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Thread: Evidence of non-random mutation rates suggests an evolutionary risk mangemnt strategy

  1. #1

    Default Evidence of non-random mutation rates suggests an evolutionary risk mangemnt strategy

    Evidence of non-random mutation rates suggests an evolutionary risk management strategy

    A central tenet in evolutionary theory is that mutations occur randomly with respect to their value to an organism; selection then governs whether they are fixed in a population. This principle has been challenged by long-standing theoretical models predicting that selection could modulate the rate of mutation itself1, 2. However, our understanding of how the mutation rate varies between different sites within a genome has been hindered by technical difficulties in measuring it. Here we present a study that overcomes previous limitations by combining phylogenetic and population genetic techniques. Upon comparing 34 Escherichia coli genomes, we observe that the neutral mutation rate varies by more than an order of magnitude across 2,659 genes, with mutational hot and cold spots spanning several kilobases. Importantly, the variation is not random: we detect a lower rate in highly expressed genes and in those undergoing stronger purifying selection. Our observations suggest that the mutation rate has been evolutionarily optimized to reduce the risk of deleterious mutations. Current knowledge of factors influencing the mutation rate—including transcription-coupled repair and context-dependent mutagenesis—do not explain these observations, indicating that additional mechanisms must be involved. The findings have important implications for our understanding of evolution and the control of mutations.
    Bacteria Evolved Way to Safeguard Crucial Genetic Material
    ScienceDaily (Apr. 23, 2012) — Just as banks store away only the most valuable possessions in the most secure safes, cells prioritise which genes they guard most closely, researchers at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) have found. The study, just published online in Nature, shows that bacteria have evolved a mechanism that protects important genes from random mutation, effectively reducing the risk of self-destruction. The findings answer a question that has been under debate for half a century and provide insights into how disease-causing mutations arise and pathogens evolve.

    Different genes mutate at different rates, in the bacterium E. coli. (Credit: EMBL / I. Martincorena

    "We discovered that there must be a molecular mechanism that preferentially protects certain areas of the genome over others," says Nicholas Luscombe, who led the research at EMBL-EBI. "If we can identify the proteins involved and uncover how this works, we will be even closer to understanding how mutations that lead to diseases like cancer can be prevented."
    Mutations are the reason each of us is unique. These changes to our genetic material are at the root of variation between individuals, and between cells within individuals. But they also have a darker side. If it affects an important gene -- for example, rendering a tumour-suppressing gene useless -- a mutation can have disastrous consequences. Nevertheless, protecting all genes from mutation would use up too many of the cell's resources, just like holding all deposits in maximum-security safes would be prohibitively expensive. Iñigo Martincorena, a PhD student in Luscombe's lab, has now found that cells evolved a 'risk management' strategy to address this issue.
    Looking at 120,000 tiny genetic mutations called single nucleotide polymorphisms (SNPs) in 34 strains of the bacterium E. coli, the scientists were able to quantify how random the mutation rate was in different areas of the bacterial genomes. Their results showed that key genes mutate at a much lower rate than the rest of the genetic material, which decreases the risk of such genes suffering a detrimental mutation. "We were struck by how variable the mutation rate appears to be along the genome," says Martincorena. "Our observations suggest these bacteria have evolved a clever mechanism to control the rate of evolution in crucial areas of the genome."
    Using population genetics techniques, the researchers were able to disentangle the effects of mutation rate and natural selection on mutations, settling a long-standing debate in the field. Scientists have long thought that the chances of a mutation occurring were independent of its value to an organism. Once the mutation had occurred, it would undergo natural selection, spreading through the population or being eliminated depending on how beneficial or detrimental the genetic change proved to be.
    "For many years in evolution there has been an assumption that mutations occur randomly, and that selection 'cleans them up'," explains Martincorena. "But what we see here suggests that genomes have developed mechanisms to avoid mutations in regions that are more valuable than others."
    Observations from studies of cancer genomes suggest that similar mechanisms may be involved in the development of cancers, so Luscombe and colleagues would now like to investigate exactly how this risk-managing gene protection works at a molecular level, and what role it may play in tumour cells.
    Thought this was interesting.
    You can't trust a meta-ethical moral relativist since such a person can abuse reason to justify any act.


  2. #2
    Super Grandmaster evilstebunny's Avatar
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    "But what we see here suggests that genomes have developed mechanisms to avoid mutations in regions that are more valuable than others."
    Could this be evidence of intelligent design?

  3. #3

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    Quote Originally Posted by evilstebunny View Post
    Could this be evidence of intelligent design?
    I personally think that it could be evidence that the function of evolution is more complicated than we realise. Intelligent design based on this is a long shot, but can't be ruled out. ( But not on the standard intelligent design model, according to that, organisms will never change and have never changed )
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  4. #4

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    Quote Originally Posted by evilstebunny View Post
    Could this be evidence of intelligent design?
    I don't think so. It just demonstrates again that mutations are not random.

    The random part in random variation is not really random when it comes to mutations. Professor Dan Graur writes in his article “Single-base Mutation” in Encyclopedia of Life Sciences that mutations do not occur randomly throughout the genome and the direction of mutation is not random. The only way variation is seen as random is that it is random relative to the effect variation has on fitness. This study shows otherwise for a particular view of fitness.

    The major problem with this is that the precise meaning of fitness has not been settled. There is still a major debate about what exactly fitness is supposed to mean. Without a proper definition of fitness, we can’t really say what natural selection is. Also, without a proper definition of fitness we can’t really make any sense of how variation can be random relative to fitness in the first place. Of course some may still claim that "evolution is a blind, purposeless process is difficult to grasp, yet it is a fundamental part of understanding biology" or that Darwin's theory of random purposeless variation acted on by blind, purposeless natural selection. Such claims are now seen for what they really are, non-empirical claims based on metaphysics i.e. they are not empirically scientific.
    Last edited by Techne; 06-05-2012 at 08:46 PM.
    You can't trust a meta-ethical moral relativist since such a person can abuse reason to justify any act.


  5. #5
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    Of any number of mutations from 1 to 1 billion if one of them happens to offset the fitness (my understanding of the word) of any part of a sample even by just a mere 0.001% in favour of survival causing this change to amalgamate itself within the group through reproduction or replication over time then a "superior" genetic combination will more than likely (I say with more chance than none) become dominant due to the apparent advantage it will find itself in the environment especially when this change is received by many more organisms within the group through natural and passive process. It would also obviously reinforce itself over time, simple mathematics or even a simple experiment should dictate how a meagre advantage could still offset the balance of results in favour of the side with the advantage over a large repeated sample. Conversely a negative change of the same seemingly meagre effect would also be eradicated over time simply due to it negatively affecting the group for exactly the same reasons.

    Therefore I don't believe it is difficult to see how genetic information could branch out in favour of survivability via total randomness and how it could work in this way, well in a sense that in a swarm of a billion failures there may only be 1 success but a success would more than likely flourish nonetheless whereas the failures would not (Success = change more suited to the environment, Failure = change less suited to the environment). And also constantly changing environments, samples moving and/or growing to occupy larger areas and any factor or influence conceivable ranging from minor to extreme could cause these constant and ever occurring and evolving changes to result in more than one split within what may have started out as a small sample of one type of organism to many. Thus inevitably resulting in many different groupings of organisms in seemingly "perfect" arrangements as the process naturally refined itself towards the direction of success in each and every split that succeeded and saturated itself.

    The one question this raises is how some seemingly huge successes in larger organisms and creatures managed to find a 0.001% footing within the sequence of changes that ultimately made it what it is when seemingly there was no advantage to be had at its early stages. For instance how did some of these changes turn into a fully blown eye when surely it served no purpose in the very early stages and possibly had 0% advantage. Well perhaps it actually did serve a purpose in its extremely primitive state or wasn't quite what one might expect? Perhaps it evolved in a stubbornly nonsensical direction to a point and suddenly took off when it worked by chance? Perhaps the mutation was a little extreme to begin with? Another debate another time.

    Besides all that though and with my understanding being explained and be put on the line above, why can't an "evolutionary risk management strategy" type behaviour be just another self reinforcing genetic success picked up along the way just like any other function developed?
    Last edited by Bobbin; 07-05-2012 at 11:30 PM.
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  6. #6

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    Quote Originally Posted by Bobbin View Post
    Of any number of mutations from 1 to 1 billion if one of them happens to offset the fitness (my understanding of the word) of any part of a sample even by just a mere 0.001% in favour of survival causing this change to amalgamate itself within the group through reproduction or replication over time then a "superior" genetic combination will more than likely (I say with more chance than none) become dominant due to the apparent advantage it will find itself in the environment especially when this change is received by many more organisms within the group through natural and passive process. It would also obviously reinforce itself over time, simple mathematics or even a simple experiment should dictate how a meagre advantage could still offset the balance of results in favour of the side with the advantage over a large repeated sample. Conversely a negative change of the same seemingly meagre effect would also be eradicated over time simply due to it negatively affecting the group for exactly the same reasons.
    The logic of all this depends entirely on your definition of fitness. What is your understanding of the word taking into account that there is still a debate about what it actually means.

    Quote Originally Posted by Bobbin View Post
    Therefore I don't believe it is difficult to see how genetic information could branch out in favour of survivability via total randomness and how it could work in this way, well in a sense that in a swarm of a billion failures there may only be 1 success but a success would more than likely flourish nonetheless whereas the failures would not (Success = change more suited to the environment, Failure = change less suited to the environment). And also constantly changing environments, samples moving and/or growing to occupy larger areas and any factor or influence conceivable ranging from minor to extreme could cause these constant and ever occurring and evolving changes to result in more than one split within what may have started out as a small sample of one type of organism to many. Thus inevitably resulting in many different groupings of organisms in seemingly "perfect" arrangements as the process naturally refined itself towards the direction of success in each and every split that succeeded and saturated itself.
    Again, depends on your view of “fitness” and in this case, “randomness” as well. We know that mutations are not random (see above) and at best youo can argue that mutations are indeterminate. Indeterminacy does not imply randomness.

    Quote Originally Posted by Bobbin View Post
    Besides all that though and with my understanding being explained and be put on the line above, why can't an "evolutionary risk management strategy" type behaviour be just another self reinforcing genetic success picked up along the way just like any other function developed?
    Nobody said it this “evolutionary risk management strategy” is not a function gained via evolutionary change. However, it has to pointed out that functions and the propensity definition of fitness are irreducibly teleological features or qualities as explained previously.
    You can't trust a meta-ethical moral relativist since such a person can abuse reason to justify any act.


  7. #7

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    DNA can make errors during replication. This is a fact and has been observed.

    This error is the very definition of mutation as the code may not match in certain areas.
    For example, guanine is supposed to bond with cytosine but instead bonds adenine, that is an error. Sometimes they don't bond at all and removes some a base or adds cause frameshift errors.

    Frickin' cancer is a mutation.
    Techne the only people who believe it is not random are creationists and a tiny fraction of a few "scientists". A scientific hypothesis that is not regarded by the vast majority of other scientists is simply not science, it failed peer review and that's when I know its rubbish.
    If we were made from dirt, why is there still dirt?

  8. #8

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    Quote Originally Posted by boramk View Post
    DNA can make errors during replication. This is a fact and has been observed.

    This error is the very definition of mutation as the code may not match in certain areas.
    For example, guanine is supposed to bond with cytosine but instead bonds adenine, that is an error. Sometimes they don't bond at all and removes some a base or adds cause frameshift errors.

    Frickin' cancer is a mutation.
    Techne the only people who believe it is not random are creationists and a tiny fraction of a few "scientists". A scientific hypothesis that is not regarded by the vast majority of other scientists is simply not science, it failed peer review and that's when I know its rubbish.
    I get what you are trying to say, however, there are a few things that can be misread.

    For example, DNA cannot make errors. It is the replication machinery that sometimes do not make a 100% copy of the template DNA or the way DNA mutations are resolved by the DNA repair machinery. Sometimes a nucleotide undergoes a change on its own for example, cytosine can deaminate to uracil and this results in a mismatch (this mutation is sometimes induced as in the case of your immune system). There are different kinds of machinery the cell can employ to fix this change. Cytosine demaination can be resolved by at least 4 pathways (see figure):
    1) Copying of the base by high-fidelity polymerases during DNA replication.
    2) Short-Patch Base Excision Repair (SP-BER) by uracil-DNA glycosylase removal and subsequent repair of the base.
    3) Long-Patch Base Excision Repair (LP-BER)
    4) Mismatch repair (MMR)

    A different mechanism results in a different mutation. For example:
    1) Normal DNA replication results in a C:G→T:A transition.
    2) Successful SP-BER resolves the mutation, however the recruitment of error-prone translesion polymerases results (e.g. REV1) in transversions (REV1; C:G→G:C) and transition.
    3) LP-BER can also resolve the mutation, however recruitment of low-fidelity polymerases (e.g. Pol n) also causes transition and transversion mutations.
    4) MMR repair can also resolve the mutation, however the recruitment of low-fidelity polymerases through this pathway is a major cause of A:T transitions.

    So the mutation as a result of cytosine deamination is as a result of the way the mutation is resolved by the DNA replication or DNA repair machinery.


    "Error" is also not a definition of mutation. A DNA mutation is merely a change of one nucleotide to another i.e. a change in the nucleotide sequence.

    Regarding cancer, well there are good arguments that cancer is a new species and the process of carcinogenesis via somatic evolution of malignancy is a form of speciation.

    Regarding the randomness of mutations. It is actually a well known fact that mutations do not occur randomly in the genome, there are hotspots in every genome where mutations are more prone to happen (e.g. 5'-CG-3', see more examples in article linked above). The direction of mutation is nonrandom as transitions are more likely to happen than transversions. The rate or frequency of mutations is not random and is known for a wide variety of species and even different cells and cellular parts (e.g. mitochondrial DNA mutation is 10 times faster than nuclear DNA mutation in mammals).

    There is no real debate about this, mutations do not occur randomly with regards to location or frequency.

    The only way mutations are argued to be random is with regards to the fitness of an organism. The problem with this of course is (as mentioned above) that the exact definition of fitness is still being debated. Is fitness a causal propensity or merely a statistical effect? In any case, neither of these definitions lead to the view that mutations are random in any ontologically interesting level. At most it can be argued that mutations are indeterminate.
    You can't trust a meta-ethical moral relativist since such a person can abuse reason to justify any act.


  9. #9
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    Quote Originally Posted by Techne View Post
    The logic of all this depends entirely on your definition of fitness. What is your understanding of the word taking into account that there is still a debate about what it actually means.


    Again, depends on your view of “fitness” and in this case, “randomness” as well. We know that mutations are not random (see above) and at best youo can argue that mutations are indeterminate. Indeterminacy does not imply randomness.
    My understanding of the word fitness, which I admit could be entirely wrong but still fits nicely in context here, is the current measure of survival of a specific species. The current state of well being of a species or group not being measured against any sort of baseline because that would be rather subjective but by the effect of change within any given timeframe which should depict either a positive or negative stance toward survival when compared before and after the change.

    Randomness is just that :/ Complete random occurences. In light of this thread randomness would be an element that is constantly being shaped by my understanding of fitness above. A change (mutation) toward a more positive state of fitness being the most likely change that is kept which is surely also an autonomous logical phenomenon so it would seem to have direction and purpose even though it is sparked by a random event. That is of course if the event is not being influenced as I mentioned initially - in this case that is if an "evolutionary risk management strategy" type behaviour is just another self reinforcing genetic success picked up along the way just like any other function developed?
    If you're gonna be dumb you gotta be tough!

  10. #10

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    Quote Originally Posted by Bobbin View Post
    My understanding of the word fitness, which I admit could be entirely wrong but still fits nicely in context here, is the current measure of survival of a specific species. The current state of well being of a species or group not being measured against any sort of baseline because that would be rather subjective but by the effect of change within any given timeframe which should depict either a positive or negative stance toward survival when compared before and after the change.
    This account of fitness does not appear to be specific on whether it is some intrinsic propensity of an individual or just a non-causal statistical effect.

    Quote Originally Posted by Bobbin View Post
    Randomness is just that :/ Complete random occurences. In light of this thread randomness would be an element that is constantly being shaped by my understanding of fitness above. A change (mutation) toward a more positive state of fitness being the most likely change that is kept which is surely also an autonomous logical phenomenon so it would seem to have direction and purpose even though it is sparked by a random event. That is of course if the event is not being influenced as I mentioned initially - in this case that is if an "evolutionary risk management strategy" type behaviour is just another self reinforcing genetic success picked up along the way just like any other function developed?
    Randomness and indeterminacy are not the same. I think what you are referring to here is indeterminate event, not random events.
    You can't trust a meta-ethical moral relativist since such a person can abuse reason to justify any act.


  11. #11

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    And the debate continues... just because evolution is possible it's seen by some as the only possible way we all got here.

    Quote Originally Posted by bullzeye.za View Post
    ( But not on the standard intelligent design model, according to that, organisms will never change and have never changed )
    False: http://www.evolutionnews.org/2010/10...ign039121.html
    ID's biological aspect is a diversion on the standard evolutionary model (if there is such a thing) just like gradual evolution, punctuated equilibrium and Darwinism.

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