recurrent mutation

Discussion in 'Human Science' started by Robert_js, Oct 24, 2004.

  1. Robert_js Registered Senior Member

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    I was reading the article “Introduction to Evolutionary Biology” Version 2 by Chris Colby (on the talkorigins website) and came across the following sections -:

    Except in rare cases of high gene flow, new alleles enter the gene pool as a single copy. Most new alleles added to the gene pool are lost almost immediately due to drift or selection; only a small percent ever reach a high frequency in the population. Even most moderately beneficial alleles are lost due to drift when they appear. But, a mutation can reappear numerous times. …

    J. B. S. Haldane developed many of the mathematical models of natural and artificial selection. He showed that selection and mutation could oppose each other, that deleterious mutations could remain in a population due to recurrent mutation.​

    Does this mean that a section of DNA will mutate in a certain way. But if that mutated section of DNA is not taken up in the species offspring then it is likely that more sections of DNA will be mutated in exactly the same way giving the new genetic sequence a better chance of passing into the next generation?
     
  2. Hercules Rockefeller voltage gated ion channel Moderator

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    <P>
    No and no.<P>
     
  3. Robert_js Registered Senior Member

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    Then what is meant by “recurrent mutation” and what does Chris Colby mean when he says; “a mutation can reappear many times”?
     
  4. Hercules Rockefeller voltage gated ion channel Moderator

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    In this sentence......

    ......I take the phrase “recurrent mutation” to simply mean that organisms are constantly acquiring mutations. Whether mutations are lost or maintained is another matter. But because of the constant gain and loss of mutations, different (or maybe even the same) “deleterious mutations could remain in a population”.

    One thing that may be confusing is this statement......

    I do not think that this phrase is referring to the <I><B>exact same mutation</B></I> occurring independently. In other words, it’s not referring to a situation where nucleotide 719 is mutated from A->T on two separate occasions. I think it’s referring mutations producing new <I><B>alleles</B></I> of a given gene. There are lots of different types of mutations that can occur in various exon positions of a gene. Nucleotide changes may result in amino acid changes in the protein. Amino acid changes will either result in a protein with unaltered function, a protein with an altered function (most likely a reduced function) or a protein with no function (a null mutation). (I am not even going to touch on intron mutations or regulatory mutations that affect other aspects if protein functions such as splicing, processing or regulation.) So hopefully you can see that different mutations in different parts of a gene can end up creating two different proteins that both have, for example, a 50% reduction in function. IOW, two different alleles of the same gene have been created. For instance, there are many human genetic diseases for which there are multiple alleles. (ie. different mutations in different parts of the gene that produce the same phenotype/disease).
     
  5. Robert_js Registered Senior Member

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    I do not think the above is merely referring to “constantly acquiring mutations”. “Recurrent mutation” refers to the same mutation reappearing many times.

    Chris Colby again in his article “Introduction to Evolutionary Biology” from Talking Origins.

    Beneficial alleles

    Most new mutants are lost, even beneficial ones. Wright calculated that the probability of fixation of a beneficial allele is 2s. (This assumes a large population size, a small fitness benefit, and that heterozygotes have an intermediate fitness. A benefit of 2s yields an overall rate of evolution: k=4Nvs where v is the mutation rate to beneficial alleles) An allele that conferred a one percent increase in fitness only has a two percent chance of fixing. The probability of fixation of beneficial type of mutant is boosted by recurrent mutation. The beneficial mutant may be lost several times, but eventually it will arise and stick in a population. (Recall that even deleterious mutants recur in a population.) ​

    The above is clearly referring to the same mutation reappearing many times.

    The phrase “recurrent mutation” or “mutations that reappear many times” would seem to me to be referring to the exact same mutation reappearing many times.

    From the Journal of Medical Genetics 2003;40:e82 © 2003 BMJ Publishing Group

    http://jmg.bmjjournals.com/cgi/content/full/40/6/e82

    Recurrent mutations in the NF1 gene are common among neurofibromatosis type 1 patients

    Key points

    The neurofibromatosis type 1 gene (NF1) has been described as bearing one of the highest mutation rates in the human genome. Half of the patients affected by NF1 are sporadic cases of the disease. Up to now it has been thought that most of these patients have private mutations which, in addition to the large size of the gene, has greatly hampered the definition of the mutational spectrum in NF1 patients.

    We present here our experience of four years using the cDNA-SSCP/HD approach for mutational screening of the whole NF1 coding region. We have searched for NF1 mutations in 474 unrelated subjects suspected of having NF1. We have identified 142 different NF1 mutations in 189 patients. One hundred and four of these mutations have been found only once in this study, while the remaining 38 mutations have either been detected more than once in this study or have previously been published. Thus, we observed that 85 of 189 patients for which we identified a NF1 mutation (45%) harbour a recurrent mutation.

    All detected alterations were characterised both at the genomic and RNA level. Considering the mutation effect in RNA processing, we have observed that 50% of patients harbour mutations that would lead to a recurrent alteration in mRNA. The detection of this high number of recurrent mutations could modify the routine genetic testing of the NF1 gene by performing a search for these recurrent mutations as a first analytical step
    .​
    So how does the same mutation reappear many times? The statistical probability of the same mutation reappearing more than once is minute. The probability of it reoccurring many times is zero.
     
  6. Raithere plagued by infinities Valued Senior Member

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    The rate of mutation is not constant across the entire genome. Some genes and gene segments have much higher rates of mutation than others. Those segments with higher rates are more likely to have recurrent mutations within a population. You cannot simply apply the average rate of mutation across the genome to give the probability of any single mutation, it varies. Thus certain mutations will be more common than average.

    ~Raithere
     
  7. Robert_js Registered Senior Member

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    Yes; these sections are called hot spots.

    I do not understand this. Are these “certain mutations” the exact same changes to the DNA sequence? Does the same so called random mistakes in the DNA sequence keep popping up time and time again?

    Just because a section of DNA has a higher mutation rate it does not follow that the same mutation will reoccur. Surely a mutation can only be a mistake or a random disordering of the genetic code. If so then it is highly improbable that the same mutation will reoccur.
     
  8. Raithere plagued by infinities Valued Senior Member

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    It's simply not improbable, Robert. It really doesn't matter what anyone thinks the probability should be. What matters is what we observe.

    "Example: achondroplasia occurs sporadically (in families with no previous history) as a result of new mutations in the gene for the fibroblast growth factor receptor. One study detected seven infants born with sporadic achondroplasia in one year among 242,257 total births recorded." - http://www-personal.ksu.edu/~bethmont/mutdes.html

    Thus the rate of this particular mutation is observed to be 1 in 34,608 individuals which isn't very high. You can argue all day based upon whatever numbers you like that identical mutations should be exceedingly rare, the fact is they aren't.

    ~Raithere

    P.S. Sorry, I forgot to answer your other question. I believe that, as in the example I gave, most of the time we are talking about any mutation within that gene that causes it to malfunction so we're not necessarily dealing with an identical mutation. Still these will occur, just not as often. If I find something specific I'll post it for you.
     
    Last edited: Nov 4, 2004
  9. Robert_js Registered Senior Member

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    I am not arguing what the rate of a mutation is. You only have to look on the internet for a given mutation and you can easily find out what the estimated mutation rate is.

    But if you were playing cards with someone who kept on being dealt a full house would you merely say; “It really doesn't matter what anyone thinks the probability should be. What matters is what we observe.” And what if the person who was getting all these full houses said; “You can argue all day based upon whatever numbers you like that a (full house) should be exceedingly rare, the fact is they aren't.” Would you be happy with this answer? Or would you be suspicious that something was going on that is not obvious to the observer.

    As with recurrent mutations I am a little suspicious that something is happening that is not obvious to the casual observer. Also with hot spots that mutate specific sections of DNA. And with the immune system that mutates sections of DNA at 1,000,000 times the background mutation rate and then rearranges it to fight off antigens that have never existed on earth before.
     
  10. Raithere plagued by infinities Valued Senior Member

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    Robert:

    That you're suspicious is good. That you invent invisible forces to explain away the problem is not.

    If someone kept getting dealt full houses would you assume that God was performing miracles on the deck or would you suspect that the dealer was not dealing cards out at random? How would you go about determining the answer?

    As with hot spots and recurrent mutations the more reasonable choice is that mutation is not completely random, at least not across the entire genome. And as we continue to investigate the matter we are finding that this is indeed the case.

    At the very least you should investigate the natural explanation before declaring it irresolvable or impossible and jumping of into tales of the supernatural that you cannot test for or even explain.

    ~Raithere
     
  11. Robert_js Registered Senior Member

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    I would assume someone was cheating and leave the game. So when I see unexplained probability (whether in a card game or in some scientific explanation of natural phenomenon) I opt out.
     
  12. Roman Banned

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    There is no such thing as a beneficial mutation. Your science is flawed and bogus. When will you see that evolution is wrong and accept the truth?

    All praise the ancient of days.
     
  13. hotsexyangelprincess WMD Registered Senior Member

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    what do you mean no such thing as a beneficial mutation? of course there is :m:
     
  14. Roman Banned

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    Shit, I was just playing.
     
  15. Raithere plagued by infinities Valued Senior Member

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    Robert, you wouldn't make a good scientist.

    ~Raithere
     
  16. hotsexyangelprincess WMD Registered Senior Member

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    ok roman. i thought you were serious. that terrified me. :m:
     
  17. Robert_js Registered Senior Member

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    Raithere

    Galileo; “My calculations show that the earth revolves around the sun.”

    Pope; “It really doesn’t matter what your calculations are. What matters is what we observe.

    Galileo; “But based on my observations it is impossible that the earth is at the centre of the universe.”

    Pope; “If the earth is round then how come people at the bottom do not fall off. You can argue all day that your calculations and observations show the earth revolves around the sun, the fact is it doesn’t.

    Galileo; “There is no such thing as top and bottom. There is a force that rotates the earth around the sun every 365 days. This is some kind of magnetic force that holds everthing to the earth whether it is north or south.”

    Pope;That you invent invisible forces to explain away the problem is not good. You would not make a good scientist.
     
    Last edited: Nov 13, 2004

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