More non-random evolution

Have alook at radioactivity winds up evolution's clock:http://news.bmn.com/news/story?day=021001&story=2Qoute of the researchers:"Even more intruiging [..] those mutations occurred at positions which have been evolutinary 'hot spots' for the past 60000 years".Non-random mutations? Any comments? Remarks?Best wishes,
Peter

Dear percy,Radioactivity is assumed to act randomly in the genome with respect to mutations. This is also expected for UV and oxidative stress. Apparently it is not random, as demonstrated by these 'intruiging' findings. What's up? Theory in trouble?
Best wishes,
Peter

dear monkenstick,You say:
borger, perhaps we should stop trying to explain hotspots to you, because its clear you just don't get it.
are you suggesting that the mutations caused by radiation are "directed"?I say:
No, but due to radiation it may be so that the DNA is damaged and an SOS repair sytem is induced that mends the DNA by exchange with a piece of 'Junk DNA' and thus introduces the same nucleotide on the same spot all the time. At least that is a mechanism.You say:
or is it simply that some regions of the genome are more susceptible than others to radiation?I say:
What mechanism do you propose?best wishes.
Peter

Dear Taz,You write:
You say:I tried to explain the difference between probabilities to Peter in post 163 on this thread,
http://EvC Forum: molecular genetic proof against random mutation (1) -->EvC Forum: molecular genetic proof against random mutation (1)
but he did not seem to get it. I looked at the 1G5 gene in Genebank and PubMed and can not see what he thinks that he is proveing there either.
Peter, I will try to get back to you on both the 1G5 and the GLO gene/scurvy stuff later as I am swamped right now. One note, the rate of depletion of Ascorbate was described in one of the earlier reference papers that I posted for you earlier in the debate, it was a PDF concerning Ascorbate Bioavailability by Levine et al. in PNAS. The lactonase gene inactivation is wrong, not just because there is no mention of it anywhere in the literature, but because inactivation of the lactonase gene product would really screw up a number of other systems as well that an organism would be unlikely to survive (the pentose phosphate shunt for one).I say:Please do not make a straw man out of the GLO gene. I mentioned several times that I do not need it to demonstrate non-random mutations. That is demonstrated in the 1G5 gene. I also pointed out the implications of non-random mutations for molecular phylogeny in mail #184 in the 'molecular evidence against random mutation-thread'. In addition, it was you who introduced a putative alternative metabolic route for vit C, or a long storage capacity of vit c in the liver. Both mechanism make the gene redundant, and that was my initial claim. That the gene is redundant. According to the hypothesis of 'non-random mutations and a multipurpose genome', redundant genes will be readily inactivated over time, since they are not under selective constraint. That's what we find in primates. Okay, the inactivation is in the same spot, but that may be due to non-random mutations, or if you like 'hot spot' mutations as they are called in literature.best wishes,
Peter[This message has been edited by peter borger, 10-09-2002]

dear Dr Page,I looked up some mitochondrial sequences of several 'primates' and if you like to discuss them, be my guest (PNAS 2001, 98:537-542). I seems that 10 hotspots are present. And, as you know mtDNA doesn't have histons, so that cannot be the explanation. Intriguingly, all mutations are the same nucleotide. So, like the 1G5 gene these mutations are non-random with respect to position and nucleotide. I checked whether they could be 5-methylcytosine hotspots --that converts CG into TA-- and some of them are but the major part aren't. An ununderstood mechanism? I bet it is.Best wishes
Peter

Dear Percy,You say:
What was it about the earthquake analogy that you didn't understand, Peter? Like radiation, earthquakes also act randomly, but not all buildings have equal probability of falling because some are weaker than others.I say:
If so, than it is imaginable that mutations are always introduced at the same spot. And as observed in mtDNA of distinct primates and human subpopulations usually the same nucleotides are introduced. Thus, mutation is non-random with respect to these features and that would bring down the strongest argument for molecular evolution: sequence similarity.You:
I argued through analogy, while others have explicitly pointed out that some parts of the genome have structural susceptibility to change, and this has all been pointed out to you before.
Do you really believe that DNA is equally strong everywhere in the genome?I say:
Apparently mutations are introduced at 'hotspots' that are preserved in humans at least 60000 years. So, how can we discriminate between common descent and common mechanism (whether or not DNA structure related is irrelevant to this observation)?You say:
If so, then move the discussion forward by arguing for this point instead of continually restarting the same discussion from the beginning.I say:
Yes, let's have a close look at the mtDNA's in primates and human.best wishes,
Peter

Dear WI,Why all these why-questions? How can I do why questions, I'm only human.In the meantime it is a alternative explanation for alignment of mutations found in 'related' species. And maybe you find the evidence flimsy --that is it always how something new starts-- the evidence is NOT zero. So, I have a case.In the meantime I will think about all your why-questions.Thanks and Best wishes,
Peter

dear Quetzal,You say:
Actually, I'm getting a bit tired of the hotspot argument. You're off-base, Peter.I say:
So, because you are tired of this argument I am off base? I really do not see the logical link between these statements.You say:
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:I say:
That's a mechanism isn't it? I already proposed a similar mechanism in another mail.Your ref:
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)I say:
What does it say about mutational hotspots? I mean how are they introduced in the same spot? Nothing, except that they are slowly repaired.You 2nd ref:
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 say:
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.
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.You say:
I guess that's one more god/designer of the gaps argument down the toilet.I say:
Don't forget to wipe. You say:
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.I say:
Apparently, hotspots are associated with a repair mechanism. The same repair mechanisms can be found in all primates, so what's the point?I say:
Thanks for the contribution,
Peter

dear WJ,You say:
PB, your evidence for non-random, directed mutation is flimsy because the same data can be better explained by coventional evolutionary theory. The "why" questions relate to the discrepency between your "explanation" and observations.I say:
No, that's not the reason why it is flimsy. The reason is that only 5 primates have been scrutinised for the mutation in the GLO gene. As demonstrated for the 1G5 gene, the more sequence analysis the less likely common descent is because of shared non-random mutations. I explained this in letter #184, while you explicitly askes for it. Similarly, and as mentioned before, what I like to see are several sequences of several subpopulations of all primates? That would give compelling evidence.You say:
Using your non-random, directed mutation hypothesis some predictions can be made. One prediction would be that, if the common primate "stop" codon mutation in the GLO pseudogene is the result of directed, non-random mutation then the mechanism which has produced this mutation should also operate in other genomes and produce the same result. However the vast majority of mammalian genomes have not suffered lethal mutation of the GLO gene - they have functional GLO genes.I say:
It can be reasoned that these mechanisms are specific for primates, not for other families of mammals.You say:
Conventional evolutionary theory explains this pattern by a common ancestor for all primates - your hypothesis does not explain the pattern except by relegating it to an unknown mechanism operating identically in most primate genomes but not operating effectively in most mammals.I say:
All but --at least-- two primates.You say:
Why not test your hyothesis and evolutionary theory on another set of data? IIRC guinea pigs and some bats also have non-functional GLO pseudogenes. Your hypothesis would predict that the common primate mutation would also be expected to occur in those other pseudogenes because there is a non-random mutation mechanism acting.I say:
If guinea pigs have the same hotspots it would be found, indeed. However, I am afraid that they don't have the same hotspots. The guinea pig homologue of exon X demonstrates a huge deletion, so it is not tracable anymore.
Yes, I am setting up a non-falsifiable theory of creation. You say:
Evolutionary theory would predict that the fatal mutations in the other GLO pseudogenes have occured at random and are unlikely to be the same as the common primate mutation because there is no close common ancestor of the primates, guinea pig and bats.I say:
The group of the bats is very interesting, since they comprise also one family and I predict that within a family a similar mechanism is operable in all genomes that introduced non-random mutations. The sequencing of several (related) bats and subpopulations of them will provide compelling evidence.You say:
Therefore, if the common primate mutation is found in the other groups then this would be more supportive of your hypothesis; if the common primate mutation does not occur in the other groups then this would be strong evidence against your hypothesis and consistent with evolutionary theory.I say:
Strong evidence? Of course not, in distinct families there may be distinct hotspots, since hotspots are determined by the surrounding DNA sequence. So, different sequence different hotspots.You say:
PB, I fear that you are simply using a new incarnation of the god-of-the-gaps argument. We don't know precisely why certain mutations occur more frequently than other mutations therefore there is a directed mechanism which we haven't found therefore there is inteligent design of the mechanism therefore there is a creator.I say:
O yes, we do know. I gave already a couple of possible explanations. I don't need the god of the gaps to proof design. Let me reiterate the argument of "genetic redundancies". It is clear evidence that genes are in the genome without selective constraint, so there is no evolutionary argument how they could have evolved by mutation and selection. The major part of the protein coding genes in any organism is redundant. Like it or not, it points in the direction of design, not evolutionism. The rest is non-random mutation in a multipurpose genome.Best wishes,
Peter[This message has been edited by peter borger, 10-10-2002]

Dear Seebs,You say:
"This doesn't imply planning, design, or volition; it just recognizes that some structures break more easily than others."I say:
"Exactly, and that may contribute to the alignment of mutations in DNA. Such mutations may look like common descent."best wishes,
Peter[This message has been edited by peter borger, 10-10-2002]

Dear Dr Page,If you like to educate me, go ahead and provide me with the refernces and I will have a look at the methodology.
Convince me that you are right and try to overcome your condescending attitude. (And, I am still waiting for your apologies w.r.t to your false accusation).Best wishes,
Peter

Dear Quetzal,YOU wrote:quote:
--------------------------------------------------------------------------------
Q: Actually, I'm getting a bit tired of the hotspot argument. You're off-base, Peter.PB: So, because you are tired of this argument I am off base? I really do not see the logical link between these statements.--------------------------------------------------------------------------------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.MY RESPONSE:
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.
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.YOU:
quote:
--------------------------------------------------------------------------------
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:
PB: That's a mechanism isn't it? I already proposed a similar mechanism in another mail.--------------------------------------------------------------------------------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.MY RESPONSE:
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.YOU:
quote:
--------------------------------------------------------------------------------
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)
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.--------------------------------------------------------------------------------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.MY RESPONSE:
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.YOU:
quote:
--------------------------------------------------------------------------------
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".
IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.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.--------------------------------------------------------------------------------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.MY RESPONSE:
The mutations I talk about are NON-random with respect to nucleotide and position.YOU:
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.MY RESPONSE:
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?YOU:
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.MY RESPONSE:
But the could be present in the same kind of organisms. Family level or even higher levels.YOU:
quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------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.MY RESPONSE:
I gave you my definition of nonrandomness above. I do not need the ‘creation hypothesis’, as lined out above.YOU:
quote:
--------------------------------------------------------------------------------
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.PB: Apparently, hotspots are associated with a repair mechanism. The same repair mechanisms can be found in all primates, so what's the point?--------------------------------------------------------------------------------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).MY RESPONSE:
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.YOU:
What’s YOUR point about repair mechanisms and primates? Your statement is a complete non-sequitur.MY RESPONSE:
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.Best wishes,
Pet

dear Quetzal,YOU SAY:quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------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.I SAY:That remains to be seen.YOU SAY:quote:
--------------------------------------------------------------------------------
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 93,184, 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.
--------------------------------------------------------------------------------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.I SAY:
Thanks for the link to the paper. If you have a close look at table 1, and read it from top to bottom and concentrate on the positioned I mentioned before you will find out that the mutations on these spots are the same with respect to nucleotide. For instance, compared to CRS position 93 all mutations observed are T-->C transitions, independent of the organism. Similar, position 184, all C-->T; position 223, all C-->T; position 230, all A-->G; position 278, all C-->T; position 311, all C-->T; and position 387, all A-->G. They cannot all be explained by 5-methylcytosine hotspots (= a mechanism). So, my claim of non-randomness with respect to position and nucleotide is valid. Whether or not a mechanism is involved remains to be established. It should be noted that in a previous letter (to Mark24) I already mentioned that two types of mutations may exist, random and non-random. Here I present further evidence for this vision.YOU WRITE:quote:
--------------------------------------------------------------------------------
(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.
--------------------------------------------------------------------------------You seem to be saying that repair mechanisms cause mutation? This is a very odd assertion.I SAY:
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.YOU SAY: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?I SAY: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?You say:
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?I SAY:
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.YOU WRITE:quote:
--------------------------------------------------------------------------------
Q: Somehow I doubt that you read the article
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.--------------------------------------------------------------------------------Article, singular. Glad you admit you made the whole statement/question up out of whole cloth.quote:
--------------------------------------------------------------------------------
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".
IOW, Peter, there's no god/designer diddling with DNA - just a statistically higher likelihood of mutation caused chemical/structural idiosyncracies and crappy repair.PB: Whether or not these hotspots where designed cannot be concluded from the manuscripts. 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.--------------------------------------------------------------------------------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.I SAY:
Not the ONLY way. Another way involves common design through creation.YOU SAY:quote:
--------------------------------------------------------------------------------
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.
PB: The mutations I talk about are NON-random with respect to nucleotide and position.--------------------------------------------------------------------------------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.I SAY:
Apparently, this is not entirely true judging the 1G5 gene and the mtDNA sequences in subpopulations of humans and primates (see above).YOU SAY:quote:
--------------------------------------------------------------------------------
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.
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?--------------------------------------------------------------------------------Also in others, especially such things as ionizing radiation. Randomly, but with a non-exclusive affinity for certain sequences. Maybe (still under investigation).I SAY:
And that would make them NON-random mutations with respect to position and (possibly) nucleotide, isn’t it?YOU WRITE:quote:
--------------------------------------------------------------------------------
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.
PB: But the could be present in the same kind of organisms. Family level or even higher levels.--------------------------------------------------------------------------------Hunh?I SAY:
If the genomes have been created similarly (for instance the primates and human), than I expect that shared DNA sequences are equally prone to NON-random mutations. Thus, line up of mutations and an illusion of common descent.quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------Oh goody. I can hardly wait.quote:
--------------------------------------------------------------------------------
Q: What’s YOUR point about repair mechanisms and primates? Your statement is a complete non-sequitur.
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.--------------------------------------------------------------------------------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.I SAY:
I agree, it should be banned.YOU SAY:
As to the first — mutations are not caused by repair mechanisms. When you first mentioned this above, I thought I was misunderstanding you.I SAY:Read my explanation above.YOY SAY:You really don’t have a clue about basic biology, do you?I SAY...
...No comments.Best wishes,
Peter[This message has been edited by peter borger, 10-13-2002]

Dear Mammuthus,You say:
So as to let Quetzal continue this without distraction from me, I want to address only one point here. Your theory of repair based "non-randomness" is falisfied for mtDNA which do not have an established DNA repair machanism.I say:
So, the mechanism is nucleus dependent and/or similar to 5-methylcytosine hostpots. Both would result in alignment of non-random mutations.You say:
It also occurs to me that if you use your definition of non-randomness (though it has changed from time to time) , I should be able to pinpoint exactly the mutation in every somatic cell I have (germ cells as well of course) for any mutation just before it happens. Can you do this...where will the next mutation in my genome occur Peter if it is non-random? Easier question, where will the next mutation in my mtDNA HVI region occur?I say:
Most likely it would involve position 223 or position 311.Best wishes,
Peter

Dear Quetzal,YOU SAY: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.MY RESPONSE:
You don't have to be a genomic researcher. It is obvious from the sequences of the 1G5 gene and the mtDNA in subpopulations.YOU SAY:quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------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.MY RESPONSE:
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.YOU WRITE:quote:
--------------------------------------------------------------------------------
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?
--------------------------------------------------------------------------------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:quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------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.MY RESPONSE:
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.
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'.YOU WRITE:quote:
--------------------------------------------------------------------------------
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.
--------------------------------------------------------------------------------Quite simply, Peter, no we don't, and no it doesn't. You multiplied the assumptions beyond any reasonable explanatory power. Demonstrate your assertion...MY RESPONSE:
I supported my assertions several times. However, evolutionism also seems to have an 'explanation'. So, it will be my explanation against evolutionism's explanation.YOU WRITE:quote:
--------------------------------------------------------------------------------
Not the ONLY way. Another way involves common design through creation.
--------------------------------------------------------------------------------Please, please show us how creation/common design explains inheritance and the observations from population genetics.MY RESPONSE:
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.YOU WRITE:quote:
--------------------------------------------------------------------------------
And that would make them NON-random mutations with respect to position and (possibly) nucleotide, isn’t it?
--------------------------------------------------------------------------------Nope, it doesn't, unless you plan on completely redefining statistical probability along with your redefinition of random.MY RESPONSE:
Maybe we have to do that.Best wishes,
Peter[This message has been edited by peter borger, 10-14-2002]