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Author Topic:   Wright et al. on the Process of Mutation
Taq
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Posts: 7196
Joined: 03-06-2009
Member Rating: 3.1


(2)
Message 226 of 296 (645083)
12-23-2011 1:50 AM
Reply to: Message 225 by herebedragons
12-22-2011 8:12 PM


1. The authors do seem to be arguing for at least a form of directed mutation.

I agree. They are arguing just that. However, they fail miserably IMHO. What they are arguing is analogous to a poor person buying more lottery tickets. They argue that since the the poor person increases their odds of winning the lottery by buying more lottery tickets that the lottery is no longer random. I see no reason to agree with them. Do you?

I am unclear as to what their actual hypothesis was in this paper. It seems to be derepression-induced hypermutation being the link between mutations and environmental stress. Is that a fair summary of their position?

That is a fair summary. The result of this mechanism is an increase in random mutations, and a higher rate of random mutations within regions of the genome that are actively transcribed. This means that there is an increase in mutations within the leuB- gene which increases the rate of beneficial mutations in an environment which lacks leucine. At the same time, this also increases the rate of mutations in important housekeeping genes that were functioning just fine in the given environment. This mechanism increases the beneficial, neutral, and detrimental mutation rate based on the rate of gene regulation, not on what is or is not beneficial to the organism in a given environment. If the situation were different, there could be a case where the needed beneficial mutation would be found in a gene that was downregulated in a given environment. This would mean that this mechanism could just as well work against the "directed" evolution of the organism.

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.

I did not see where you did this. Not that I doubt that the premise would be true, but I don’t think the data in the paper supports rates of deleterious or neutral mutations.

That is a very fair criticism of my post. The evidence for what I stated is very subtle and hard to understand unless you have a background in molecular biology. My lottery analogy is applicable in this case.

The support for my argument is the experiments with the lac promoter. They removed the wild type (i.e. normal) promoter from the lueB gene and replaced it with a lac promoter that could be turned off and on with the addition of exogenous chemicals (I presume that they are using IPTG). What they found is that they could increase the mutation rate in the lueB gene by adding the chemical that turned on the lac promoter. This indicates that the increase in the beneficial mutation rate is tied to gene regulation, that is the ssDNA condition of that part of the genome. This means that any gene that is being actively transcribed is going to see an increase in the mutation rate. This includes vital housekeeping genes.

I cited DNA gyrase as one of those genes, and it serves as a good example. In the experiment, the DNA gyrase gene worked just fine. There was no environmental pressure for the gyrase gene to change. From my own work, I know that any living cell is always actively copying this gene from DNA to RNA. That is why they call it a housekeeping gene. This means that this gene is always incurring more mutations than genes that are not actively being transcribed from DNA to RNA. The only result of mutating this gene in an environment that does not need a change in DNA gyrase activity is either a neutral change or a detrimental change (i.e. a lethal frame shift mutation that takes away the vital gyrase activity).

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.


This message is a reply to:
 Message 225 by herebedragons, posted 12-22-2011 8:12 PM herebedragons has responded

Replies to this message:
 Message 227 by Wounded King, posted 12-23-2011 4:47 AM Taq has responded
 Message 250 by herebedragons, posted 12-27-2011 8:07 AM Taq has not yet responded

  
Wounded King
Member (Idle past 1654 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 227 of 296 (645089)
12-23-2011 4:47 AM
Reply to: Message 226 by Taq
12-23-2011 1:50 AM


This means that any gene that is being actively transcribed is going to see an increase in the mutation rate. This includes vital housekeeping genes.

I cited DNA gyrase as one of those genes, and it serves as a good example. In the experiment, the DNA gyrase gene worked just fine. There was no environmental pressure for the gyrase gene to change. From my own work, I know that any living cell is always actively copying this gene from DNA to RNA. That is why they call it a housekeeping gene. This means that this gene is always incurring more mutations than genes that are not actively being transcribed from DNA to RNA. The only result of mutating this gene in an environment that does not need a change in DNA gyrase activity is either a neutral change or a detrimental change (i.e. a lethal frame shift mutation that takes away the vital gyrase activity).

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.

I don't think this argument really hangs together to counter the 'directed mutation' idea. I agree that substantially the same mechanism, the non transcribed strand in the single stranded DNA state during transcription's increased susceptibility to mutation, does make constitutively transcribed housekeeping genes more susceptible to mutation in general. 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. So the housekeeping genes wont see any increase in their normal mutation rate, which we already agree is likely to be above the basal rate for the genome.

Do you have any reason to think that gyrase is substantially upregulated above its constitutive levels by leucine starvation?

It is an increase in changes that are random with respect to fitness.

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. Wright acknowledges that this will include beneficial, neutral and deleterious mutations but suggests that such a targeted increase will nevertheless improve the chances of the population producing beneficial mutations in that region above the constitutive rate of beneficial mutations in that region, while not affecting the mutation rate at other loci.

TTFN,

WK

Edited by Wounded King, : No reason given.


This message is a reply to:
 Message 226 by Taq, posted 12-23-2011 1:50 AM Taq has responded

Replies to this message:
 Message 235 by Taq, posted 12-23-2011 1:32 PM Wounded King has responded

    
zi ko
Member (Idle past 1179 days)
Posts: 578
Joined: 01-18-2011


Message 228 of 296 (645112)
12-23-2011 10:53 AM
Reply to: Message 179 by Taq
10-14-2011 11:46 AM


Re: beneficial mutations
So the intelligence is only in effect if the mutation is beneficial?

Then I can prove to you that I have ESP. It is quite simple, really. Just give me a billion dollars and I will buy a billion lottery tickets, using my ESP to choose each number on each ticket. You can just ignore all of the tickets that don't win. The proof that my ESP is accurate is the handful of tickets that do win.

Would you be convinced by this display of my ESP powers?


Nature's intelligence springs out of universal laws. You can't just wipe off universal laws becouse they let detrimental mutations to happen as they can afford it.

--------------------------------------------------------------------------------


This message is a reply to:
 Message 179 by Taq, posted 10-14-2011 11:46 AM Taq has not yet responded

Replies to this message:
 Message 229 by Dr Adequate, posted 12-23-2011 11:09 AM zi ko has responded

    
Dr Adequate
Member
Posts: 15960
Joined: 07-20-2006
Member Rating: 5.6


Message 229 of 296 (645115)
12-23-2011 11:09 AM
Reply to: Message 228 by zi ko
12-23-2011 10:53 AM


Re: beneficial mutations
Nature's intelligence springs out of universal laws. You can't just wipe off universal laws becouse they let detrimental mutations to happen as they can afford it.

And you can't just wipe off the universal law that I always win at roulette just because in fact in the long run I lose. It's still a law, even though it isn't actually true.


This message is a reply to:
 Message 228 by zi ko, posted 12-23-2011 10:53 AM zi ko has responded

Replies to this message:
 Message 232 by zi ko, posted 12-23-2011 12:07 PM Dr Adequate has not yet responded

  
zi ko
Member (Idle past 1179 days)
Posts: 578
Joined: 01-18-2011


Message 230 of 296 (645116)
12-23-2011 11:15 AM
Reply to: Message 188 by Taq
10-17-2011 12:18 PM


Re: beneficial mutations
2. You have not acknowledged the mistakes that I have pointed out. You keep saying that evolution is random. It isn't. Trying to change the subject does not make this mistake go away.

I never said evolution is random. I know that natural selection is not random.What i am saying is : 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. Natural selection being just only a filtering mechanism , does not change the nature of the product.

--------------------------------------------------------------------------------


This message is a reply to:
 Message 188 by Taq, posted 10-17-2011 12:18 PM Taq has responded

Replies to this message:
 Message 234 by Taq, posted 12-23-2011 1:27 PM zi ko has not yet responded
 Message 237 by Percy, posted 12-24-2011 6:16 AM zi ko has not yet responded

    
zi ko
Member (Idle past 1179 days)
Posts: 578
Joined: 01-18-2011


Message 231 of 296 (645119)
12-23-2011 11:59 AM
Reply to: Message 224 by herebedragons
12-22-2011 7:58 PM


Re: Are there RANDOM MUTATIONS?
mutations are “random” with respect to fitness. They occur spontaneously without respect to whether the organism needs it or not. Of course, organisms have mechanisms that help them deal with their environment, such as the one discussed in this paper – hypermutation of a specific region. There is no known mechanism that allows the bacteria to specify the specific mutation that happens but it does allow them to “try” many different mutations and the end result is the population gets “just the right mutation” they need to survive.

Yes mutations are random to fitness but not random to life's preservation. At the bacteria level they more or less are random, but not at metazoa with neural system, which provides the mechanism to let organisms to know what is about "the right mutation" for them.
I don’t know of any situation that would not be considered a mistake).

I could relate the situation when there is neural system.
why do only 2 out of 1 billion get the proper mutation?

Maybe becouse they are enough for life to continue to exist.Mutations here are really random to fitness; nature (universal laws) can allow randomness to play a role and this is done quite often.

Edited by zi ko, : No reason given.


This message is a reply to:
 Message 224 by herebedragons, posted 12-22-2011 7:58 PM herebedragons has not yet responded

Replies to this message:
 Message 233 by Taq, posted 12-23-2011 1:26 PM zi ko has responded

    
zi ko
Member (Idle past 1179 days)
Posts: 578
Joined: 01-18-2011


Message 232 of 296 (645121)
12-23-2011 12:07 PM
Reply to: Message 229 by Dr Adequate
12-23-2011 11:09 AM


Re: beneficial mutations
And you can't just wipe off the universal law that I always win at roulette just because in fact in the long run I lose. It's still a law, even though it isn't actually true.

It is a very weak analogy.

--------------------------------------------------------------------------------


This message is a reply to:
 Message 229 by Dr Adequate, posted 12-23-2011 11:09 AM Dr Adequate has not yet responded

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


Message 233 of 296 (645125)
12-23-2011 1:26 PM
Reply to: Message 231 by zi ko
12-23-2011 11:59 AM


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

Those are the same thing.

At the bacteria level they more or less are random, but not at metazoa with neural system, which provides the mechanism to let organisms to know what is about "the right mutation" for them.

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

Maybe becouse they are enough for life to continue to exist.Mutations here are really random to fitness; nature (universal laws) can allow randomness to play a role and this is done quite often.

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


This message is a reply to:
 Message 231 by zi ko, posted 12-23-2011 11:59 AM zi ko has responded

Replies to this message:
 Message 242 by zi ko, posted 12-24-2011 9:54 AM Taq has responded

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


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.


This message is a reply to:
 Message 230 by zi ko, posted 12-23-2011 11:15 AM zi ko has not yet responded

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


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.


This message is a reply to:
 Message 227 by Wounded King, posted 12-23-2011 4:47 AM Wounded King has responded

Replies to this message:
 Message 236 by Wounded King, posted 12-23-2011 3:40 PM Taq has responded

  
Wounded King
Member (Idle past 1654 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 236 of 296 (645137)
12-23-2011 3:40 PM
Reply to: Message 235 by Taq
12-23-2011 1:32 PM


All upregulated genes are being targeted by this mechanism.

Ok, so what genes are upregulated in response to leucine starvation? Are you claiming that all housekeeping genes are? I'm just trying to get hold of a dataset from a microarray study on isoleucine starvation, not ideal since it is the wrong amino acid but at least we can see most of the genes that are part of the stringent and general starvation responses. There is another one where serine hydroxymate is used to trigger the stringent response, a quick scan of that paper suggests there are about 300 genes significantly upregulated, which is certainly a pretty big chunk of the 4000 or so genes in the E. coli K12 genome.

You seem to be redefining 'upregulated' to mean simply expressed. Upregulation denotes a change in the expression level. A highly expressed housekeeping gene is not upregulated if it simply continues to be highly expressed at the same level.

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.

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.

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.

TTFN,

WK


This message is a reply to:
 Message 235 by Taq, posted 12-23-2011 1:32 PM Taq has responded

Replies to this message:
 Message 251 by herebedragons, posted 12-27-2011 8:18 AM Wounded King has responded
 Message 257 by Taq, posted 01-03-2012 6:20 PM Wounded King has responded

    
Percy
Member
Posts: 16035
From: New Hampshire
Joined: 12-23-2000
Member Rating: 3.0


Message 237 of 296 (645189)
12-24-2011 6:16 AM
Reply to: Message 230 by zi ko
12-23-2011 11:15 AM


Re: beneficial mutations
zi ko writes:

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.

There's a kernel of truth in this. While no evolutionist here believes the products of evolution are random with respect to adaptation, we do believe the specific implementations and methods of adaptation selected by evolution are not predictable. As Stephen Jay Gould said many times (or maybe just was quoted many times), if you rewound the history of life and played it over again, history would not repeat itself. It would be like rewinding a movie to hear a line you missed only to find the line had changed.

Neutral mutations may explain why this is so. Unaffected by selection pressures, neutral mutations are free to go in any direction. If, for instance, the particular whorls of ears and fingerprints are independent of selection then their evolutionary change could go in any direction, in other words, random.

But that life is adapted to its environment cannot be the result of randomness. The specific alternative paths toward adaptation are random, but that life adapts is not due to randomness. Think of it like a gumdrop factory that produces gumdrops of all colors, but a machine on the end selects only red. No one would call the process by which only red gumdrops emerge from the factory random. Or consider a backgammon game. The rolls of the dice are random, but the decisions about what to do are based upon the board position, analogous to the environment. Allplayers get random rolls, but the better players are able to, ahem, better adapt those rolls to the current situation.

--Percy

Edited by Percy, : Fix 2nd sentence of last paragraph.


This message is a reply to:
 Message 230 by zi ko, posted 12-23-2011 11:15 AM zi ko has not yet responded

Replies to this message:
 Message 238 by Chuck77, posted 12-24-2011 6:24 AM Percy has responded

    
Chuck77
Inactive Member


Message 238 of 296 (645190)
12-24-2011 6:24 AM
Reply to: Message 237 by Percy
12-24-2011 6:16 AM


Re: beneficial mutations
Percy writes:

Think of it like a gumdrop factory that produces gumdrops of all colors, but a machine on the end selects only red. No one would call the process by which only red gumdrops emerge from the factory random.

I don't agree with what zi ko believes as far as evolution but if I we're advocating for him I would say if there was no factory it would be random no doubt. So let's just call the "factory" the designer, therefore, not random.


This message is a reply to:
 Message 237 by Percy, posted 12-24-2011 6:16 AM Percy has responded

Replies to this message:
 Message 239 by Percy, posted 12-24-2011 6:29 AM Chuck77 has responded

  
Percy
Member
Posts: 16035
From: New Hampshire
Joined: 12-23-2000
Member Rating: 3.0


Message 239 of 296 (645191)
12-24-2011 6:29 AM
Reply to: Message 238 by Chuck77
12-24-2011 6:24 AM


Re: beneficial mutations
Chuck77 writes:

I don't agree with what zi ko believes as far as evolution but if I we're advocating for him I would say if there was no factory it would be random no doubt. So let's just call the "factory" the designer, therefore, not random.

I'd be guessing as to what you're trying to say, so I won't attempt response.

--Percy


This message is a reply to:
 Message 238 by Chuck77, posted 12-24-2011 6:24 AM Chuck77 has responded

Replies to this message:
 Message 240 by Chuck77, posted 12-24-2011 6:34 AM Percy has responded

    
Chuck77
Inactive Member


Message 240 of 296 (645192)
12-24-2011 6:34 AM
Reply to: Message 239 by Percy
12-24-2011 6:29 AM


Re: beneficial mutations
I think zi ko believes there is a designer involved. You used a factory as an example of why things arent random. I just mean things aren't random because of a desinger (your factory).

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

Edited by Chuck77, : No reason given.

Edited by Chuck77, : No reason given.


This message is a reply to:
 Message 239 by Percy, posted 12-24-2011 6:29 AM Percy has responded

Replies to this message:
 Message 241 by Percy, posted 12-24-2011 8:59 AM Chuck77 has acknowledged this reply
 Message 243 by zi ko, posted 12-24-2011 10:20 AM Chuck77 has not yet responded

  
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