molecular genetic proof against random mutation (1)

Dear Mark,
I agree with you on:
"The statistical definition of "random", as it pertains to nucleotide sequences, is specifically that each site has an equal chance of mutation."However, I do not agree to
"Since there are hot spots where the chance of mutation is higher, mutations are therefore non-random where hot-spots exist. However, every site does have a chance of mutation, & you cannot predict where the next mutation will occur, so it is random in that sense."Because hotspots imply a mechanism. And a mechanism implies involvement of RNA and/or proteins. Besides, I already mailed (somewhere) that at least two mechanism may be implicated in mutation. Firstly, there is a random mechanisms. Probably, the oxydative stress induced mutations is random (I expect this from the random nature of oxygen-radicals). Secondly, there may be a environment directed rearrangement and/or mutation of DNA sequences. Nobody has found the underlying mechanism(s) yet, but that is not so surprising since the major part of the proteins of any organism is still unknown. In my opinion, the mechansims will be hard to elucidate (and that is why they have not been observed yet), because the proteins involved do not have a direct measurable function.You say that:
"You seem to be claiming that mutations are non-random in the statistical sense, then dropping the statistical definition for a more colloquial one, meaning non-random is deliberate, rather than just not-of-an-equal-chance."Indeed, since I think there is a (protein and/or RNA mediated) mechanism involved. I do not mean that the mutation has been introduced deliberately on that spot. Because we do not know the undelying mechanism(s) we do not recognize it as non-random. As soon as the mechanisms are elucidated we will recognize it as non-random. As long as these studies are performed between species we will never be able to elucidate the mechanism. What we need to look at is between and within subspecies (as the Drosophila example). That will provide clarity.
Similarly, I always wondered why in hematological disorders (leukemia's) often involve exactly the same chromosomal translocations in the same genes and independent of the population. It implies a mechanism."You cannot conflate the two definitions to suit yourself."I don't."There isn't a random chance that a car of a particular colour will be next to drive down my road, does that therefore infer that a creator is "deciding" what colour car will be next down my street?"That's not what I mean. I mean that if a non-random mechanism is operable to generate mutations in genes in response to the environemt it makes it hard not to believe in design.Best wishes,
Peter

Dear Mark,
Why are bananas bended?
I already mentioned that science is not interested in why-questions, it's metaphysics.
As soon as we find out the mechanism underlying hotspots, we can discuss this in more detail. And I am not jumping the gun, that is what evolutionists do. Ever read the "selfish gene"? That is one big jumping-to-conclusion-book. As long as we do not know the DNA molecule, I will object to that.
Furthermore I demonstrated that the NDT is not valid at the molecular level. What else do you need to be convinced? Proof against natural selection? I will not give that here, but I recommend you to follow the literature carefully.
Best wishes,
Peter

Dear John,
As a matter of fact bananas are bent by gravity.
Cheers,
Peter

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[This message has been edited by peter borger, 07-24-2002]

dear mark,You wonder:
"But you ARE jumping the gun. You don't know why hot spots exist, yet they are evidence of design????? How?"If mutations are (environmentally) directed than the information to do this was already present in the genome. (See also Fred's letters.)Question: How do evolutionist's conceive hotspots?Peter

Dear Mark,You say about hot spots:
"They don't conceive them, they describe them. Without further evidence, they would be jumping the gun."Mutational hot spots imply non-randomness. And non-randomness suggests (at least) the involvement of a mechanism. Either protein or RNA mediated. It is proof against NDT, since the primary tenet of NDT is random mutation.
Best wishes
Peter

dear Mark,Thanks for your summary of what Futuyma has to say on the subject:"Mutations occur at random." Indeed here it says: "RANDOM!!!!!"but next...:"It is extremely important to understand (WELL I DO NOT, SINCE THE FORTHCOMING IS CONTRADICTING THE PREVIOUS!!!)what this statement does & does not mean. It does not mean that all conceivable mutations are equally likely to occur, because, as we have noted, the developmental foundations for some imaginable transformations do not exist. It does not mean that all loci, or regions within a locus, are equally mutable, for geneticists have described differences in mutation rates, at both the phenotypic & molecular levels, among & within loci (Woodruff et al. 1983; Wolf et al. 1989)."...it says: "but not really RANDOM"So, what he says is that mutations are random but not really. Come on, I do not buy a theory that says: Something is but not really. Open up your eyes, Mark, don't you see that he set up a theory that cannot be falsified (And still the 1G5 gene falsifies the theory).AND:
"It does not mean that environmental factors cannot influence mutation rates: ultraviolet & other radiation, as well as various chemical mutagens & poor nutrition, do indeed increase rates of mutation."I agree to this."Mutation is random in two senses. First, although we may be able to predict the probability that a certain mutation will occur, we cannot predict which of a large number of gene copies will undergo the mutation. The spontaneous process of mutation is stochastic rather than deterministic. Second, and more importantly, mutation is random in the sense that the chance that a particular mutation will occur is not influenced by whether or not the organism is in an environment in which that mutation would be advantageous"These are axiomata of NDT. It does not have to be true.Have a nice day,Peter

dear mark,You say:
"If you divided a year up into 1 minute time slots, then measured precipiation at a particular point on land, you would find that precipitation is non-random. Does that mean God makes it rain? By your logic it does."I say:
Distortion of my words, and also a fallacy. In logic this type of reasoning is called an "extension", and belongs to the type of "faulty analogies". A faulty analogy is an inappropriate comparison or an attempt to compare two or more dissimilar things.
So, this can never be used as an argument.You say:
"A genetic example would be the formation of chiasmata for crossing over as recombination occurs. This isn’t random either, it happens more often in GC rich parts of the genome."I say:
Excellent example. It demonstrates that a mechanism is operating and thus the process is NON-RANDOM.And:
"However, we know this, so is this evidence of design."Yes, since the variation that is generated by this mechanism is already present and encoded in the DNA.Peter

Dear Gene,You say:
"Your argument is that, if the location on the genome where mutations occur are stastically weighted, they are necessarily encoded by God."Not only statitically weighted, but the mechanism that introduces the mutations is present in the genome and, therefore, has been encoded by the programmer.And:
"His argument is that if something "random" but statistically weighted is necessarily from God, as you assert, then precipitation is necessarily from God because it is statistically weighted in a very similar manner."This is not true. The introduction of mutations is NOT random since it seems to be introduced by some sort of mechanism that has been programmed in the DNA. This is what I am trying to convey. Likewise, the degradation of a protein (encoded in the DNA) by a protease also (encoded in the DNA) is non-random (this is a proper analogy). Therefore, you are not allowed to compare non-random protein-mediated (?) mutation with random --though statitically weighted-- precipitation.Peter

dear Mark,You say:
"Futuyma has clearly set out what random means in the context of RM&NS. Using THAT DEFINITION OF RANDOM, mutations at hotspots ARE random in the sense that the locus for any particular mutation cannot be deterministically predicted, OK? It’s not a difficult concept. So, no, the NDT isn’t expecting you to buy something that is random but not really. IF YOU APPLY THE GIVEN DEFINITION, AND THAT DEFINITION ONLY!!!!!!!!"For the last time:
Since the mechanism is unknown --and the mechanism is currently not known-- but there are more and more genes that do not change at random, but rather subject to the environment (directed evolution). This falsifies NDT, since the first tenet is randomness independent from the environment. As soon as the mechanism is elucidated we will be able to predict where mutations are introduced. For clarity's sake, imagine the time before the discovery of the genetic code. How was DNA related to protein? Nobody knew, since the mechanism was unknown. Now we know the relationship between DNA and protein since we know the mechanisms involved (including the code, transcription and translation)
For the rest you keep repeating yourself that mutations are random since they cannot be predicted. I simply state that as soon as we know the underlying mechanism, i.e. if we know how the specific proteins integrate/replace nucleotides in the 1G5 gene (and other genes) we will be able to know where they occur and maybe we will also know when these proteins are induced. Maybe in respons to DNA damage, particular environmental factors for which they have receptors, or whatever. I don't know. All I say is that the gene does not change at random with respect to nucleotide substitions.
You seem to be to stuck to Futuyma's definitions. In addition, he does not give me a plausible explanation for mutational hotspots. And he cannot introduce that they are protein/RNA mediated for obvious reasons.
Apparently, you are the only one who is still fighting the non-random mutations in the 1G5 gene. Why?Peter

dear Brad,You write:"Can you say then in Verne Grant's ideas from plants generalized with or without Stebbins, what is the measure of a difference of genetic variation and genetic difference per any genome that can be tested in actual populations? without prejudicing such things as the potential vegatative contribution to polypoloidy factors that even in terms of multiplication of species are often down played ?? The mutation rate is largely irrelevant to this way of framing the question I have remarked as you note yet a simple notion of the environment and future environmental chnages is not adequete in the answer where the internal and external "variable" needs denotation. I do not have the actual assement of this connotation which is the reason I ask a second time. Sincerely, Brad."Could you please be more clear. (What is Verne Grant's idea and Stebbins?) And, what exactly do you want to know? Thanks,
Peter

dear mark,You state:"Think about it, every loci in a sequence has a probability of mutation. Therefore, regardless of your degree of knowledge on the subject, you cannot make a deterministic prediction about the next mutation."First of all, I did not DENY that there are random mutations (see previous mails, this is inevitable since all DNA is subject to oxydative stress and it will lead to degenaration of the genome). Bit, in addition, there are also NON-RANDOM protein and/or RNA directed mutations. Since they are mediated by some molecule encoded in the DNA, the information is present already. If this all evolved naturalisticly, then I expect an explanation from you how you see this. (one that goes beyond: "organism evolving this mechanism have a better chance to survive in a changing environment", since I am able to invent such non-contributing stories myself).Presently there is no reason to NOT assume that eventually we will be able to predict where they will be introduced. Similarly, it is thought that antibody improvement is also random. But, since a protein-mediated mechanism is involved I really doubt that. What we observe as random may as well be non-random. (why do I have to repeat myself again and again?)And you state:
"See above, re. Random mutation & your hope that you will be able to predict mutations.quote:
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Originally posted by peter borger:Maybe in respons to DNA damage, particular environmental factors for which they have receptors, or whatever. I don't know. All I say is that the gene does not change at random with respect to nucleotide substitions.
--------------------------------------------------------------------------------Yes they do!!!!!!!!!! Good grief, man. What have I been labouring this past week?I say:
You've been trying to tell me that mutations are random. I do not (entirely) agree to your opinion, since I demonstrated that some genes change non-randomly and that falsifies NDT. I recommended you to carefully study the 1G5 gene but --I have the feeling-- that you simply don't do that (it is the first figure in the first mailing in the thread: "molecular genetic proof against random mutations". Read what Percy has to say on it, and see all my responses).
If you had, you wouldn't bring forward the same questions/arguments over and over and over. Luckily, I am very patient.Furthermore:
"That you don’t like Futuymas definition is tough.It’s like having a conversation about transport, where I define transport as anything that moves people about. You then say that you have falsified my contention that slaves were transported across the Atlantic, because YOUR definition of transport is the motor car. And they don’t float.I say:
Where do you find all these inappropriate analogies? I really like them. I am not going to discuss definitions (it's a debating trick). All I did was falsify NDT in its current state.Furthermore:quote:
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Originally posted by peter borger:You seem to be to stuck to Futuyma's definitions.
--------------------------------------------------------------------------------Because Futuyma is taking the time to describe the meaning of random as it pertains to evolution. That is the intended meaning, & I will stick to it.I’m sure you will stick to the statistical defintion of random, despite it NOT being the intended meaning."I say:
"Listen, Mark, maybe NDT's definitions need to be updated. Maybe Futuyma has to explain how he thinks about the mechanism behind hotspots and non-random mutations. That would clear things up. (It is not my fault that NDT is in trouble)".In response to my qoute:
quote:
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Originally posted by peter borger:In addition, he does not give me a plausible explanation for mutational hotspots.--------------------------------------------------------------------------------You say:
"Neither have you provided me with one."I say:
Here you demonstrate that you don't listen beyond your own paradigm.And you state:
"Adaptive evolution is caused by random mutation culled by natural selection.Becomes..Adaptive evolution is caused by all loci being subject to the probability of mutation, that mutation being culled by natural selection.So what? It’s hardly falsified, is it?"I say:HARDLY isn't synonymous to NOT.
(Thanks for admitting NDT has been falsified).Best wishes,
peter

Dear SLPx,Thanks for the references.They clearly demonstrate that the mutations are protein mediated. It remains to be established in what degree the environment directs the induction of these genes. But, as demonstrated by some of your references rec-enzymes are induced, so it does not falsify my assertions but rather provides further evidence for NON-RANDOM, protein directed mutations (in response to environmental change). Thanks, for the examples.
Maybe you could point out where ecactly these abtracts falsify NONRANDOM mechanisms. For instance, "genome wide" does not mean that it is random, rather that mutations can be found in several genes throughout the genome.
You really have to come up with better examples to claim falsification over mine (show me the sequences of a mutated gene in several subspecies of the organism after stationary phase).
Cheers,Peter

dear SLPx,I did not claim that nomads still have a functional GLO. Read what I had to say on the topic below:"In the evolutionary community the shared retroviruses are commonly regarded as evidence of common descent. However, this may only be superficial.
First there is the claim that they do not serve any purpose. That should be scientifically proven. Maybe their function cannot be deduced from knocking them out, but that does not say anything about their function, since you can knock out genes with an open reading frame without any effect on the organism (genetic redundancies). Secondly, I would like to see the complete DNA sequences within the species and between the species before jumping to conclusions.
I checked one claim about the GLO gene (the gene that catalyses the final step in vitamin c synthesis) that has been inactivated in the same spot in primates and is taken as proof for common ancestry. And, indeed a superficial look would immediately convince any evolutionist. However, if you have a careful look at the sequence you will discover that the replacement of nucleotides is not at random between the distinct species. Secondly, you will discover that it does not make a difference for the mutation rate of this gene whether it is functional or not, in contrast to what evolution theory would predict. Thirdly, it violated population genetics: why would the inactivated gene become fixed in the entire population, while the active gene conveys longivity. In addition, evolution never compensated for vitamin C uptake in the gut, and, finally, the gene is redundant anyway since the third step in vit c synthesis already yields vitamin C by spontenaous oxidation. Also not unimportant, at least 2 primates are able to synthesise vitamin c in the liver, indicating the presence of an intact GLO gene (I once had a discussion about this gene with Dr D. Theobald (Talk Origin) so I know a bit about pseudogenes. However, at this level it is mostly speculation since we do not know a lot about it, yet).
In analogy to vestiges (appendix, tonsils) that shouldn't have a function according to evolution theory, it is far too early to say that this is proof for common descent. Show me the DNA sequences of these retroviruses in chimp and man, and I will respond in more detail.
Retrotransposons may have a function in epigenic regulation of gene expression (actually there is some proof for that. See: Dr. E. Max's website Talk Origin. Another one regulates the aghouti colour of fur in mice). It is thought that they may also play a role in eye colour (human), and some diseases like schizophrenia, and B.-W.-syndrome.
Evolutionists are free to claim these genes as evidence for common descent (as they did -- and still do -- for genetic redundancies, but which has actually contributed to the fall of natural selection). I foresee that ultimately there will be an unforeseen solution to these "vestiges".So what I claimed was:
"the third step in vit c synthesis already yields vitamin C by spontenaous oxidation." The amounts are sufficient to prevent scurvy!Therefore the GLO gene --which does the fourth and final step in vit C synthesis-- is redundant!!!!!Reference: http//yarchive.net/med/vitamin_c.htmlBest Wishes,
Peter[This message has been edited by peter borger, 08-22-2002]

Dear SLPx,In response to pointing out the scientific evidence for me you reply:"I don't know whethyer I admire or am disgusted by this common quality in creatinists - taking something that is clearly evidence against their position and claiming that, in reality, it supports it. Strange..."There can only be two reasons for not responding to my question:1) You do not know the content of your refernces,
2) You do not understand the content of your references.If this is the case, do not hesitate to ask.Best wishes,
Peter

dear Tazimus,Thanks for your mail. I will check it out.
However, --according to my information-- cessation of biosynthesis in humans can result from two different gene defects. Firstly, through inactivation of the GLO gene that specifies an enzyme that converts the final step that involves an enzyme (step 4 in your reference). Secondly, trough a defect in the lactonase gene, that specifies a gene that converts the 3rd step in your reference.
The lactonase defect prevents any vitamin C synthesis at all, while the defect in the GLO gene still yields measurable amounts of vit C, because the substrate will spontaneously decompose to 2-keto-gulono-gamma-lactone in the presence of oxygen (this step in normally carried out by GLO gene product). The final step is a spontaneaous conversion to vit C (Thus, there are two spontaneous steps in the presence of oxygen). So, the only difference --if you don't express the GLO gene-- is speed of production. If one has an active lactonase gene spontaneous Vit C productions are around 15-20 mg/day. Sufficient levels to prevent scurvy.Best wishes,
Peter