Random mutations

As I understand it random mutations are random WRT to their effect on the fitness of the organism.
Is this the best way to describe it?
If so what evidence is used to support this idea?
What might falsify it?

[This message has been edited by judge, 11-25-2003]

[This message has been edited by judge, 11-25-2003]

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As I understand it random mutations are random WRT to their effect on the fitness of the organism.

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Random mutations occur in the DNA, for instance a cytosine is changed to a tyrosine. The effects of each mutation can be deleterious (bad), neutral (no change), and beneficial (good). How we determine the advantage or disadvantage of each mutation is somewhat ad hoc, but the overall agreement is that if a mutation allows an organism to reproduce at a higher rate or fill a new niche it is advantageous.

So, saying that the effect on fitness is random isn't quite accurate, rather mutations are random changes in the DNA which may or may not affect fitness. Although there are "mutational hotspots", or areas in the genome that have a slightly higher rate of mutation, whether or not the actual mutation happens is still random among individuals.

I can look up some papers for you if you wish, but suffice it to say that studies that have looked at antibiotic resistance in bacteria, for example, have not seen the same mutation occuring among all resistant bacteria. It doesn't look like there is a mechanism that allows organisms to specifically change their DNA in response to an environmental stress. Rather, mutants are selected for by the environment.

One possible way to falsify this would be to look at different mutants that have arisen in different locals and see if they are exhibiting the same exact mutation and no other mutation. It is possible that only one possible mutation is going to work and is being selected for, but this is highly unlikely. Another falsification would be the discovery of a mutational enzyme that is responsible for all mutations in the genome. This mutational enzyme would be "front-loaded", in other words the enzyme creates specific mutations to specific stimuli. So far, enzymes of this nature have not been observed (to my knowledge) and random mistakes in DNA duplication seem to be the rule.

WRT?

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"Illuminant light,
illuminate me."

wrt=with respect to

Loudmouth:
So, saying that the effect on fitness is random isn't quite accurate, rather mutations are random changes in the DNA which may or may not affect fitness.

Judge:
So does it mean random as in "unpredictable".
Is it that the "mutagen" (is that right) is not disposed in any particular way WRT fitness?

Loudmouth:

I can look up some papers for you if you wish, but suffice it to say that studies that have looked at antibiotic resistance in bacteria, for example, have not seen the same mutation occuring among all resistant bacteria. It doesn't look like there is a mechanism that allows organisms to specifically change their DNA in response to an environmental stress. Rather, mutants are selected for by the environment.

Judge:
That would be great if you have the time. I am trying to learn more about the science of this and how science actually works.

[This message has been edited by judge, 11-25-2003]

Loudmouth writes:

quote:

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One possible way to falsify this would be to look at different mutants that have arisen in different locals and see if they are exhibiting the same exact mutation and no other mutation. It is possible that only one possible mutation is going to work and is being selected for, but this is highly unlikely.

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It has, however, been seen:

Hall BG.
On the specificity of adaptive mutations.
Genetics. 1997 Jan;145(1):39-44.
PMID: 9017388 [PubMed - indexed for MEDLINE]

From the abstract:

Here I use the ebg system to provide evidence that when selection is applied to one specific nucleotide site within a gene, mutation occurs at that site but not at an alternative and equally mutable site within the same gene.

It seems that selective pressures can be specific enough to result in only those organisms that acquire specific mutations.

Hall seems to specialize in adaptive mutations. Some more interesting results:

Hall BG.

Adaptive mutagenesis: a process that generates almost exclusively beneficial mutations.
Genetica. 1998;102-103(1-6):109-25. Review.
PMID: 9720275 [PubMed - indexed for MEDLINE]

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Rrhain
WWJD? JWRTFM!

quote:

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It seems that selective pressures can be specific enough to result in only those organisms that acquire specific mutations.

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Yes, I should have made that a little more specific. Mutations are random in themselves but selection weeds out some before they can be observed.

I was trying to find a paper on the frequency of random mutations and found this paper and abstract

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Single sperm analysis of the trinucleotide repeats in the Huntington's disease gene: quantification of the mutation frequency spectrum
Esther P.Leeflang, Lin Zhang, Simon Tavaré, Rene Hubert, Jayalakshmi Srinidhi, Marcy E.MacDonald, Richard H.Myers, Margot de Young, Nancy S.Wexler, James F.Gusella and Norman Arnheim*

*To whom correspondence should be addressed
Received April 10,1995; Revised and Accepted June 2,1995

Thee CAG triplet repeat region of the Huntington's disease gene was amplified in 923 single sperm from three affected and two normal individuals. Average-size alleles (15-18 repeats) showed only three contraction mutations among 475 sperm (0.6%). A 30 repeat normal allele showed an 11% mutation frequency. The mutation frequency of a 36 repeat intermediate allele was 53% with 8% of all gametes having expansions which brought the allele size into the HD disease range (>=38 repeats). Disease alleles (38-51 repeats) showed a very high mutation frequency (92-99%). As repeat number increased there was a marked elevation in the frequency of expansions, in the mean number of repeats added per expansion and the size of the largest observed expansion. Contraction frequencies also appeared to increase with allele size but decreased as repeat number exceeded 36. Our sperm typing data are of a discrete nature rather than consisting of smears of PCR product from pooled sperm. This allowed the observed mutation frequency spectra to be compared to the distribution calculated using discrete stochastic models based on current molecular ideas of the expansion process. An excellent fit was found when the model specified that a random number of repeats are added during the progression of the polymerase through the repeated region.

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These are PCR's of single sperm which are not put under strict selective pressure and show high levels of additional repeats (a type of mutation). The distribution of repeats among single sperm appeared to be random. This would seem to be a hotspot for repeat polymorphisms, but point mutations could be caused by mutagens in a random sense in non-selected sperm as well.

The entire paper can be found here.

Rrhain:
It seems that selective pressures can be specific enough to result in only those organisms that acquire specific mutations.

Judge:
Does this mean that at one point there were (or may have been) organisms that aquire specific mutations and other organisms (which otherwise were much the same) that did not aquire these same mutations; and that the organisms that aquired the mutations were selected for?
And I suppose that the tendency to aquire these mutations is reatained?

The result being that we now have some organisms that aquire specific mutations and that although these mutations are in fact random they appear non random (so to speak).

Sorry if this is wordy .

[This message has been edited by judge, 11-25-2003]

[This message has been edited by judge, 11-25-2003]

judge,

Basically, from what I can glean from the abstract, it's kinda like playing a game of Yacht where the only way to get into the next round is to roll five 6s on the very first roll.

The die roll is completely random, but the selective pressure is so specific that only a certain type is selected for.

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Rrhain
WWJD? JWRTFM!

Hi judge,
It also explains the basis of molecular phylogenetics (and indicates a problem that can occur). You can find organisms that share a specific mutation and it is assumed to be due to common descent. However, make a bad pick of gene to analyze i.e. one that is heavily constrained, you will tend to see the same mutation appearing in non-related organisms because it either confers a specific benefit not specific to any organism or it is the only part of the gene allowed to mutate without being immediately selected out (note the mutations happen anywhere but outside of a specific sequence it might be lethal). This would tend to make a false association of the organisms sharing the mutation/allele as they do not share the mutation by common descent. Sorry to make things more complicated. Yes the mutations are random but who survives which mutation is not.

I think it is best if we ignore my last post , I misunderstood something you said and went off into another dimension

Rrhain:
judge,

Basically, from what I can glean from the abstract, it's kinda like playing a game of Yacht where the only way to get into the next round is to roll five 6s on the very first roll.

The die roll is completely random, but the selective pressure is so specific that only a certain type is selected for.

Judge:
If there were a realtion between the environment "triggereing" a mutation or even an increased likelihood of a particular mutation it would be difficult to falsify or even find compelling evidence for.

Is this correct?

And so although it may be possible to "find" anomolies the simplest explanation (and the one which appears to be true) is that particular (beneficial)mutations are never "triggered" by environmental influences.

[This message has been edited by judge, 11-26-2003]

judge writes:

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If there were a realtion between the environment "triggereing" a mutation or even an increased likelihood of a particular mutation it would be difficult to falsify or even find compelling evidence for.

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Difficult, yes, but from what I understand of the process, not impossible. One test is to see if there are reversion mutations or to alter an organism and see if it mutates back. There are known to be mutational hot spots.

Also, mutations can only happen with what you have. That is, it may be the pressure is so strong that only those who have a deletion mutation in a certain gene get selected, if you don't have that gene in the first place, that pressure simply may not apply to you. For example, the environment may be such that those who need to eat food for their vitamin C (like, say, humans or guinea pigs or trout) will need to have a certain mutation in order to process the food present in the environment for vitamin C. But if you can synthesize your own vitamin C (like almost all other mammals), you don't really have that pressure being applied to you.

quote:

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And so although it may be possible to "find" anomolies the simplest explanation (and the one which appears to be true) is that particular (beneficial)mutations are never "triggered" by environmental influences.

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Well, never say "never." Since we can see it happening, there's no reason to deny it. We need to research it to find out more of what's going on.

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Rrhain
WWJD? JWRTFM!

Thanks for the replies....I get the WWJD? bit but the next part loses me.

Jesus Would Read The Frickin' Manual.

RTFM is a common tech support acronym used to describe calls that would never have occurred if the user had simply perused the documentation that accompanied the software in the first place.

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Rrhain
WWJD? JWRTFM!

I saw this science daily article, and I was wondering if anyone wanted to speculate on the implications.

http://www.sciencedaily.com/releases/2005/05/050518175350.htm

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This research raises fundamental questions about evolution. Biologists have often thought about evolution in the same way many think about death and taxes -- something inevitable. But Romesberg is a chemist, and he found himself asking not only how, but why evolution happens.
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Are mutations as random as we thought? Maybe mutations are controlled by pre-programming. If so, how could we have evolved the program in the first place?

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This brought Romesberg to the conclusion that mutation is a programmed stress response -- a survival mechanism.
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This message has been edited by Limbo, 05-19-2005 01:24 AM