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Author Topic:   Darwin in the Genome
caporale
Inactive Member


Message 1 of 185 (28100)
12-30-2002 8:23 AM


In doing a search on another topic, I came across the thread on this forum regarding molecular evolution. I have just written a book on this topic, discussing the effect of natural selection on the mechanisms that generate genome variation [which is affected by a whole range og biochemical activities, from polymerases to proofreading to mismatch and other repair, to the sizes of nucleotide pools, to recombination].
I have come to the conclusion that through natural selection, many mutations move away from being completely random.
It is important to note that it was not Darwin who suggested that variation was generated by completely random changes in DNA, and, in fact, the concept that the mechanisms that generate genome variation fall under natural selection not only is consistent with the Darwinian framework, but also gives us a deeper sense of the potential power of natural selection.
For those interested in more detail, there is a links page at http://www.DarwinGenome.info that includes other writing on this subject, including the conference volume "Molecular Strategies in Biological Evolution". There also will be a review in the 2003 volume of Annual Reviews of Microbiology.

Replies to this message:
 Message 2 by peter borger, posted 12-30-2002 6:50 PM caporale has not replied
 Message 5 by Brad McFall, posted 12-31-2002 3:13 PM caporale has not replied
 Message 15 by PaulK, posted 01-10-2003 2:13 PM caporale has not replied

peter borger
Member (Idle past 7782 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 2 of 185 (28146)
12-30-2002 6:50 PM
Reply to: Message 1 by caporale
12-30-2002 8:23 AM


Dear Caporale,
C: In doing a search on another topic, I came across the thread on this forum regarding molecular evolution. I have just written a book on this topic, discussing the effect of natural selection on the mechanisms that generate genome variation [which is affected by a whole range og biochemical activities, from polymerases to proofreading to mismatch and other repair, to the sizes of nucleotide pools, to recombination].
I have come to the conclusion that through natural selection, many mutations move away from being completely random.
PB: Could you please be so kind to share with us briefly how you arrived at this conclusion.
C: It is important to note that it was not Darwin who suggested that variation was generated by completely random changes in DNA, and, in fact, the concept that the mechanisms that generate genome variation fall under natural selection not only is consistent with the Darwinian framework, but also gives us a deeper sense of the potential power of natural selection.
For those interested in more detail, there is a links page at http://www.DarwinGenome.info that includes other writing on this subject, including the conference volume "Molecular Strategies in Biological Evolution". There also will be a review in the 2003 volume of Annual Reviews of Microbiology.
PB: Could you please be so kind to provide the issue number.
Best wishes,
Peter

This message is a reply to:
 Message 1 by caporale, posted 12-30-2002 8:23 AM caporale has not replied

Replies to this message:
 Message 6 by Primordial Egg, posted 01-09-2003 12:30 PM peter borger has replied

caporale
Inactive Member


Message 3 of 185 (28150)
12-30-2002 8:54 PM


I am sorry to have been so cryptic about how I came to this conclusion-- to discuss it fully took a whole book.
Here are three examples of nonrandom mutation:
1)generation of diversity in the immune response.
while this occurs within a generation, it suggests the availabilty of biochemical mechanisms that can focus mutation: recombination is focused on moving a selection of variable regions next to the constant region. Secondly, the variable region "hypermutates" in a way that is sequence dependent, i.e. sequences such as RGYW [shorthand for A or G, G, T or C, A or T] are hotspots of mutation through a focused biochemical mechanism that is just being worked out.
2) repeat sequences in bacteria: for example, tetranucleotide repeats tend to grow and shrink at a comparatively high rate as the 2 strands of DNA misalign. These sequences have become enriched in so-called "contingency genes" which tend to be involved in rapid adaptation to a host.
3) a hotspot of recombination in the mammalian germ line appears to be in the histocompatibility region; while high variation in this region is a problem for transplant surgeons, it would be of selective value in evolution for protection against pathogens.
"Molecular Strategies in Biological Evolution" is volume 870 of the Annals of the New York Academy of Sciences. My introductory chapter to the volume is available at http://www.amazon.com/...3311936/excerpt/103-6490997-6923024
It is important to emphasize again that non-random mutation is fully consistent with the Darwinian framework of variation followed by selection-- in this case variation of the mechanisms that generate variation.

Replies to this message:
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Brad McFall
Member (Idle past 5150 days)
Posts: 3428
From: Ithaca,NY, USA
Joined: 12-20-2001


Message 4 of 185 (28215)
12-31-2002 3:07 PM
Reply to: Message 3 by caporale
12-30-2002 8:54 PM


My views on the evolution of immunity may be even more cryptic and perhaps the following info should make up its own thread-- this is just the "teaser":
Using this towards "cracking" the code:
Immunology as a generalization of Helmholtz's position @Faraday "shoulder" on 'chemcial quantivalence' is the macromolecular response of life-cycles where different gravity gradients are circumstpected and is but the scoped(out) tract of already changing base-pair transient (binomial expandable) strength communities.
Health may be improved if the entropy characteristics (Mendel on character OR factor) nonetheless (in being) irreversible) {in the process} are engineered into the organismic cycle between any point mutation possible in this particular phenomena of disease and THROUGH the chemical bond to physical (action at a distance) to any contact (visual or otherwise) and all reproduction not counterindicating orthogenesis however onto the macro-molecular--post-ribosome expression. These new entropy measures (from immunology) must occurr spatially (hence Helmholtz conception of the motion involved in the electrotonic state is too local a concept) both BEFORE the expression (in the nature of the gene) and after the-nature-of-the-genes-participating-UNIFORMLY.
1)Associate a singularity (electrotonic affordance) electrotonically {by an as of yet newly possible technological advane} of parallel computation connecting genome database and form-making made by (here is where the proprietary info goes)of every base pair of all organisms in the phenomena
2)By smaller scaling circles decrease the engieered sigularity perimeter into correspondence with biological reality and acutal macrothermodynamics of imunological aggregates
3)build scalable nano-structures of the space so involved to search/sort based on the above equality made between DNA (NOT AN A PERIODIC CRYSTAL)and form and BODY-ANTIBODY.
I assert that the two different scaled phenomena stem from the same cause but becuse we only tend to analyze levels of organization with the microscopic vs macroscopic distintion what Gladyshev divided and then asked for a Darwinization of may be one and the same thing but over a few more orders of magnitude one then we tend to find the words supporting.

This message is a reply to:
 Message 3 by caporale, posted 12-30-2002 8:54 PM caporale has not replied

Brad McFall
Member (Idle past 5150 days)
Posts: 3428
From: Ithaca,NY, USA
Joined: 12-20-2001


Message 5 of 185 (28216)
12-31-2002 3:13 PM
Reply to: Message 1 by caporale
12-30-2002 8:23 AM


Do you have any information on the "small diffusive effects" that are involved with your note?
It is also important to understand that Galton was able to possibly see what Darwin did not and short such diffusion being THE ANSWER can see many other possibilites for continutiy that must be required on this view. Correct me if I am wrong but I have always tended to feel that the continumm hypothesis in Math is something that goes hand and/in foot with your noted reasoning but because some physicists disgree fundamentally about/on the spatial *topology* of the universe there tends to occur a disconnect before biologists get to address this outside of particular sub(specialized) disciplines??

This message is a reply to:
 Message 1 by caporale, posted 12-30-2002 8:23 AM caporale has not replied

Primordial Egg
Inactive Member


Message 6 of 185 (28745)
01-09-2003 12:30 PM
Reply to: Message 2 by peter borger
12-30-2002 6:50 PM


Hi Peter,
Could you explain (in layman's terms hopefully) why "non-random" mutations bring down NDT?
Thanks
PE

This message is a reply to:
 Message 2 by peter borger, posted 12-30-2002 6:50 PM peter borger has replied

Replies to this message:
 Message 7 by peter borger, posted 01-09-2003 6:31 PM Primordial Egg has replied

peter borger
Member (Idle past 7782 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 7 of 185 (28759)
01-09-2003 6:31 PM
Reply to: Message 6 by Primordial Egg
01-09-2003 12:30 PM


Dear Primordial,
Essentially, Neodarwinian theory holds that evolution = random mutation plus natural selection. If these pillars cannot hold than the theory of evolution has no foundation, and all explanations that rely on it are invalid.
Now NON-RANDOM mutations have been scientifically proven the NDT is false. In another thread I also demonstrated that natural selection is highly doubtful for the evolution and maintenance of genetic redundancies. So, both pillars of NDT are invalid at the molecular level. It explains a lot.
Best wishes,
Peter
[This message has been edited by peter borger, 01-09-2003]

This message is a reply to:
 Message 6 by Primordial Egg, posted 01-09-2003 12:30 PM Primordial Egg has replied

Replies to this message:
 Message 11 by Primordial Egg, posted 01-10-2003 4:49 AM peter borger has replied

caporale
Inactive Member


Message 8 of 185 (28767)
01-09-2003 7:43 PM


Just to clarify an important point: Darwin and Wallace proposed that evolution takes place by selection acting on variation. They did not know the mechanisms that generate variation. Therefore, that some mutations may become more likely than others would not at all violate Darwin and Wallace's framework, but rather illustrate that variations in the mechanisms that generate variation can fall under natural selection, much as variations in wings and beaks can.

Replies to this message:
 Message 9 by peter borger, posted 01-09-2003 8:11 PM caporale has not replied
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peter borger
Member (Idle past 7782 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 9 of 185 (28768)
01-09-2003 8:11 PM
Reply to: Message 8 by caporale
01-09-2003 7:43 PM


Dear Lynn,
LC: Just to clarify an important point: Darwin and Wallace proposed that evolution takes place by selection acting on variation. They did not know the mechanisms that generate variation. Therefore, that some mutations may become more likely than others would not at all violate Darwin and Wallace's framework, but rather illustrate that variations in the mechanisms that generate variation can fall under natural selection, much as variations in wings and beaks can.
PB: I agree, Darwin and Wallace discovered the multipurpose genome.
Best wishes,
Peter

This message is a reply to:
 Message 8 by caporale, posted 01-09-2003 7:43 PM caporale has not replied

Replies to this message:
 Message 10 by Andya Primanda, posted 01-10-2003 2:14 AM peter borger has replied

Andya Primanda
Inactive Member


Message 10 of 185 (28782)
01-10-2003 2:14 AM
Reply to: Message 9 by peter borger
01-09-2003 8:11 PM


Say, Dr Borger, does your theory acknowledge common descent? If not, how do you explain the fossil record and the taxonomic hierarchy in nature?

This message is a reply to:
 Message 9 by peter borger, posted 01-09-2003 8:11 PM peter borger has replied

Replies to this message:
 Message 12 by peter borger, posted 01-10-2003 5:29 AM Andya Primanda has replied

Primordial Egg
Inactive Member


Message 11 of 185 (28787)
01-10-2003 4:49 AM
Reply to: Message 7 by peter borger
01-09-2003 6:31 PM


Peter,
quote:
Essentially, Neodarwinian theory holds that evolution = random mutation plus natural selection. If these pillars cannot hold than the theory of evolution has no foundation, and all explanations that rely on it are invalid.
I was under the impression that the Neo-Darwinian synthesis was about the marriage of evolution (natural selection with variation) and genetics. I haven't been able to find a definition which states that random mutation at the level of the genome is essential for NDT, maybe you could point me to a definition (see qu 1 below)?
Indeed, from looking at Dr Carporale's comments on this thread, and the synopsis of the book it seems to suggest to me that there are deeper level natural selection mechanisms working on the genome itself, which, if anything, seems to strengthen the Darwinian paradigm.
(From the synopsis:
It appears that genomes tend to endure when their most likely mutations create effective responses to their most likely challenges. Thus frequent mutation in the area of the genome that encodes the immune system, for example, is likely to be beneficial, whereas changes that encode for "housekeeping" functions of the organism, such as respiration, can quickly be fatal. The ability to focus mutation in certain parts of the genome and keep it away from other parts enables the organism to "pre-adapt" to forthcoming changes in its environment, greatly accelerating its evolution. In fact, all of these molecular strategies are powerful drivers of evolution, as natural selection operates upon them, spurring organisms to become more efficient at evolving. Thus genome structure emerges from seeming randomness. Caporale explains all these mechanisms dynamically with rigor and clarity. She also spells out their greater implications, including the importance of diversity for survival (our own diversity, plus general biodiversity), the possibility of new types of targets for medicine (attacking the "strategies" of microbes and tumors), and the need for caution in the face of proposals to "fix" "errors" in a human genome. Most importantly, by exploring the genome and its evolutionary strategies in wonderful detail, Caporale disperses the nagging doubt that natural selection could have produced human life unassisted. Indeed, the exciting work going on right now in this area opens our minds to this possibility and strengthens the Darwinian paradigm.
)
...and I'm guessing here, but from the very title of the book and the synopsis / Dr C's website (looks to be down at the minute - it was fine yesterday) that evolutionary (NS + variation) pressures are detected in the mutations themselves, suggesting some kind of higher order darwinian process going on - analagous to the fact that evolution itself is not a random process, but arises as a result of random mutations and selection. In the same way, "non-random" mutations in themselves arise from random mechanisms + variation (can someone correct me if I've misunderstood anything here?), via mechanisms which I gather are discussed in the book.
So a few questions to clarify my understanding:
1) What is the reasoning / background behind your assertion that NDT requires random mutations at the level of the genome?
2) If non-random mutations were an emergent property of random processes + NS occuring at a different scale (for want of a better word) then how would this affect your conjecture?
3) Does your conjecture point to design? If so, how is this different from Paley's blind watchmaker idea applied to non-random mutations?
4) To be honest, its very difficult to see where you make a clear summary of your entire conjectural edifice - NRM, the multi-purpose genome and the "Grand Unified Theory of Biology". I don't know what it is you refer to. Would it be possible for you to describe the salient points of the whole shebang, (or at least point me to the relevant posts) - or at the very least provide a working definition of the terms?
PE
------------------
Skeptical scrutiny is the means, in both science and religion, by which deep thoughts can be winnowed from deep nonsense - Carl Sagan

This message is a reply to:
 Message 7 by peter borger, posted 01-09-2003 6:31 PM peter borger has replied

Replies to this message:
 Message 13 by peter borger, posted 01-10-2003 5:32 AM Primordial Egg has replied
 Message 32 by Brad McFall, posted 01-13-2003 9:49 PM Primordial Egg has not replied

peter borger
Member (Idle past 7782 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 12 of 185 (28788)
01-10-2003 5:29 AM
Reply to: Message 10 by Andya Primanda
01-10-2003 2:14 AM


Dear Andaya,
AP: Say, Dr Borger, does your theory acknowledge common descent? If not, how do you explain the fossil record and the taxonomic hierarchy in nature?
PB: Common descent from archetypes? Yes.
Best wishes,
Peter

This message is a reply to:
 Message 10 by Andya Primanda, posted 01-10-2003 2:14 AM Andya Primanda has replied

Replies to this message:
 Message 17 by Andya Primanda, posted 01-10-2003 10:18 PM peter borger has replied

peter borger
Member (Idle past 7782 days)
Posts: 965
From: australia
Joined: 07-05-2002


Message 13 of 185 (28789)
01-10-2003 5:32 AM
Reply to: Message 11 by Primordial Egg
01-10-2003 4:49 AM


Dear PE,
I read Dr Caporale's book. I know what it holds and I know what it implicates,
Best wishes,
Peter

This message is a reply to:
 Message 11 by Primordial Egg, posted 01-10-2003 4:49 AM Primordial Egg has replied

Replies to this message:
 Message 14 by Primordial Egg, posted 01-10-2003 6:05 AM peter borger has replied

Primordial Egg
Inactive Member


Message 14 of 185 (28790)
01-10-2003 6:05 AM
Reply to: Message 13 by peter borger
01-10-2003 5:32 AM


quote:
Originally posted by peter borger:
Dear PE,
I read Dr Caporale's book. I know what it holds and I know what it implicates,
Best wishes,
Peter

and are you able to share this knowledge? I'm sure Dr Caporale would be interested.
PE
edit typos
PS is this your response to my questions?
[This message has been edited by Primordial Egg, 01-10-2003]

This message is a reply to:
 Message 13 by peter borger, posted 01-10-2003 5:32 AM peter borger has replied

Replies to this message:
 Message 23 by peter borger, posted 01-12-2003 8:11 PM Primordial Egg has replied

PaulK
Member
Posts: 17857
Joined: 01-10-2003
Member Rating: 3.9


Message 15 of 185 (28824)
01-10-2003 2:13 PM
Reply to: Message 1 by caporale
12-30-2002 8:23 AM


It is good to see the author of a book appear in the discussion. I hope that if I get something wrong I will be corrected.
So far as "random mutations" go the idea important to the theory is usually summed up as "random with regard to fitness". Dawkins discusses this in _The Blind Watchmaker (chapter 11) although he doesn't use that phrase. So this isn't new.
The mechanisms in _Darwin in the Genome_ do mean modifying this view a bit. They do bias the mutations that happen in favour of mutations which MIGHT be useful. Although they can also produce mutations which are clearly detrimental like Huntington's disease. However, in a more important sense the mutations are STILL random with respect to fitness. By this I mean that the probability that a particular mutation will happen remains the same whether or not it would, in fact, be useful in the current environment.
In the end I think that this book both makes things easier and more difficult for evolution in the public arena. The mechanisms discovered make evolution more plausible because they improve the odds of getting useful mutations. But the origins of these mechanisms will need ot be explained - a big research project.
For scientists however, this must be a very exciting set of findings. New understanding of how mutations occur as well as a big challenging research project to consider. One possibility that might be worth investigating is the relationship, if any, between the development of these mechanisms and the Cambrian "Explosion".

This message is a reply to:
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Replies to this message:
 Message 18 by peter borger, posted 01-11-2003 6:41 AM PaulK has replied
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