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  Topic: Random Mutation, an examination< Next Oldest | Next Newest >  
skeptic



Posts: 1163
Joined: May 2006

(Permalink) Posted: July 19 2007,14:09   

Picking up on a conversion Eric Murphy and I had last year, I'd like to get some perspectives on the "randomness" of random mutation.  I'm looking at SNPs and frame shifts and trying to tease out exactly what is meant by random.  This comes up based up the project I'm currently working on and programming "randomness."

Just looking for some opinions, which I know I can count on you guys for.

  
Louis



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(Permalink) Posted: July 19 2007,14:17   

Unless I'm mistaken (and I hope I am), you are making a request for information by using a veiled and calculated insult. "Opinions"?

Good start.

Louis

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Shirley Knott



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(Permalink) Posted: July 19 2007,16:35   

It would be useful/helpful if you could explain what you mean by 'random'.  What do you think is being claimed when it is claimed that mutations are random?
Clearly (?) no one is asserting that mutations are randome with respect to the laws of chemistry or physics.
Equally clearly, no one is successfully maintaining that mutations are 'pre-planned' or 'guided by intelligence'.
What do you think randomness means with respect to mutation?
Why do you find this problematic, or, if you don't find it problematic, what about 'random mutation' do you think needs clarification/explanation?

hugs,
Shirley Knott

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: July 19 2007,17:02   

"Random" means "mutations do not appear when and where they are needed.  They can happen, anywhere, anytime, or never even happen at all."

The creationists, of course, simply blither stupidly about the whole idea, since they don't understand any of it.  (shrug)

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skeptic



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(Permalink) Posted: July 19 2007,17:45   

No insults here just looking for some ideas.  I have a feeling someone will say something or make a comparison that will push me in the right direction.  I'm trying to model this and the vagueness of random is difficult to program.

We know that mutations do not occur equally across the genome so that throws that out.  Eric would always tell me that mutations occurred without regard for the resulting fitness of the organism and thus random.  The problem with that is it's a retrospective analysis and again difficult to program.

I could cop-out and just apply a mutation rate arbitrarily but I'd like a better treatment than that and it wouldn't work for my ultimate goal anyway.

So, my main hang up is I'm looking for something more than semantic that I can use.  I've found in the past that when I'm confronted by a problem the more opinions I can collect the better likelihood that someone else will say something or use a particular analogy that either inspires me or clarifies the problem.  Just wanting to pick you guys brains for my own gains.  Sorry if that sounds selfish.

  
swbarnes2



Posts: 78
Joined: Mar. 2006

(Permalink) Posted: July 19 2007,19:41   

Quote (skeptic @ July 19 2007,17:45)
No insults here just looking for some ideas.  I have a feeling someone will say something or make a comparison that will push me in the right direction.  I'm trying to model this and the vagueness of random is difficult to program.

We know that mutations do not occur equally across the genome so that throws that out.  Eric would always tell me that mutations occurred without regard for the resulting fitness of the organism and thus random.  The problem with that is it's a retrospective analysis and again difficult to program.

I could cop-out and just apply a mutation rate arbitrarily but I'd like a better treatment than that and it wouldn't work for my ultimate goal anyway.

So, my main hang up is I'm looking for something more than semantic that I can use.  I've found in the past that when I'm confronted by a problem the more opinions I can collect the better likelihood that someone else will say something or use a particular analogy that either inspires me or clarifies the problem.  Just wanting to pick you guys brains for my own gains.  Sorry if that sounds selfish.

Okay, so you started by querying NCBI for their SNPs and indels, right?

So what exactly do you hope to learn from people on a board that you can't learn from looking at the primary data?  Surely you looked at the available empirical data before you decided to start a fight over what "random" mean, right?  Surely you'd prefer to draw your conclusions based on the data, and not by analogy, right?  Far less "semantic" that way.

What kind of answer are you expecting anyway?  Someone to give you a list of every single 10-mer, with all the probabilities of every kind of mutation in every position for each?

Or the whole human genome (or mouse, or fly, or whatever), with every base pair annotated with the odds of every kind of mutation happening there?

If you want, for instance, the percentages of mutations found in ENU-generated mutants, those papers exist.  Surely you aren't asking for those.

  
skeptic



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(Permalink) Posted: July 19 2007,21:11   

Nothing like that.  I want to represent mutations within a computer simulation so I need a generalized rule or set of rules to do so.  Raw data is not exactly, although somewhat, helpful in this regard.  I hope you see what I'm getting at.

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: July 19 2007,21:14   

Quote (skeptic @ July 19 2007,21:11)
 I want to represent mutations within a computer simulation so I need a generalized rule or set of rules to do so.  

There aren't any.

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Henry J



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(Permalink) Posted: July 19 2007,22:52   

Example of random: In a species with 4 billion base pairs in each cell, and a population of a several billion, the next several billion mutations will be widely scattered over most of those 4 billion base pairs.

Of course, sections critical to functionality would have fewer persistent mutations. (Not that they wouldn't happen, but that they wouldn't persist in the gene pool.)

The result is that genetic variety will increase until other processes remove it as fast as it gets added. (Or decrease if it's already above that point.)

imo, there's often too much attention given to single mutations. That's sort of like focusing on one raindrop when its raining.

Henry

  
BWE



Posts: 1898
Joined: Jan. 2006

(Permalink) Posted: July 19 2007,23:40   

Skeptic, It sounds to me like you are trying to model fitness after mutations. There is a kind of obvious problem there. Is that it? What would you model otherwise?

Somewhere, I just googled and didn't find it, there's a guy who takes the raw data from known genomes and does a cool visual display of random mutations until it hits a different species' sequence. But it isn't science, it's art. There were all kinds of caveats.

Maybe that helps. Anybody know what I'm talking about? You see this speckly tube on a plasma screen that twists and turns and eventually stops and a picture of the new organism comes on? I thought I saw it on Nova as a cool art installation that went with some traveling exhibit but I don't recall and can't find it.

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When wished on the morning star
Somebody thought of that, and someone believed it
Look what it's done so far

The Daily Wingnut

   
Louis



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(Permalink) Posted: July 20 2007,03:27   

Quote (skeptic @ July 19 2007,23:45)
No insults here just looking for some ideas.

Then like I said, I'm happy to be wrong.

Louis

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Bye.

  
JonF



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(Permalink) Posted: July 20 2007,07:58   

Quote (skeptic @ July 19 2007,18:45)
Eric would always tell me that mutations occurred without regard for the resulting fitness of the organism and thus random.  The problem with that is it's a retrospective analysis and again difficult to program.

Luria-Delbrück experiment.

  
Albatrossity2



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Joined: Mar. 2007

(Permalink) Posted: July 20 2007,08:28   

Quote (JonF @ July 20 2007,07:58)

Luria-Delbrück experiment.

The Luria-Delbruck Fluctation test has also been used with cultured mouse cells (GENETIC ANALYSIS OF AZAGUANINE RESISTANCE IN AN ESTABLISHED MOUSE CELL LINE, MORROW J., GENETICS 65 (2): 279-& 1970). Send me a PM if you want a PDF version of this paper.

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As the only possible proof of its own inheritance.
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qetzal



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(Permalink) Posted: July 20 2007,22:59   

Quote (skeptic @ July 19 2007,21:11)
Nothing like that.  I want to represent mutations within a computer simulation so I need a generalized rule or set of rules to do so.  Raw data is not exactly, although somewhat, helpful in this regard.  I hope you see what I'm getting at.

I think your question is too general. There are too many kinds of mutations, and their frequencies are dependent on circumstance and context.

In some cases, you can specify simple rules. E.g. for base substitutions, transitions usually outnumber transversions. I don't recall the relative percentages off-hand, and again it would depend on the circumstances, but you could find such numbers if you wanted.

But if you want a general set of rules for modeling substitutions and small deletions/insertions and large deletions/insertions and inversions and duplications and translocations and transpositions and etc., I think you're out of luck.

One other thing to keep in mind. We can only derive rules on mutations by sequencing, and we can only sequence mutations that are recoverable. There's no guarantee that recoverable mutations are representative of which mutations actually occur.

  
skeptic



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(Permalink) Posted: July 21 2007,00:15   

I agree, I'm going to have to go with some basic assumptions but it gave me another idea.  I might actually use competing sets and compare outcomes but that might just be for curiosity's sake.  My final goal is to develop a minimal gene organism model and use it for simulations to test toxins, environmental changes, population dynamics and so on.  The organism would be hypothetical so I'd want to generalize specific data as much as possible and that may not be too easy.

Thanks for the reference, Alba, that also supplies me with a bunch of citations to follow-up.

  
qetzal



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Joined: Feb. 2006

(Permalink) Posted: July 21 2007,00:58   

Quote (skeptic @ July 21 2007,00:15)
My final goal is to develop a minimal gene organism model and use it for simulations to test toxins, environmental changes, population dynamics and so on.  The organism would be hypothetical so I'd want to generalize specific data as much as possible and that may not be too easy.

Sounds pretty ambitious. I doubt the requisite knowledge exists to accurately model such things, but I wish you luck with it.

  
skeptic



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(Permalink) Posted: July 21 2007,01:36   

yeah, kinda like the whole cell model, it's a bit of a holy grail but I'm taking at stab at it.

  
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