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The Sound of Circular Reasoning Exploding

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Alternate Title: Of Mice and Men and Evolutionary Dogma

Explosion
“There has been a circular argument that if it’s conserved it has activity.” Edward Rubin, PhD, Senior Scientist, Genomics Division Director, Lawrence Berkeley National Laboratory

Recent experiments cause a central tenet of NDE to miss the prediction. Large swaths of junk DNA (non-coding, no known function) were found to be highly conserved between mice and men. A central tenet of NDE is that unexpressed (unused) genomic information is subject to relatively rapid corruption from chance mutations. If it’s unused it won’t do any harm if it mutates into oblivion. If it’s unused long enough it gets peppered with mutations into random oblivion. If mice and men had a common ancestor many millions of years ago and they still have highly conserved DNA in common, the story follows that all the conserved DNA must have an important survival value.

A good experiment to figure out what unknown purpose the non-coding conserved pieces are doing would be to cut them out of the mouse genome and see what kind of damage it does to the mouse. So it was done. Big pieces of junk DNA with a thousand highly conserved regions common between mice and men was chopped out of the mouse. In amazement the mouse was as healthy as a horse (so to speak). The amazed researchers were in such a state because they were confident NDE predicted some kind of survival critical function and none was found.

This is a good avenue for positive ID research. If the function of any of those regions were preserved because they could be of important use in the future… well that would pretty much blow a hole in the good ship NDE the size of the one that sunk the Titanic. Maybe not that big, but it would be taking on water – natural selection can’t plan for the future. Planning for the future with genomic information is the central tenet of ID front loading hypothesis. Lack of any known means of conserving non-critical genetic information is the major objection lobbed at the front loading hypothesis. Evidently there is a means after all.

Life goes on without ‘vital’ DNA

16:30 03 June 2004
Exclusive from New Scientist Print Edition.
Sylvia Pagán Westphal, Boston

To find out the function of some of these highly conserved non-protein-coding regions in mammals, Edward Rubin’s team at the Lawrence Berkeley National Laboratory in California deleted two huge regions of junk DNA from mice containing nearly 1000 highly conserved sequences shared between human and mice.

One of the chunks was 1.6 million DNA bases long, the other one was over 800,000 bases long. The researchers expected the mice to exhibit various problems as a result of the deletions.

Yet the mice were virtually indistinguishable from normal mice in every characteristic they measured, including growth, metabolic functions, lifespan and overall development. “We were quite amazed,” says Rubin, who presented the findings at a recent meeting of the Cold Spring Harbor Laboratory in New York.

He thinks it is pretty clear that these sequences have no major role in growth and development. “There has been a circular argument that if it’s conserved it has activity.”

Use the link above for the full article.

Comments
In regards to ultraconserved sequences, the Nature article makes reference to two previous studies that could not find a function for ultraconserved sequences conserved between human and fish. Those two studies tested in vivo a total of 36 ultraconserved non-coding sequences and did not find function in 9 of them, or 25% of the ultraconserved sequences. That is really something.Jehu
December 8, 2006
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DaveScot, very interesting. The world sure looks brighter thru the eyes of engineers.mike1962
December 8, 2006
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mike re comment 65 Or perhaps a much bigger library was there in the beginning and as phylogeny unfolded according to a PLAN the plans were reduced so that the radiation terminated in organisms with little potential for further diversification. Or maybe in the vast number of living things not sequenced, salamanders (for instance) with a genomes many times the size of mice and men might have all the plans in them for all the major taxonomic groups that followed them, with genome size being reduced as potential for further diversification was reduced. Maybe those are living repositories. Gene sequencing is still so expensive no one I've read has sequenced a genome with an enigmatic c-value. Is evolution still happening today beyond the generation of closely related species and sub-species? Nobody knows. Evolution works too slowly to confirm that. DaveScot
December 8, 2006
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PaV, there is bunches of evolutinary biology that is not challenged by these findings. Evo-Devo, particularly is not a very RM+NS bound topic. There is nothing about these findings that challenges common descent. These findings only address one core issue -- the role of random mutation and natural selection in evolution. The problem with this core issue is that the only alternative even close to the table is, well, telic. DaveScot, back in post #47, you suggested the possibility of "horizontal DNA flow" explaining these findings. If this were so, then the "preserved" data would not present the phylogenic tree. This could be checked easily enough. If in these regions, the chimp and the human are more highly preserved than the mouse and human, (throw in a couple of other test points, a dog maybe, for good measure) and this possibility would be ruled out.bFast
December 8, 2006
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Lurker: As I posted earlier, I think that the (no longer Darwinists) evolutionists have moved onto "evo-devo" (Allen MacNeil), and will probably say (as did MacNeil) that the trick is in how all of this genetic stuff "develops" over time and how they need a theory of developmental biology. The next step is to simply say that Darwin talked about the importance of "embryology", and that's what "evo-devo" is all about anyways. And they'll simply go on their merry way........PaV
December 8, 2006
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Lurker, cut the defeatest attitude, we've got 'em tight with this one. Function must be found or preservation happens dispite no natural selection. That's all. Their best response to this one is to shut up 'an hope it goes away.bFast
December 8, 2006
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Just as NDE theory has morphed to account for all situations - evolution is gradual, except when it's rapid or static - I suspect the theory will just morph again without ever admitting defeat. Maybe they'll call it the "New and Improved NDE Theory (now with twice the dogma)", or perhaps "NDE Theory v12.0".Lurker
December 8, 2006
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geomor Point taken on ultra-conserved. I note Rubin said none were ultra-conserved. Is there a standard or consensus definition of what % identity is "ultra-conserved". I did a quick look and found as low as 87% called ultra-conserved. The CNGs deleted by Rubin were noted as at least 70% identity in all of them but a figure for what qualifies as ultra-conservative wasn't specified. Some definitions of ultra-conserved are 99%. What cutoff did Rubin use? Rubin refers to Berejano for this and that's a bottom cutoff of 95% for "ultra-conserved". The graphs in the nature report of the % matchup have very many of the discrete sequences apparently reaching 90% or more but none quite touching the 95% match. So it appears that "ultra-conserved" depends on who you ask. Clearly quite a few sequences Rubin deleted borders on even the stricter definitions of ultra-conserved. If it was only one or even ten of the more highly conserved sequences one might only puzzle over it and not be really surprised. When it's hundreds of very highly conserved bits plus more hundreds at genomic-normal conservation (70%) it's startling in the extreme. Rubin was amazed as well he should have been.DaveScot
December 8, 2006
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...and if they haven’t been productive you’re going to be demoted to lurker status. I resemble that remark. ;) [moderator] smartass :razz: Lurker
December 8, 2006
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"If mice and men had a common ancestor many millions of years ago and they still have highly conserved DNA in common, the story follows that all the conserved DNA must have an important survival value." Or perhaps (gasp) common descend is a crock, and some designer(s) came up with all the body plans, and shared various components from a "library", and the "junk" just happened to be in the library as filler, etc. Think OOP. Boy would I love to toy with that library. Seems like it would be fun populating a planet with variouos lifeforms that interact. Hmm, I wonder if the "angels" (read: extraterrestial brainiacs) did that on this planet? Seems I read in the Talmud that this is exactly what happened. Hmm.mike1962
December 8, 2006
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No wonder Modern Evo Synthesis is being superceeded. Hmmm, along with Vole info posted here before(by Gil?)... http://www.medicalnewstoday.com/medicalnews.php?newsid=51906 This is turning into a conspiracy against science! Monthy Python was right all along, our world was build by mice!Michaels7
December 8, 2006
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DaveScot, they're realin' and a wrigglin' -- or at least they should be.bFast
December 8, 2006
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geomor NDE does not imply it Natural selection sure implies the more important the sequence the better it be conserved. The nonfunctionality of these sequences has not been proven, and NDE’s prediction very bluntly remains that they are functional, despite the evident fact that they are not essential. You bet the prediction is blunt. I fail to see why in the first paragraph you said NDE doesn't imply this. "Functional" is understated. Natural selection predicts the more functional the better preserved. The preservation of the mice/men regions is exceedingly high. By every measure natural selection predicts mutations in these regions to be grossly intolerable. Rubin's amazement I'm sure wasn't exagerated or unjustified. A correspondingly vital function is indicated. So far no one has found it. This is a profound issue to resolve. Well, we are still sequencing genomes just to identify all the conserved sequence in mammalian genomes, let alone track down what every last bit does. Mouse and human genomes are completely sequenced. I recently did a light survey of genomic analysis software to see what it costs to get into the business of data mining the genome bank. It ain't much. There doesn't seem to be any lack of it that can compare a mouse/man genome to isolate highly conserved sequences, eliminate them from known non-junk DNA, and get the distance from other known functional DNA. This was described as being in a genetic desert of junk DNA. IIRC one swath was a million base pairs. It doesn't seem to me with resources like BLAST running in distributed processing server farms and the software free to download (much of it open source) there's any problem with finding conserved sequences. After all, Rubin found a thousand highly conserved sequences with no known function this way and others have already surveyed at least a dozen mammals, fish, drosophila, to see the extent of it. IIRC there was fish/mammal conservation but no drosophila/mammal conservation. I'd say this deserves a database of its own like the c-value enigma and of course the more genomes surveyed for mysteriously conserved junk DNA the better we should be able to get a handle on its purpose. I wrote elsewhere about this (could've sworn it was here though) the cost of sequencing 3 billion base pairs with a tolerable degree of accuracy for data mining is down close to $100,000 as reported in a recent article in Scientific American. The Archon X Prize goes to whoever gets it down to $10,000 and the U.S. gov't is funding a program to get a human genome down to $1000. That's about as much as an MRI scan. In short, affordable to a vast number of people as a diagnostic tool for medicine. An effort I fully support. DaveScot
December 8, 2006
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Sabre, that's how I see it. Chunkdz, if the thing is found in frogs, we're dealing with a mear 500 million years (250M ancestor to frog, 250M ancestor to mouse.) But 140m, 500m in this case it doesn't make a hair of a difference -- 20m might help. Douglas chimes in -- how 'bout 6000!bFast
December 8, 2006
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bFast,
So these sequences are even more conserved between mice and men than even protein coding genes.
It appears to me that they have a different code than the protein expressing "central dogma" genes, this code does not have the alternative spellings that are acceptable in the "central dogma." I should also point out that function in gene regulation has been demonstrated for many of these CNG's.Jehu
December 8, 2006
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bfast, For the record, the article defines ultra conserved as being conserved across mamamals and fish. However there were some large sequencs, conserved amongst birds, mammals, and frogs with 90% identity. From the article:
From the MU19 desert we picked five human-mouse conserved elements representing the most conserved sequences between these species (more than 180 bp, 90% identity ) for the in vivo assay. The ten elements chosen from desert MMU3 ( more than 400 bp, 90% identity ) included all five sequences that are conserved across humans, rodents, chicken and frog , and five that are conserved across humans, rodents and chicken only.
It should be noted that from those 15 sequences they found a small function in one of the sequences. I have mentioned that function twice before in this thread already and suffice it to say there is no indication it provides selective benefit.Jehu
December 8, 2006
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The paper indicates that some of the conserved sequences were conserved in frog genomes as well. Does this mean that we are talking about hundreds of millions of years of conservation, not just 70-90 million years? I'd like to see knockout experiments on frogs using the relevant sequences.chunkdz
December 8, 2006
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DaveScot, perhaps the scientists in question suspect the answer such additional research would yield/confirm, and don't want to face it. Many people who suspect thier cherished spouses are unfaithful will go to great lengths to avoid knowing for certain. So too might it be for a cherished belief.sabre
December 8, 2006
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DaveScot, let me keep this discussion painfully honest, after all we've got 'em this time, and we don't need to bungle it. The original publication, link in post #4 says:
Together, the two selected regions contain 1,243 human–mouse conserved non-coding elements (more than 100 base pairs (bp), 70% identity), also similar to genome averages, whereas no ultraconserved elements9 or sequences conserved to fish (more than 100 bp, 70% identity) are present.
If 70% conserved is the average, I'm still very interested to know how conserved the most conserved region is.bFast
December 8, 2006
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The deleted sequences were not ultraconserved. They explicitly avoided deleting ultraconserved sequences. The deleted sequences fall into a category of conserved sequences less than "ultra" :-)GeoMor
December 8, 2006
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darth To immediatley conclude that this is prove for genetic planning for the future is premature. that does not help convicing people of the idea of ID. I said nothing about proof. That's a straw man. I explicitely suggested that this would be a good line of research for ID to undertake. I'm going to review the productivity of your previous comments here and if they haven't been productive you're going to be demoted to lurker status. Update: Darth is a new commenter who joined just yesterday. I've added him to the moderation list for now. I expect better than straw men in critical commentary, Darth. Don't do it again. DaveScot
December 8, 2006
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sparc What you say is obvious and any competent researchers would attempt to simulate a natural pathogenic environment to the modified mice. It's been over two years. No explanations for function in the missing DNA have been confirmed. How very interesting. Keep in mind these sequences aren't just conserved. They're described as ULTRA-conserved. Moreso than protein coding genes. Now it might be that protein coding genes are just more resilient in tolerating sequence variation without compromising their function but still that's just a hypothetical and the true nature of all this remains a mystery. In response to your description of a gene knockout where a mouse lived happily ever after unless exposed to certain pathogens I'd respond by saying this knockout wasn't one isolated gene but over a million base pairs encompassing a thousand discrete conserved sequences. It's hardly comparable to a single coding gene knockout in that regard. Furthermore, I read in some of the other articles that were dug up is that a good fraction of these conserved sequences are present in fish and at least twelve other mammals. What pathogens are common between fish, mice, and men? I'm very surprised that a lot more research into this hasn't been undertaken in the intervening two+ years. DaveScot
December 8, 2006
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To be fair, the knockout DNA might be part of, say, a genetic repair mechanism such that the result of its deletion would be cumulative over many generations of mice guaranteeing that the variant line absent the DNA would be driven to extinction. The repair mechanism would of course be shared by mice and men through common ancestry. One would hope that the variant line has been preserved in the lab so that it can be observed over the long haul for the emergence of serious problems. I should think that was almost certainly the case as it's so obvious. Given there's been over two years for the line to breed and no subsequent reports of ailments in the lineage there's probably nothing definitive in that regard so far. There's also an uncontrolled variable in such a line of inquiry - namely inbreeding. Because the deletion was only performed on a few individuals to make them homozygous for the deletion the known detrimental effects of inbreeding can be expected to show up. Distinguising between inbreeding ailments and deletion ailments could be very problematic. DaveScot
December 8, 2006
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Patrick I thought about instinctual behavior before I wrote the article. I ran into three problems seemingly without resolution under the natural selection paradigm. 1) what instincts are shared between mice and men 2) which of those common instincts are so important to survival that they'd be ultra-conserved more than coding proteins? The suckling instinct came to mind. 3) Why did the mice not show an adverse effects on losing instincts which must be so important? A baby mouse not able to suckle would die and the loss of the instinct would be easily noted to anyone closely observing the knockout mice.DaveScot
December 8, 2006
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bfast Great work in digging up more dirt! This should have been a proverbial shot heard 'round the world two years ago and instead the implication for natural selection seems to have been by and large quietly disregarded. Mayhap anyone with a vested interest is worried about being Sternberged for being too candid about the implication for natural selection. If previous patterns of response are repeated a chance worshipper will alert Dr. Rubin he's being "quote-mined by intelligent design creationists in support of their pseudo-science" :razz: and what does he have to say in response to them.DaveScot
December 8, 2006
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troutmac The win for ID is that there's a mechanism for ultra-conservation of DNA with no immediate survival value. The basic premise underlying natural selection is that DNA with no immediate selection value is subject to rapid random mutation and DNA with immediate survival value will be conserved (i.e. mutations in it kill or cripple the host so the mutation doesn't propagate in the population). This is a huge failed prediction of natural selection. The front loading hypothesis of ID predicted a mechanism of conserving unexpressed genomic information. I've been blogging about that prediction for over a year. This is vindication most sweet.DaveScot
December 8, 2006
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bfast Maybe it's supposed to be one of those trade secret things. Gould said it was a trade secret of paleontology that the fossil record doesn't support support gradualism. Maybe there's now a trade secret in genomics that conserved sequences aren't necessarily important to immediate survival. By the way, I read in another article here http://www.panspermia.org/nongenseq.htm
The faithfulness of conservation which this study observed in the CNGs is unprecedented. The most highly conserved ones have a nucleotide substitution rate, across the studied mammals, that is less than half that of protein-coding genes.
So these sequences are even more conserved between mice and men than even protein coding genes. Trade secret indeed.DaveScot
December 8, 2006
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Sal I kept going over possible ways this could be redundancy and it just didn't play out. The patter goes that these bits are SO important that in case they get corrupted a backup set takes over. So what's protecting the backup set from corruption? We keep returning to the unavoidable fact that these highly conserved sequences were deleted and nothing bad happened. A redundancy mechanism would have to engender some kind of corrective action when a backup is corrupted - like killing the organism. It just doesn't add up. The only thing I've been able to think of so far that fits the NDE model is horizontal DNA flow. Some very recent event, a retrovirus perhaps, caused these sequences to be inserted in both mouse & human genomes. But other researchers have discovered more or less the same sequences in a dozen different mammals. Whatever the answer, it's going to be interesting and at this point it sure looks like a big KABOOM for the circular reasoning "if DNA is important for survival it's conserved and if DNA is conserved it's important for survival".DaveScot
December 8, 2006
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GeoMor:
No one is running from the principle that “conservation implies function” because it has proven so scientifically fruitful in understanding how our genomes operate and evolve.
As I posted on another thread, I think it's possible that "evolutionists" are running away from it. Prof. Allan MacNeil, for example, has said something to the effect: "The Modern Synthesis is dead. Long live evo-devo." Conserved sequence=essential function is certainly part of the Modern Synthesis. It seems that maybe some scientists see what I saw in reading the article two years ago: Darwinism (Modern Synthesis) is dead. Only the "obits" haven't carried the news. Not yet, anyway.PaV
December 8, 2006
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Me: “Obviously, since Evolution is true, the experiment does not cast doubt on Evolution, but merely shows that mice and men are very closely related.” bFast: "You may read back in post 2 that I mention that these findings are consistent with a young earth. I’m still an old earther on acounta all that other evidence flyin’ in from everywhere." I saw where you mentioned that about a young Earth. (We'll convert you, yet, so be ready.) And, my post was more directed at those who subscribe to Neo-Darwinian Theory. Although, now that you mention it, I thought I had noticed some buzzing noises - I guess I assumed they were mosquitos. ;)Douglas
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