by applying the relative uniformity assumption that the alleged zero event eventually ontologically progressed from the compressed alleged sub-microscopic chaos to bloom/expand into all of the present observable order, more than it models the Biblical record evidence for the existence of Jehovah, the maximal Biblical god designer.
-Attributed to Buzsaw Message 53

The explain to them any scientific investigation that explains the existence of things qualifies as science and as an explanation
-Attributed to Dawn Bertot Message 286

Well, Larni, let's say I much better know what I don't want to say than how exactly say what I do.


This message is a reply to:
 Message 262 by zi ko, posted 01-16-2012 11:06 PM zi ko has responded

Replies to this message:
 Message 267 by zi ko, posted 01-18-2012 12:06 AM Larni has responded

    
Percy
Member
Posts: 16339
From: New Hampshire
Joined: 12-23-2000
Member Rating: 2.4


Message 264 of 296 (648633)
01-17-2012 7:56 AM
Reply to: Message 262 by zi ko
01-16-2012 11:06 PM


Re: Are there RANDOM MUTATIONS?
zi ko writes:

I show you two cases of guided mutations:
1.The relative lack of intermediate fossils during periods of greate environmental changes .

You've examined mutations in fossils? Wow!

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

The changes in finch beaks in the Galapagos are not thought to be due to new mutations as far as we know. The expectation is that they're due to changing allele frequencies in certain genes. You can read a brief summary of the causes of finch beak changes at Molecular basis of beak evolution at Wikipedia. The cause of the changes in timing of development that affect beak size don't seem to have been tracked down to specific alleles.

But you've seem to have left out the issue I was addressing. You stated your belief that random mutations and selection both tend to preserve life. This is incorrect. Random mutations if allowed to spread unchecked will worsen adaptation. But random mutations filtered by natural selection so as to remove those that are ill-adaptive improves adaptation, or using your preferred term, "preserves life."

--Percy

Edited by Percy, : Slight clarification.


This message is a reply to:
 Message 262 by zi ko, posted 01-16-2012 11:06 PM zi ko has responded

Replies to this message:
 Message 268 by zi ko, posted 01-18-2012 12:37 AM Percy has responded

    
Taq
Member
Posts: 7282
Joined: 03-06-2009
Member Rating: 3.9


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?


This message is a reply to:
 Message 260 by zi ko, posted 01-15-2012 12:38 AM zi ko has responded

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: 7282
Joined: 03-06-2009
Member Rating: 3.9


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 . . . ?


This message is a reply to:
 Message 262 by zi ko, posted 01-16-2012 11:06 PM zi ko has responded

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

  
zi ko
Member (Idle past 1235 days)
Posts: 578
Joined: 01-18-2011


Message 267 of 296 (648727)
01-18-2012 12:06 AM
Reply to: Message 263 by Larni
01-17-2012 4:39 AM


Re: Directed mutations.
You have asserted this but also have admitted that you have no evidence to support your assertion.

What conclusions are people to take from this?

I assert all the above is the result of Yahweh making thing evolove in the way Yahweh wants using psioinc enchantments. I too have no evidence to support this.

We are on an equal footing, no?


What i meant is that i have no evidence by my own work. But there is evidence brought by Shapiro, wright, Yablonca ect, showing that information from environment guides evolution direction by direct action and not just indirectly through natural selection. Every day observations specially on instinct function and animal intelligence enhances this opinion. But it is still a belief.But you can choose to think that random mutations is the only resposible for them. It is again a matter of belief. You dont have any proofs about it.
This message is a reply to:
 Message 263 by Larni, posted 01-17-2012 4:39 AM Larni has responded

Replies to this message:
 Message 270 by Larni, posted 01-18-2012 3:26 AM zi ko has responded

    
zi ko
Member (Idle past 1235 days)
Posts: 578
Joined: 01-18-2011


Message 268 of 296 (648728)
01-18-2012 12:37 AM
Reply to: Message 264 by Percy
01-17-2012 7:56 AM


Re: Are there RANDOM MUTATIONS?
You've examined mutations in fossils? Wow!

Gould and others dit it.

The changes in finch beaks in the Galapagos are not thought to be due to new mutations as far as we know. The expectation is that they're due to changing allele frequencies in certain genes. You can read a brief summary of the causes of finch beak changes at Molecular basis of beak evolution at Wikipedia. The cause of the changes in timing of development that affect beak size don't seem to have been tracked down to specific alleles.


You seem to accept that there is more to evolution than genes, as Jablonca says. Mayby neural system and environment information? We are not sure yet. I agree!
But you've seem to have left out the issue I was addressing. You stated your belief that random mutations and selection both tend to preserve life. This is incorrect. Random mutations if allowed to spread unchecked will worsen adaptation. But random mutations filtered by natural selection so as to remove those that are ill-adaptive improves adaptation, or using your preferred term, "preserves life."


"Random" mutations and natural selection together with environmental information guiding "apparent "randomness in mutations lead to evolution. Deleterious or neutral mutations are inevitable by products of the process of preserving life. This the main moto. You prefer word fitness. I don't thing it expresses as clearly the real thing.

Edited by zi ko, : No reason given.


This message is a reply to:
 Message 264 by Percy, posted 01-17-2012 7:56 AM Percy has responded

Replies to this message:
 Message 271 by Percy, posted 01-18-2012 9:59 AM zi ko has responded

    
zi ko
Member (Idle past 1235 days)
Posts: 578
Joined: 01-18-2011


Message 269 of 296 (648730)
01-18-2012 1:16 AM
Reply to: Message 265 by Taq
01-17-2012 4:35 PM


Re: Are there RANDOM MUTATIONS?
How can you say that after 200+ posts where we discussed a paper that demonstrated those tendencies?

From a technical point of view Taq you are right. No one can prove tedency in nature. We can see only facts. But in spite of any deleterious mutatations the fact is that life is preserved;this is what nature is addressing at and this is what matters at the end. The existance of deleterious or neutral mutations does not cancel this tedency. Of course any body can choose the belief that fits to him.
My evidence that fitness is not guiding mutation is that the increased mutation rate was specific to ssDNA, not the leuB gene.

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".
I don't imply any Creator. I mean universal laws.
This message is a reply to:
 Message 265 by Taq, posted 01-17-2012 4:35 PM Taq has responded

Replies to this message:
 Message 278 by Taq, posted 01-19-2012 2:16 PM zi ko has responded

    
Larni
Member
Posts: 3952
From: Liverpool
Joined: 09-16-2005


Message 270 of 296 (648735)
01-18-2012 3:26 AM
Reply to: Message 267 by zi ko
01-18-2012 12:06 AM


Re: Directed mutations.
That is not what Shapiro says and you know it. You have had that pointed out to you many times.

No one believes random mutations are the only factor in evolution. This you have been told many times.

Why do you keep ignoring what you have been told?


The above ontological example models the zero premise to BB theory. It does so by applying the relative uniformity assumption that the alleged zero event eventually ontologically progressed from the compressed alleged sub-microscopic chaos to bloom/expand into all of the present observable order, more than it models the Biblical record evidence for the existence of Jehovah, the maximal Biblical god designer.
-Attributed to Buzsaw Message 53

The explain to them any scientific investigation that explains the existence of things qualifies as science and as an explanation
-Attributed to Dawn Bertot Message 286

Well, Larni, let's say I much better know what I don't want to say than how exactly say what I do.


This message is a reply to:
 Message 267 by zi ko, posted 01-18-2012 12:06 AM zi ko has responded

Replies to this message:
 Message 273 by zi ko, posted 01-18-2012 1:13 PM Larni has responded

    
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