More non-random evolution

Actually, I'm getting a bit tired of the hotspot argument. You're off-base, Peter.Here's one article that specifically directly links a human cancer mutational hotspot at codon 12 of K-ras to preferential DNA damage and poor repair:Denissenko, M., Pao, A., Pfeifer, G. and Tang, M-s. Slow repair of preferentially formed benzo(a)pyrene diol epoxide DNA adducts at the mutational hotspots in the human p53 gene. Oncogene 16:1241-1249 (1998)And here's another one (on line for all you cheapskates): Hatahet, Z., M Zhou, LJ Reha-Krantz, SW Morrical and SS Wallace. 1998. In search of a mutational hotspot PNAS 95: 8556-8561.Hotspots are caused by structural susceptibility at specific points on the DNA to specific mutagens. All evidence suggests that that it is simply a structural defect, and that location and surrounding codons have a major impact on whether a particular DNA site is a "hotspot" or "coldspot". IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.I guess that's one more god/designer of the gaps argument down the toilet.For those interested, here's the full PNAS article referenced in the OP: Natural radioactivity and human mitochondrial DNA mutations. Oddly enough, the article also talks about hotspots being more susceptible, and provides a neat comparison between evolutionary mutations and radiation-induced mutations at the same locus.

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Q: Actually, I'm getting a bit tired of the hotspot argument. You're off-base, Peter.

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PB: So, because you are tired of this argument I am off base? I really do not see the logical link between these statements.

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Nice irrelevancy. Actually, I’m simply tired of the way you consistently misinterpret and misunderstand the concept of randomness as relates to the existence of mutational hotspots. You are off-base because you are wrong.

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Q: Here's one article that specifically directly links a human cancer mutational hotspot at codon 12 of K-ras to preferential DNA damage and poor repair:

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PB: That's a mechanism isn't it? I already proposed a similar mechanism in another mail.

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No, you didn’t. You merely asserted that an idiosyncratic definition of non-randomness falsifies the theory of evolution. The only mechanism you’ve provided deals with undetectable morphogenetic fields that somehow magically transpose DNA elements from one spot on the genome to another and/or mystically change DNA structure in response to undefined environmental triggers. Not much of a mechanism.

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Denissenko, M., Pao, A., Pfeifer, G. and Tang, M-s. Slow repair of preferentially formed benzo(a)pyrene diol epoxide DNA adducts at the mutational hotspots in the human p53 gene. Oncogene 16:1241-1249 (1998)

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PB: What does it say about mutational hotspots? I mean how are they introduced in the same spot? Nothing, except that they are slowly repaired.

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Somehow I doubt that you read the article. It looks like all you did was pick up something out of the title. If you HAD read the article, you would know the answer to your question, because that’s precisely what the article talks about. However, for clarity: the BPDE mutagen (for example, from cigarette smoke), preferentially effects a specific spot — actually a single codon — in the p53 gene which controls proliferation, growth, and differentiation of normal cells. A mutation in this gene is one of the key factors determining whether other cell damage causes malignancy. The paper discusses how the mutagen effects the DNA strand. What’s most interesting to this discussion is the discovery that BPDE preferentially acts on a particular spot on the codon based on its location and the surrounding codons, rather than effecting the entire codon equally. This indicates that this particular spot has a chemical or structural weakness and that the normal cellular repair mechanisms are unequipped to repair it rapidly enough to prevent negative effects in all cases.

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Q: And here's another one (on line for all you cheapskates): Hatahet, Z., M Zhou, LJ Reha-Krantz, SW Morrical and SS Wallace. 1998. In search of a mutational hotspot PNAS 95: 8556-8561.
Hotspots are caused by structural susceptibility at specific points on the DNA to specific mutagens. All evidence suggests that that it is simply a structural defect, and that location and surrounding codons have a major impact on whether a particular DNA site is a "hotspot" or "coldspot".

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IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.

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PB: Whether or not these hotspots where designed cannot be concluded from the manucripts. However, the article shows that location and surrounding codons may have a decisive role in the outcome of the mutation. If so, than these mutations are non-random (hotspots), and since it may involve specific codons it clearly suggests a mechanism. Therefore, the alignment of mutations observed in related species may be due to such common mechanisms, instead of common descent.

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The mechanism that you keep harping on is a chemical/structural failure at that spot. It is no different than a rope with a flaw preferentially breaking at that flaw under strain. Environmental factors such as chemical mutagens are the strain that effects the DNA strand. Whereas the strain will be applied across the strand, only the weak point will be effected (or at least, will be effected first). It remains random (although statistically more probable) because it is impossible to predict a) when the mutation will occur; b) whether or not the particular mutagen WILL in fact effect the hotspot — it’s not guaranteed that simply the presence of the mutagen will have any effect at all; and c) whether or not the mutation will have any effect on the organism once it occurs — often it simply kills the cell. Hotspots DO NOT provide any support for your ridiculous assertion concerning non-randomness falsifying evolutionary theory, for the simple reason that a mutation at a specific hotspot remains random under the definition of the term as used in biology and genetics. Your continual attempts to redefine what random means are specious, at best.As far as common descent goes, mutational hotspots — weaknesses in the DNA rope — CAN be used if and only if the specific sequence that creates the hotspot is present in some organisms and not others. On the other hand, they DON’T provide support for common design for the same reason — the exact sequences aren’t present in every organism.

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And if you thought that in my opinion a designer was diddling with DNA as a directly measurable force than you didn't understand me properly. I rather use the genetic redundancies as an argument for design. The non-random mutations can be used to invalidate NDT and common descent.

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No, you prefer the supernatural morphogenetic field idea. Again, all you’re doing is redefining random as understood in evolutionary theory, then arguing against the Peter Borger Theory of Randomness. This is called the strawman fallacy. You have no evidence. You have no supporting documentation. You’re simply wrong, Peter, as every single one of the papers I and others have shown you proves.

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Q: For those interested, here's the full PNAS article referenced in the OP: Natural radioactivity and human mitochondrial DNA mutations. Oddly enough, the article also talks about hotspots being more susceptible, and provides a neat comparison between evolutionary mutations and radiation-induced mutations at the same locus.

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PB: Apparently, hotspots are associated with a repair mechanism. The same repair mechanisms can be found in all primates, so what's the point?

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My point was that the article lends additional weight to what I said about hotspots being points on the DNA strand that are more susceptible to particular environmental effects (in this case ionizing radiation). What’s YOUR point about repair mechanisms and primates? Your statement is a complete non-sequitur.

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Since my discovery of non-random mutations I checked some sequences and indeed there is non-random mutation with respect to nucleotide and position. So, let's redefine what a mean by non-randomness of mutations.

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Your discovery? Too funny — you really put your finger on the problem right there. You’re the only one to find this miracle anywhere. No wonder you want to redefine the terminology - it's the only way your assertions have any merit, even in your own mind.

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By non-random mutations I mean non-random with respect to i) type of nucleotide and ii) position where it is introduced. Whether or not there is a mechanism involved is at this point not relevant. This non-randomness can also be demonstrated for mtDNA (PNAS 2001, 98:537-542). A careful look shows non-random mutations on several position of the analyzed mtDNA fragment of 309 base pairs. To be exact, nucleotide positions 107, 184, 201, 223, 263, 264, 301, 307, 362, and 387 involve all this principle of non-random mutation: same nucleotide introduced on same spot, even in bonobo, neanderthaler and human subspecies. Now you have to give me a very good reason to insist on random mutation. MtDNA does not have histons, and I already checked for 5-methyl-cysteine hotspots. Some of them are, the majority isn't.

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I must have missed something. Please indicate specifically where in this paper on human phylogeny you cite, Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins there is any indication of non-random mutations. All the paper is talking about are divergent mtDNA genomes as a basis for re-assessing the validity of mtDNA phylogenies. It basically calls into question the timing of the out of Africa hypothesis. I included a link to the full paper in the hopes that Dr. T or Mammuthus might take a glance at it and address your specific contention concerning the nucleotide positions. To me, it certainly appears you are jumping WAY out on a limb using this paper as support for the existence of non-random mutations.

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(Reference mechanisms)
I already gave a possible explanation in a previous letter. It was something like this: In response to DNA damage an SOS repair mechanism is activated that mends the DNA thereby introducing the same mutations on the same spot. Since the same families have the same repair mechanism and related DNA sequences the nucleotides are non-randomly replaced, and that may give the illusion of common descent. And, you have misunderstood my assumption of morphogenetic fields. By this I mean ‘creaton (virtual particles) interaction with matter in a morphogenetic field (earth) that give rise to genes’. It merely explains the sudden appearance of new gene families in organism during ‘evolution’. You may abbreviate it to ‘creaton interaction’ or ‘creat-ion’ (pronounce: creation), if you like. I don’t need this mechanism to explain shared mutations between related species.

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You seem to be saying that repair mechanisms cause mutation? This is a very odd assertion. As to the creaton particles: what the heck are these? And what is morphogenetic field (earth) supposed to mean? Is it something like N-rays? Congratulations, you’ve actually gone beyond even creationism to something straight out of New Age pseudoscience. Of COURSE you can provide evidence that these magical particles and fields exist? I mean, they’ve been detected, right? There is some journal somewhere that’s got published articles we can read?

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Q: Somehow I doubt that you read the article

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PB: I didn’t read them yet, but I though ‘why not respond for the sake of discussion’. Today, I looked them up and will read them over the weekend.

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Article, singular. Glad you admit you made the whole statement/question up out of whole cloth.

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Q: And here's another one (on line for all you cheapskates): Hatahet, Z., M Zhou, LJ Reha-Krantz, SW Morrical and SS Wallace. 1998. In search of a mutational hotspot PNAS 95: 8556-8561.
Hotspots are caused by structural susceptibility at specific points on the DNA to specific mutagens. All evidence suggests that that it is simply a structural defect, and that location and surrounding codons have a major impact on whether a particular DNA site is a "hotspot" or "coldspot".

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IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.

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PB: Whether or not these hotspots where designed cannot be concluded from the manucripts. However, the article shows that location and surrounding codons may have a decisive role in the outcome of the mutation. If so, than these mutations are non-random (hotspots), and since it may involve specific codons it clearly suggests a mechanism. Therefore, the alignment of mutations observed in related species may be due to such common mechanisms, instead of common descent.

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However, the specific sequences, which ARE inherited, are what cause the hotspots in the first place. If they weren’t inherited, the next generation wouldn’t have them. A particular hotspot shared between two different species means the two species share a common sequence. Since the ONLY way they can share a common sequence is by inheritance, the two species share a common ancestor. You can twist and turn on this as much as you want, it doesn’t change the fact.

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Q: The mechanism that you keep harping on is a chemical/structural failure at that spot. It is no different than a rope with a flaw preferentially breaking at that flaw under strain.

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PB: The mutations I talk about are NON-random with respect to nucleotide and position.

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Nope, wrong again. This assertion only stands if the particular environmental factor ONLY effects a particular spot on the genome 100% of the time. This isn’t the case. A mutagen, for example, CAN effect basically anywhere on a genome. However, there is often a chemical affinity for a particular point. At that particular point, it may be slightly MORE likely to cause a mutation. However, there’s no 100% guarantee. Hence, mutations remain random with respect to location, time, effect, or even IF.

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Q: Environmental factors such as chemical mutagens are the strain that effects the DNA strand. Whereas the strain will be applied across the strand, only the weak point will be effected (or at least, will be effected first). It remains random (although statistically more probable) because it is impossible to predict a) when the mutation will occur; b) whether or not the particular mutagen WILL in fact effect the hotspot — it’s not guaranteed that simply the presence of the mutagen will have any effect at all; and c) whether or not the mutation will have any effect on the organism once it occurs — often it simply kills the cell. Hotspots DO NOT provide any support for your ridiculous assertion concerning non-randomness falsifying evolutionary theory, for the simple reason that a mutation at a specific hotspot remains random under the definition of the term as used in biology and genetics. Your continual attempts to redefine what random means are specious, at best.

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PB: Apparently, hotspots introduced by these mutagens have a different repair mechanisms. Questions: do you think that these mutagens induce only hotspot-mutations in the p53 gene or also in other genes? Randomly? Or dependent on DNA sequence?

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Also in others, especially such things as ionizing radiation. Randomly, but with a non-exclusive affinity for certain sequences. Maybe (still under investigation).

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Q: As far as common descent goes, mutational hotspots — weaknesses in the DNA rope — CAN be used if and only if the specific sequence that creates the hotspot is present in some organisms and not others. On the other hand, they DON’T provide support for common design for the same reason — the exact sequences aren’t present in every organism.

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PB: But the could be present in the same kind of organisms. Family level or even higher levels.

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Hunh?

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Apparently the hotspots are induced by a specific external chemical and induced a particular repair response. I will elaborate on this matter next week, first spell out the article on this topic.

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Oh goody. I can hardly wait.

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Q: What’s YOUR point about repair mechanisms and primates? Your statement is a complete non-sequitur.

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PB: If the hotspots are associated with repair mechanism and these repair mechanism are similar/same in all primates, than I also expect the mutagen to induce the same kind of mutations in --let’s say-- human, chimps, bonobo’s.

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I’d say the latter part about mutagens is quite likely — in fact, is observed. That’s why experiments on primates are usually so indicative. The cruelty to animals folks does tend to put a crimp in experimentation, though. As to the first — mutations are not caused by repair mechanisms. When you first mentioned this above, I thought I was misunderstanding you. You really don’t have a clue about basic biology, do you?

Hmm, we seem to be getting the same arguments on two different threads.Again, with reference to Table 1 in the link I posted, I am not a genomics researcher. I hope that one of our experts here will take a look and provide a more substantive response.

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Actually, what I say is that aspecific damage to DNA (by radiation, oxidation, etc) will be repaired, and that the repair mechanism may introduce the same nucleotide on the same spot over and over. This induces the illusion of common descent. Moreover, if comparable mechanisms exist as observed with 5-methylcytosine induced C-->T transitions than this may also contribute to the illusion of common descent.

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You are aware, of course, that one of the most common point mutations is C-->T deamination? It's usually repaired fairly easily by glycosylase. There are at least 8 different kinds of glycosylase for example - each one repairing a particular kind of base damage. Basically, every single mutation requires a distinct, seperate mechanism for repair. Only when these already-present repair mechanisms fail or are overwhelmed is there mutation that carries over. IOW, repair means it puts the DNA strand back together just like it was. OF COURSE it introduces the same nucleotide during repair - or the same sequence of nucleotides. There's no other way it CAN repair. I think you're missunderstanding how DNA repair works.

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I only introduced the idea of a creatons interacting with matter in a morphogenetic field to explain new genes. Evolutionism cannot explain them, this view can. What the heck is a creaton? What the heck is a graviton? I guess nobody knows. Except that gravitons transmit gravitation. Similarly, creatons convey creation. Did you really expect the Creator to be a bearded man on a cloud?

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Yet there is no evidence anywhere in any literature that indicates that genes have been poofed into existence de novo in response to environmental changes. Quoting from my response to this assertion in the other thread in case you missed it:

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There is absolutely no evidence for this assertion. Please show one single study, with references, on any population of any organism, where the introduction of a new pathogen, mutagen, or environmental factor produced fortuitous variation that allowed the population to adapt to the new conditions.

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Unlike, for instance, the possible existence of the hypothetical graviton particle - which is inferred from the obvious fact that two masses exert an attraction on each other - there is NO evidence of any kind that your creatons and morphogenetic fields exist.

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Like gravitons, they have not been detected. But they can be inferred from what we see. We see sudden appearance of new genes, new organisms in the genetic and fossil record: creaton interactions in a morphogenetic field (earth) elegantly explain this. For clarity, I do not need this hypothesis to explain common mutations, since the can be explained by non-random mechanisms.

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Quite simply, Peter, no we don't, and no it doesn't. You multiplied the assumptions beyond any reasonable explanatory power. Demonstrate your assertion...

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Not the ONLY way. Another way involves common design through creation.

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Please, please show us how creation/common design explains inheritance and the observations from population genetics.

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And that would make them NON-random mutations with respect to position and (possibly) nucleotide, isn’t it?

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Nope, it doesn't, unless you plan on completely redefining statistical probability along with your redefinition of random.

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You don't have to be a genomic researcher. It is obvious from the sequences of the 1G5 gene and the mtDNA in subpopulations.

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It is quite easy to make assertions. Anyone — expert or not — can do that. However, to counter the assertions it is often necessary to have in-depth expertise. This is one of those times. I simply don’t have the background necessary to argue this point. I’m sure someone else does.

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Q: You are aware, of course, that one of the most common point mutations is C-->T deamination? It's usually repaired fairly easily by glycosylase. There are at least 8 different kinds of glycosylase for example - each one repairing a particular kind of base damage. Basically, every single mutation requires a distinct, seperate mechanism for repair. Only when these already-present repair mechanisms fail or are overwhelmed is there mutation that carries over. IOW, repair means it puts the DNA strand back together just like it was. OF COURSE it introduces the same nucleotide during repair - or the same sequence of nucleotides. There's no other way it CAN repair. I think you're missunderstanding how DNA repair works.

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PB: In addition to this mechanism that always introduces C-->T tranversions, there is also the mechanism of C--> tranversions due to 5-methylcytosine conversions. After reading your reference, I realised there is another mecahnism involved in generation of oxidative stress induced mutations. As described by Hatahet et al (PNAS 1998, 95:8556) there is a consensus sequence that modulate the frequency of misincorporation 8-oxoguanine by DNA polymerase. This mechanism is also likely to contribute to the illusion of common descent. In particular in mtDNA sequences. Finally, it is becoming increasingly evident that junk DNA may be used to repair DNA (Nature Genetic JUNE 2002, if I recall properly) and may also lead to the introduction of the same nucleotide on th same spot.

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Actually, the mechanism repairs C-->T deamination errors. If you’ll check, I think you’ll find that 5-methylcytosine is implicated in G-->T mispairing. The glycosylases TDG or MBD4 are the specifics for repair of this particular error. You seem to be confusing repair mechanisms such as the glycosylases with the mutagens that cause the problem in the first place. On another note, here’s a good article on the repair of 8-oxo-G errors: Substrate specificity and Reaction Mechanisms of Murine 8-Oxoguanine-DNA glycosylase.Please provide the full reference for the article you cite. If you're going to use something as evidence, we need to be able to check it.

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No evidence? Whole families of new genes show up in the genomic record. If I'm correct, this is Tranquility Base's major point. The sudden appearance of such new gene families in organisms should be sufficient evidence.

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If you really want me to completely falsify and overturn evolution theory, let me know, and I will present the example of an organism that are gentically identical without being a clone. So, this organism can be interpreted as being created yesterday, last year, last century, whenever. It hasn't been published in peer reviewed journals (for the obvious reason), but a book on the topic was published in 2000. It is the final blow to evolution theory, and strong support for the hypothesis of 'creation of a multipurpose genome'.

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You are merely repeating your assertion. I wouldn’t bank too much on TB’s sudden appearance, as he has yet to show any evidence for this. I’d say the obvious reason your amazing discovery hasn’t been published in the literature is because it doesn’t exist. What book? And why a book and not a journal? The great Evilutionist Conspiracy again?You have failed to answer the question, so I’ll repeat it:

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Q: There is absolutely no evidence for this assertion. Please show one single study, with references, on any population of any organism, where the introduction of a new pathogen, mutagen, or environmental factor produced fortuitous variation that allowed the population to adapt to the new conditions.

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I supported my assertions several times. However, evolutionism also seems to have an 'explanation'. So, it will be my explanation against evolutionism's explanation.

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You have consistently failed to support your assertion. You’ve merely repeated it ad nauseum and then dragged in pointless details that have no bearing on your contention. If there’s evidence, present it. Reveal your magical organism. I promise I won’t steal your Nobel Prize.

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In the multipurpose genome 'all' genes that contribute to variation are already present. Variation is induces by genetic elements that affect gene regulation --and therefore gene expression--, and probably shuffle from one place in the genome to another. All observations of population genetics can be explained since it only involves (regulation of) frequencies of alleles. If populations get isolated they may 'speciate' due to loss and/or shuffling of genes. Furthermore, entropy acting on the genome can account for all degenerative observations in the genome (for instance, the inactivation of genes that are more or less redundant). Finally, mechanisms that introduce mutations non-randomly can explain the illusion of common descent.

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Once again, you’re simply repeating your assertion concerning multipurpose genomes without evidence. Your first part is simply a restatement (simplistically, and leaving out a number of different mechanisms btw) of the random mutation part of RM&NS. The last bit about entropy and degenerative observations doesn’t make any sense. Finally, you have NOT shown that non-random mutations exist — only that you have absolutely no idea what random means in statistics.

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Q: Nope, it doesn't, unless you plan on completely redefining statistical probability along with your redefinition of random.

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PB: Maybe we have to do that.

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Wow — you’re really reaching now, Peter. Gonna re-invent mathematics as well as evolution? Okay — please show the probability equations you propose that overturn current understanding of statistics.[edited for clarity, 'cause there were two back-to-back quotes and it wasn't obvious who said what to whom. ][This message has been edited by Quetzal, 10-15-2002]