Understanding through Discussion


Welcome! You are not logged in. [ Login ]
EvC Forum active members: 114 (8796 total)
Current session began: 
Page Loaded: 10-22-2017 3:05 PM
336 online now:
dwise1, Faith, halibut, PaulK, RAZD, ringo (6 members, 330 visitors)
Chatting now:  Chat room empty
Newest Member: jaufre
Upcoming Birthdays: willietern
Happy Birthday: Flyer75
Post Volume:
Total: 821,049 Year: 25,655/21,208 Month: 1,282/2,338 Week: 39/364 Day: 39/57 Hour: 1/6

Announcements: Reporting debate problems OR discussing moderation actions/inactions


Thread  Details

Email This Thread
Newer Topic | Older Topic
  
RewPrev1
...
1516
17
181920Next
Author Topic:   Wright et al. on the Process of Mutation
Percy
Member
Posts: 16036
From: New Hampshire
Joined: 12-23-2000
Member Rating: 3.0


Message 241 of 296 (645199)
12-24-2011 8:59 AM
Reply to: Message 240 by Chuck77
12-24-2011 6:34 AM


Re: beneficial mutations
Chuck77 writes:

Although this isn't the thread for it, but I took your analogy to infer a desinger when you mentioned factory.

I'm an unlikely person to infer a designer. The factory producing gumdrops of all colors is analogous to reproduction producing mutations of all types. The machine on the end selecting for red gumdrops is analogous to natural selection selecting for good adaptation to the environment. A random assortment of colors becomes only red ones, a random assortment of mutations becomes only adaptive ones.

So when we look at the factory's output and see only red ones we are unlikely to conclude that the manufacturing process, considered in its entirety (random assortment of colored gumdrops plus the "select red" machine), is random. And when we see only adaptive mutations we are unlikely to conclude that the evolutionary process, considered in its entirety (random mutation plus natural selection) is random with respect to adaptation.

Of course, the analogy is just to illustrate why evolutionists do not consider evolution a random process with respect to adaptation. It's not intended as an illustration of evolution itself.

--Percy


This message is a reply to:
 Message 240 by Chuck77, posted 12-24-2011 6:34 AM Chuck77 has acknowledged this reply

    
zi ko
Member (Idle past 1180 days)
Posts: 578
Joined: 01-18-2011


Message 242 of 296 (645205)
12-24-2011 9:54 AM
Reply to: Message 233 by Taq
12-23-2011 1:26 PM


Re: Are there RANDOM MUTATIONS?
Yes mutations are random to fitness but not random to life's preservation.

Those are the same thing.


They are not the same. Try to replace with one another in different expressions and you will realise it.Why use then fitness and not life preservation?Life preservation has a much wider meaning.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.It is just ahuman fallacious impression, in spite of all common knowledge. Then how do you explain the "repairing mechanisms" inside cells biologists talk about?

Humans are born with mutations that cause lethal diseases that kill children before they ever reach adulthood. You are clearly wrong.

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

The 2 out of 1 billion is the same rate whether there are a billion bacteria or just 10. Again, you are clearly wrong.

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.

Edited by zi ko, : No reason given.


This message is a reply to:
 Message 233 by Taq, posted 12-23-2011 1:26 PM Taq has responded

Replies to this message:
 Message 244 by Dr Adequate, posted 12-24-2011 10:30 AM zi ko has responded
 Message 245 by Percy, posted 12-24-2011 11:55 AM zi ko has responded
 Message 256 by Taq, posted 01-03-2012 12:21 PM zi ko has responded

    
zi ko
Member (Idle past 1180 days)
Posts: 578
Joined: 01-18-2011


Message 243 of 296 (645208)
12-24-2011 10:20 AM
Reply to: Message 240 by Chuck77
12-24-2011 6:34 AM


Re: beneficial mutations
I think zi ko believes there is a designer involved.
You propably took me wrong. I believe disigner is nature itself with its universal laws.
This message is a reply to:
 Message 240 by Chuck77, posted 12-24-2011 6:34 AM Chuck77 has not yet responded

    
Dr Adequate
Member
Posts: 15962
Joined: 07-20-2006
Member Rating: 5.0


Message 244 of 296 (645212)
12-24-2011 10:30 AM
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.Why use then fitness and not life preservation?Life preservation has a much wider meaning.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.It is just ahuman fallacious impression, in spite of all common knowledge. Then how do you explain the "repairing mechanisms" inside cells biologists talk about?

Living things have some methods of preserving their lives but not others. This is so obvious that I feel embarrassed for you that it's necessary to point it out.


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 246 by zi ko, posted 12-26-2011 12:17 AM Dr Adequate has responded

  
Percy
Member
Posts: 16036
From: New Hampshire
Joined: 12-23-2000
Member Rating: 3.0


Message 245 of 296 (645221)
12-24-2011 11:55 AM
Reply to: Message 242 by zi ko
12-24-2011 9:54 AM


Re: Are there RANDOM MUTATIONS?
zi ko writes:

Yes mutations are random to fitness but not random to life's preservation.

Those are the same thing.

They are not the same.

They're not precise synonyms, but they're based upon the same principle, and random mutations have the same effect on both. A random mutation that is deleterious with respect to fitness is also deleterious with respect to "life's preservation." Same for beneficial mutations. If you don't think this is true then name a random mutation that would be beneficial for one and deleterious for the other.

Mutations then are random to life preservation. So life has not any tendency to preserve itself.

You're forgetting selection again. Life produces many offspring, they compete for limited resources, the best succeed in contributing offspring to the next generation. Life that by the luck of the draw possess beneficial mutations will contribute more offspring to the next generation, and gradually those beneficial mutations will spread throughout the population.

The real question is if we believe or not it has the tendency and the ability to preserve itself.

Life has the ability to adapt to changing environments through the processes of mutation and natural selection.

Is this discussion about whether evolution is random related to the topic?

--Percy


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 247 by zi ko, posted 12-26-2011 12:54 AM Percy has responded

    
zi ko
Member (Idle past 1180 days)
Posts: 578
Joined: 01-18-2011


Message 246 of 296 (645321)
12-26-2011 12:17 AM
Reply to: Message 244 by Dr Adequate
12-24-2011 10:30 AM


Re: Are there RANDOM MUTATIONS?
Living things have some methods of preserving their lives but not others.

It does't make any difference.All have tried hard to preserve it.
This message is a reply to:
 Message 244 by Dr Adequate, posted 12-24-2011 10:30 AM Dr Adequate has responded

Replies to this message:
 Message 249 by Dr Adequate, posted 12-26-2011 12:32 PM zi ko has not yet responded
 Message 254 by Taq, posted 01-03-2012 12:04 PM zi ko has not yet responded

    
zi ko
Member (Idle past 1180 days)
Posts: 578
Joined: 01-18-2011


Message 247 of 296 (645322)
12-26-2011 12:54 AM
Reply to: Message 245 by Percy
12-24-2011 11:55 AM


Re: Are there RANDOM MUTATIONS?
Life has the ability to adapt to changing environments through the processes of mutation and natural selection.


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.Anything regards life is never random. Even "randomness" is not really random.Only in nonorganic world you can.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.

Edited by zi ko, : No reason given.


This message is a reply to:
 Message 245 by Percy, posted 12-24-2011 11:55 AM Percy has responded

Replies to this message:
 Message 248 by Percy, posted 12-26-2011 8:18 AM zi ko has not yet responded
 Message 255 by Taq, posted 01-03-2012 12:09 PM zi ko has not yet responded

    
Percy
Member
Posts: 16036
From: New Hampshire
Joined: 12-23-2000
Member Rating: 3.0


Message 248 of 296 (645333)
12-26-2011 8:18 AM
Reply to: Message 247 by zi ko
12-26-2011 12:54 AM


Re: Are there RANDOM MUTATIONS?
Hi Zi Ko,

What we've been saying is that mutations are random with respect to adaptation. Natural selection, which resists the propagation of ill-adaptive mutations, is not random with respect to adaptation.

But now you've dropped into declarative mode and aren't even pretending to be interested in the
topic. Discussion of neural systems and information should have its own thread. I see that your thread proposal from 12/16 hasn't drawn a moderator response yet, so I'll look at it now.

--Percy


This message is a reply to:
 Message 247 by zi ko, posted 12-26-2011 12:54 AM zi ko has not yet responded

    
Dr Adequate
Member
Posts: 15962
Joined: 07-20-2006
Member Rating: 5.0


Message 249 of 296 (645348)
12-26-2011 12:32 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.

And yet their efforts have not led to them being able to perform genetic engineering on themselves any more than it has led to them developing time travel or learning to violate the law of conservation of energy, useful though these abilities might be.


This message is a reply to:
 Message 246 by zi ko, posted 12-26-2011 12:17 AM zi ko has not yet responded

  
herebedragons
Member
Posts: 1413
From: Michigan
Joined: 11-22-2009
Member Rating: 2.2


Message 250 of 296 (645471)
12-27-2011 8:07 AM
Reply to: Message 226 by Taq
12-23-2011 1:50 AM


They are arguing just that. However, they fail miserably IMHO.

I’m not sure I agree that they have failed miserably. Maybe overstated the significance of their findings.

I do agree that only 1 reversion in 500 million is not really suggestive of a “directed” mutation. But I am also not sure at what level it could be considered “directed”. Would it need to be 50%? Or 25%, 10%? Seems kind of arbitrary. It may be a subjective rather than objective observation.

At the end of the day this is no different than a beggar on the corner getting an extra ten dollars to spend on the lottery. The non-random increase in the purchase of tickets in no way makes the actual lottery drawing non-random with respect to financial need.

But, if I sought out only those beggars who were starving and close to starving to death and gave 500 million of them each a lottery ticket, it would surely increase the likelihood that I would save the life and improve the lifestyle of several beggars. That would be targeted. So, while the drawing itself may still be random, the distribution of the “chances” would not be but would be specifically targeted to those that needed it most.

I cited DNA gyrase as one of those genes, and it serves as a good example ... So, the very mechanism that increases the rate of beneficial mutations in the lueB gene also increases the neutral and lethal mutations in vital housekeeping genes. By definition, this is random mutation. It is an increase in changes that are random with respect to fitness.

There was no data regarding the mutation rate of any housekeeping genes in this paper (and as I said, I think that would be good data to have) So it is difficult to interpret what is going on in other areas of the genome. Does mutation rate increase in all genes or merely in the targeted genes? It is at least implied by the authors that the increase is targeted to specific genes. There is no product being made that is a mutagen that would increase overall mutation rate.

The only mechanism mentioned for increasing mutation rate is increased transcription (and in fact, the lueB gene seems to be stuck in the “on” position). Would transcription of DNA gyrase (for example) increase? In fact, Wright says that during starvation ppGpp inhibits the synthesis of DNA, rRNA, nucleotides and phospholipids and therefore arrests cell division. So many of the housekeeping genes would actually be down regulated. She also states that

quote:
ppGpp activates only those genes that are specifically derepressed by the type of starvation imposed

So the target of increased transcription is specific and should not affect other genes operating at constituent levels. There would continue to be mutations in other genes, but only at background levels. I think the whole point is that the genes that needed the mutation became the most likely targets while the others were somewhat protected from mutation. A balance between getting the needed mutation and preventing deleterious mutations.

Another thing I found interesting was the amount of mRNA transcribed by the leuB gene during starvation. LeuB mRNA was about 6 times more abundant when starved for leucine than when grown to log phase. (fig 2.) Since mRNA can be translated at the same time it is being transcribed, and by several ribosomes simultaneously it appears to be “fishing”. Generate large amounts of mRNA until something works. What are the mRNA levels in a leuB+ strain when starving? Another key piece of evidence to show that this is indeed increased transcription and hypermutation, I believe.

Finally, I had trouble understanding how the mechanisms the authors proposed in this paper, ssDNA vulnerability and RNA polymerase stalling, could induce hypermutability. Wright discusses the mechanisms here that may account for targeted mutations and increased mutation rates. (You may have already seen this, WK pointed it out earlier in this thread) I think they are quite plausible. The vulnerability of ssDNA comes from secondary structures and the resultant unpaired and mispaired bases in the stem-loop system. The second mechanism described is localized supercoiling and, again, the secondary structures that form (RNAP stalling may be a consequence of supercoiling, but is not really discussed in detail).

I would say that based on this paper and supporting literature, there is evidence that some mutations are directed as they apply to fitness. Maybe it is just a matter of semantics, but perhaps directed is inappropriate. Perhaps “guided” would be a better term. While the mutations themselves are random, they are “guided” to some genes or areas that are more likely to provide a benefit to the organism. Difficult to draw a solid conclusion based on one study, but more work could be done on this; I would think it could have considerable implications in human disease.

HBD


This message is a reply to:
 Message 226 by Taq, posted 12-23-2011 1:50 AM Taq has not yet responded

  
herebedragons
Member
Posts: 1413
From: Michigan
Joined: 11-22-2009
Member Rating: 2.2


Message 251 of 296 (645472)
12-27-2011 8:18 AM
Reply to: Message 236 by Wounded King
12-23-2011 3:40 PM


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 believe she is claiming that the leuB- mutation is characterized as a C-to-T transition at aa286 resulting in a serine-to-leucine substitution. So a very specific mutation. She also claims that 80% of revertants were true revertants, which I take to mean they undid the aforementioned mutation. So, as you said, a very limited repertoire of potential mutations that rescue the leuB- mutant.

In her follow up paper, A Biochemical Mechanism for Nonrandom Mutations ..., she asserts that unpaired and mispaired bases in stem-loop structures are more likely to undergo mutation. Fig 1C shows such a structure, but I don’t think it is specific to leuB but merely illustrative of her hypothesis. However, mutation (1) supposedly represents the C-to-T mutation of interest.

So, why is it you think the specificity of the response is exaggerated?

I would say her claims of upsetting neo-Darwinism and going against the established paradigm are exaggerated. And maybe she has jumped the gun on claims of “directed mutations” based on these limited studies. But this particular response does seem to be quite specific. It remains to be seen if this applies to other operons as well.

HBD

BTW, I am just trying to clarify your objections, not argue my particular point.


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 252 by Wounded King, posted 12-27-2011 11:59 AM herebedragons has responded

  
Wounded King
Member (Idle past 1655 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 252 of 296 (645493)
12-27-2011 11:59 AM
Reply to: Message 251 by herebedragons
12-27-2011 8:18 AM


herebedragons writes:

I believe she is claiming that the leuB- mutation is characterized as a C-to-T transition at aa286 resulting in a serine-to-leucine substitution. So a very specific mutation. She also claims that 80% of revertants were true revertants, which I take to mean they undid the aforementioned mutation. So, as you said, a very limited repertoire of potential mutations that rescue the leuB- mutant.

I don't think it is quite as restrictive as you make out. Looking at the paper Wrights gives as a reference for that 80% figure (Wright and Minnick, 1997) we find a more detailed analysis ...

Wright and Minnick writes:

Of these revertants, 36 were found to contain nucleotide substitutions that would result in a serine (wild type), valine or methionine at amino acid residue 286 of LeuB, and nearly all of them exhibited generation times similar to wild type. Seventeen of the analysed revertants were found to be suppressors that retained the encoded leucine at residue 286. The majority of the suppressor mutants exhibited generation times that were significantly longer than wild type.

The paper defines true revertants as those which produce an amino acid substitution at aa286 for one of 3 different amino acids. Only those which produced serine would be the exact reverse mutation to the original C-T transition. In fact that was slightly edged out by a T-G transition at a different nucleotide which substituted a valine at aa286.

So, why is it you think the specificity of the response is exaggerated?

Because LeuB is not the only gene upregulated by the stringent response during leucine starvation. So while a specific small spectrum of mutations may be capable of producing revertants, and an even smaller set of producing what Wright calls 'true' revertants, there is no control to see what other mutations are being produced in other genes being upregulated.

By focussing on such a specific target and ignoring the possibility of any other elevated mutation rates in the rest of the responsive genome Wright effectively exaggerates the specificity of the response. The reverting mutation may be highly specific, but without a better characterisation of the change in mutation rates at a wider sample of upregulated loci we can't really say how specific the response was.

If all of the ~300 genes upregulated as part of the stringent response have increased mutation rates (about 8% of the E. coli genome) then does that constitute a sound basis for a claim of directed mutation? And more to the point does if form as good a basis for a claim of mutation being directed towards the LeuB gene?

In her discussion in the original paper from the OP Wright says ...

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”.

But how exclusive is this increase? In reality it appears only to be 'exclusive' to the exclusion of the other amino acid biosynthesis operons.

Wright is essentially claiming that everything else is equal in the stringent response whichever amino acid the population is being starved for so the only difference in those responses is in the resulting upregulated operon. At least that is how I interpret it.

TTFN,

WK

Edited by Wounded King, : No reason given.


This message is a reply to:
 Message 251 by herebedragons, posted 12-27-2011 8:18 AM herebedragons has responded

Replies to this message:
 Message 253 by herebedragons, posted 12-27-2011 7:56 PM Wounded King has acknowledged this reply

    
herebedragons
Member
Posts: 1413
From: Michigan
Joined: 11-22-2009
Member Rating: 2.2


Message 253 of 296 (645546)
12-27-2011 7:56 PM
Reply to: Message 252 by Wounded King
12-27-2011 11:59 AM


I don't think it is quite as restrictive as you make out.

Yea, I didn't realize they were defining true revertants to even include those that substituted valine or methionine. I assumed true revertants were exact reversals. My misunderstanding or perhaps an exaggeration on the part of the author

By focussing on such a specific target and ignoring the possibility of any other elevated mutation rates in the rest of the responsive genome Wright effectively exaggerates the specificity of the response. The reverting mutation may be highly specific, but without a better characterisation of the change in mutation rates at a wider sample of upregulated loci we can't really say how specific the response was.

Agreed. This was basically my criticism . Not enough information regarding background and responses at other genes. She only reported the data that supported her hypothesis.

Thanks

HBD


This message is a reply to:
 Message 252 by Wounded King, posted 12-27-2011 11:59 AM Wounded King has acknowledged this reply

  
Taq
Member
Posts: 7196
Joined: 03-06-2009
Member Rating: 3.1


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.


This message is a reply to:
 Message 246 by zi ko, posted 12-26-2011 12:17 AM zi ko has not yet responded

  
Taq
Member
Posts: 7196
Joined: 03-06-2009
Member Rating: 3.1


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.


This message is a reply to:
 Message 247 by zi ko, posted 12-26-2011 12:54 AM zi ko has not yet responded

  
RewPrev1
...
1516
17
181920Next
Newer Topic | Older Topic
Jump to:


Copyright 2001-2015 by EvC Forum, All Rights Reserved

™ Version 4.0 Beta
Innovative software from Qwixotic © 2017