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Author Topic:   More non-random evolution
peter borger
Member (Idle past 7665 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 17 of 67 (19468)
10-10-2002 12:54 AM
Reply to: Message 7 by Quetzal
10-09-2002 6:04 AM


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

This message is a reply to:
 Message 7 by Quetzal, posted 10-09-2002 6:04 AM Quetzal has replied

Replies to this message:
 Message 23 by Quetzal, posted 10-10-2002 4:31 AM peter borger has replied

wj
Inactive Member


Message 18 of 67 (19470)
10-10-2002 1:14 AM
Reply to: Message 16 by peter borger
10-09-2002 11:55 PM


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.
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. 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.
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. 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. 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.
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.
BTW it's WJ.

This message is a reply to:
 Message 16 by peter borger, posted 10-09-2002 11:55 PM peter borger has replied

Replies to this message:
 Message 19 by peter borger, posted 10-10-2002 1:53 AM wj has not replied

peter borger
Member (Idle past 7665 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 19 of 67 (19474)
10-10-2002 1:53 AM
Reply to: Message 18 by wj
10-10-2002 1:14 AM


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]

This message is a reply to:
 Message 18 by wj, posted 10-10-2002 1:14 AM wj has not replied

seebs
Inactive Member


Message 20 of 67 (19477)
10-10-2002 2:34 AM
Reply to: Message 4 by peter borger
10-08-2002 10:05 PM


quote:
Originally posted by peter borger:
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

I think you're misunderstanding the use of the term "random".
If I roll two dice, and add them, I get 7 more often than 12. This doesn't mean the dice aren't random; it means that there is a structure within which these random events are being pooled.
Imagine that you have an object which is weaker in some places and stronger in others. Now, hit it at a random point, and it may or may not break... Keep hitting it at random points. It is more likely that it will break at a weak place than a strong place, even though the places you hit it are random.
This doesn't imply planning, design, or volition; it just recognizes that some structures break more easily than others.

This message is a reply to:
 Message 4 by peter borger, posted 10-08-2002 10:05 PM peter borger has replied

Replies to this message:
 Message 21 by peter borger, posted 10-10-2002 2:43 AM seebs has replied

peter borger
Member (Idle past 7665 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 21 of 67 (19478)
10-10-2002 2:43 AM
Reply to: Message 20 by seebs
10-10-2002 2:34 AM


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]

This message is a reply to:
 Message 20 by seebs, posted 10-10-2002 2:34 AM seebs has replied

Replies to this message:
 Message 22 by seebs, posted 10-10-2002 4:14 AM peter borger has not replied
 Message 25 by Peter, posted 10-10-2002 8:34 AM peter borger has not replied
 Message 28 by derwood, posted 10-10-2002 1:08 PM peter borger has replied

seebs
Inactive Member


Message 22 of 67 (19483)
10-10-2002 4:14 AM
Reply to: Message 21 by peter borger
10-10-2002 2:43 AM


quote:
Originally posted by peter borger:
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."

I don't think so at all. Imagine that any of a dozen mutations can occur at a given point. It would be *VERY* suspicious to claim that two creatures (A and B) each have the same sequence for the first 11 of them, and B and C have only 2 in common, but A and B don't have a common ancestor, they just *HAPPENED* to have such an unlikely sequence happen.
If I deal two bridge hands, and someone ends up with the same set of cards both times, it's pretty hard to claim that the two starting sets of cards weren't similar.
I think I see where you're going, and if there were only one suspiciously similar sequence of genes in one related species, it'd be a good enough argument to cast it into doubt. When instead we have hundreds upon hundreds of sequences across hundreds of species... That's different.
It should be easy enough to test. Give one set of people access to a nicely detailed summary of the fossil record for a given chunk of the tree. Ask them to guess at relationships.
Now give another people a set of gene maps, and ask them to guess at the relationships.
If they come up with similar trees, we've got pretty good evidence that that's the best model.

This message is a reply to:
 Message 21 by peter borger, posted 10-10-2002 2:43 AM peter borger has not replied

Quetzal
Member (Idle past 5871 days)
Posts: 3228
Joined: 01-09-2002


Message 23 of 67 (19485)
10-10-2002 4:31 AM
Reply to: Message 17 by peter borger
10-10-2002 12:54 AM


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

This message is a reply to:
 Message 17 by peter borger, posted 10-10-2002 12:54 AM peter borger has replied

Replies to this message:
 Message 24 by Mammuthus, posted 10-10-2002 6:38 AM Quetzal has not replied
 Message 31 by peter borger, posted 10-11-2002 3:23 AM Quetzal has replied

Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 24 of 67 (19493)
10-10-2002 6:38 AM
Reply to: Message 23 by Quetzal
10-10-2002 4:31 AM


Hi Quetzal,
If you go to the "Endosymbiotic theory wrong" thread, Peter has fleshed out a bit more of his hypothesis, though the spurious defintion he uses of "non random" persists. Just to give you a heads up. The posting traffic here is increasing and it is getting harder (for me at least) to keep up with the various threads.
Cheers,
M

This message is a reply to:
 Message 23 by Quetzal, posted 10-10-2002 4:31 AM Quetzal has not replied

Peter
Member (Idle past 1478 days)
Posts: 2161
From: Cambridgeshire, UK.
Joined: 02-05-2002


Message 25 of 67 (19501)
10-10-2002 8:34 AM
Reply to: Message 21 by peter borger
10-10-2002 2:43 AM


If I understand you you are saying that a preferential
mutation mechanism could be responsible for the apparent
similiarity in primate genomes.
So there was no common ancestor, but each kind of primate
evolved the same way due to this mechanism.
This mechanism, however, operates differently in different
kinds of animals.
So primates are more closely related to one another than
to bovines.
Does this mean that you believe that diverse groups of primates
are all evolving to a common end point?
How does the presence of such a mechanism allow for
the diversity that we see in primates (let alone life
on Earth)?
It seems to me that your arguments support common ancestry better
than any concepts of design.
We have a group of creatures (the primates) that at some time
in the past were all so similar that they have genomic hotspots
in the same areas, that have changed in similar ways. They also
must have hotspots in different areas to one another, and these
have changed in different ways.
At best this devolves to the same difficulty that Tranquility Base
points out that common descent and common design are hard to
differentiate.

This message is a reply to:
 Message 21 by peter borger, posted 10-10-2002 2:43 AM peter borger has not replied

derwood
Member (Idle past 1875 days)
Posts: 1457
Joined: 12-27-2001


Message 26 of 67 (19515)
10-10-2002 10:41 AM


I am still waiting for you to explain why all gene trees are supposed to be identical.
Afterall, someone with such an in depth knowledge of genomics and gene activity should be able to explain off the top of his head...

Percy
Member
Posts: 22389
From: New Hampshire
Joined: 12-23-2000
Member Rating: 5.2


Message 27 of 67 (19516)
10-10-2002 10:51 AM
Reply to: Message 14 by peter borger
10-09-2002 10:32 PM


peter borger writes:

If so, than it is imaginable that mutations are always introduced at the same spot.
Always? That would be wildly improbable. In the human genome there are literally thousands and thousands of places where a mutation might be more likely to occur than the average for loci across the whole genome. All you can say is that some loci are more likely than others to experience a mutation. Mutations can still occur at unlikely locations. Going back to the earthquake analogy, the stronger building is less likely to fall than other buildings, but it is still possible for it to fall while other weaker buildings remain standing. There are no certainties with earthquakes and radiation, only probabilities.

And as observed in mtDNA of distinct primates and human subpopulations usually the same nucleotides are introduced.
There are a wide variety of mutation types, and this only covers one of them. Limiting my comments only to nucleotide substitution, I could accept a tendency toward the same nucleotides being introduced, but saying "usually the same nucleotides are introduced" feels a bit too strong to me. This tendency has two natural origins:
  • Biochemical. Nucleotide substitutions are affected or limited by the rules governing biochemical reactions.
  • Filtering. Some nucleotide substitutions result in expression within the organism of characteristics inconsistent with survival and/or reproduction.
In order to add a supernatural possibility to this list you have to show that at least some mutational tendencies are not explained by these two possibilities.

Thus, mutation is non-random with respect to these features and that would bring down the strongest argument for molecular evolution: sequence similarity.
I don't think you mean to say that it "brings down the strongest argument for molecular evolution." Didn't you mean to say it brings down the strongest argument for common descent?
Anyway, it is only non-random in the sense that what happens is limited by natural laws. When I throw a rock repeatedly into the air at precisely the same angle and speed, the time it takes to fall is non-random, because gravity always acts the same way. When you subject the same biochemical repeatedly to the identical situation, what happens is always the same thing and is non-random, because the laws governing chemical reactions are always the same. Only if you repeated the same biochemical experiment over and over again getting different results each time might it be considered evidence of divine direction. And of course, radiation is the wildcard in this mix. How it "knocks out" a chemcial bond is random, dependent upon precisely where the radiation strikes.

So, how can we discriminate between common descent and common mechanism (whether or not DNA structure related is irrelevant to this observation)?
I hope that the inductions made about the descent of human sub-groups were not made by following single mutational lines. The fewer mutational lines used to determine descent pathways, the less likely they are to be correct, precisely for the reasons you mention, that for a single mutational line it would not necessarily be possible to differentiate between common descent and common mechanism.
But I don't want to lose sight of your original point when you began this thread, which cited an article about radiation causing increased mutational rates at genomic "hotspots". There is nothing non-random about this. Once again revisiting the earthquake scenario, you shake a city harder and the rate at which the weaker buildings fall increases. You radiationally bombard a genome harder, and the rate at which the weaker loci mutate increases.
--Percy

This message is a reply to:
 Message 14 by peter borger, posted 10-09-2002 10:32 PM peter borger has not replied

derwood
Member (Idle past 1875 days)
Posts: 1457
Joined: 12-27-2001


Message 28 of 67 (19531)
10-10-2002 1:08 PM
Reply to: Message 21 by peter borger
10-10-2002 2:43 AM


quote:
Originally posted by peter borger:
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]

Shame for Peter that there are TESTED methodologies employed to distinguish between homoplasy and phylogenetic signal.
But you must know that, being as well read as you are...

This message is a reply to:
 Message 21 by peter borger, posted 10-10-2002 2:43 AM peter borger has replied

Replies to this message:
 Message 30 by peter borger, posted 10-10-2002 10:15 PM derwood has replied

Dr_Tazimus_maximus
Member (Idle past 3216 days)
Posts: 402
From: Gaithersburg, MD, USA
Joined: 03-19-2002


Message 29 of 67 (19567)
10-10-2002 4:22 PM
Reply to: Message 12 by peter borger
10-09-2002 9:29 PM


quote:
Originally posted by peter borger:
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 true,a lthough you also mentioned that it contained directed mutations (which no one else appeared to see) so it is somewhat relevant.
quote:
That is demonstrated in the 1G5 gene.
I should be in the NIH library Monday, I was going to go today but I did not feel like trudging through the rain carrying a stack of papers.
quote:
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.
OK, I need to call you on this one. Please see your posts 101 and 105 here
EvC Forum: molecular genetic proof against random mutation (1)
you were making claims that went against every single thing ever published concerning ascorbic acid metabolism, which I then pointed out to you.
quote:
Both mechanism make the gene redundant, and that was my initial claim.
This is in error. If your claims concerning the mutation of the lactonase gene and the chemical conversion of the first hydroxyl were correct, and they do not appear to be as you have provided absolutely no suporting data while I have provided a few references that are contrary to your assertions, than yes it would be redundant. However, they are not, and if you had read the PNAS paper that I posted to you concerning the bioavailability study you would have noted that, after a long lag period where ascorbic acid stored in the liver was slowley released into the system, that thepatients suffered a precipitous drop in serum ascorbate levels indicating the onset of real scurvy. A long storage is not equivalent to a lack of requirement. GLO is not and never has been redundent. In primates it is lacking which is different.
quote:
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.
OK, I can see one of a pair of redundent genes having more mutations due to the selective constraint, however this STILL does not point to directed mutation. It points to a filtering process. And you still do not seem to understand hot spots. There is a MASSIVE difference between an increased probability of a specific event and a directed event. Your examples appear to me (I still need to check 1G5) to be far better explained bythe former than the latter.
By the way, you did not give a source for your mutational accumulation rates concerning rat and primate GLO genes that you posted in the other thread (the one that I cited earlier). Care to share?
------------------
"Chance favors the prepared mind." L. Pasteur
Taz

This message is a reply to:
 Message 12 by peter borger, posted 10-09-2002 9:29 PM peter borger has not replied

peter borger
Member (Idle past 7665 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 30 of 67 (19593)
10-10-2002 10:15 PM
Reply to: Message 28 by derwood
10-10-2002 1:08 PM


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

This message is a reply to:
 Message 28 by derwood, posted 10-10-2002 1:08 PM derwood has replied

Replies to this message:
 Message 34 by derwood, posted 10-11-2002 10:50 AM peter borger has not replied

peter borger
Member (Idle past 7665 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 31 of 67 (19606)
10-11-2002 3:23 AM
Reply to: Message 23 by Quetzal
10-10-2002 4:31 AM


Dear Quetzal,
YOU wrote:
quote:
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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.
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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.
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:
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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:
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.
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:
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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)
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.
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:
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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".
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.
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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.
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:
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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.
MY RESPONSE:
I gave you my definition of nonrandomness above. I do not need the ‘creation hypothesis’, as lined out above.
YOU:
quote:
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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.
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).
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

This message is a reply to:
 Message 23 by Quetzal, posted 10-10-2002 4:31 AM Quetzal has replied

Replies to this message:
 Message 32 by Mammuthus, posted 10-11-2002 4:21 AM peter borger has replied
 Message 33 by Quetzal, posted 10-11-2002 10:12 AM peter borger has replied

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