Uncommon Descent Serving The Intelligent Design Community

Ultra-conserved DNA with no evident immediate purpose


Edward Rubin again finds hard evidence supporting a front loaded evolution. Front loading is a design engineering term generally used to describe design elements inserted for possible use in the future (contingency) as opposed to immediate use. The mechanism of random mutation and natural selection is incapable of contingency planning. RM+NS can build based on experience but can’t build based on an abstract future. It is reactive not proactive. The front loading hypothesis in essence says the complex specified information necessary to construct the more complex machinery of life has been around since life appeared on the earth but much of it was preserved for expression in the far distant future. Natural selection cannot preserve unexpressed information for long against the onslaught of random mutation. What’s unimportant for survival mutates into random junk or is deleted altogether. Thereby the RM+NS theory predicts that any DNA sequences that are preserved, mostly or entirely unchanged, for tens and hundreds of millions of years must be very important for survival and reproduction. The most serious objection to evolution (phylogenesis) being a front loaded process is that there is no known mechanism that can preserve unexpressed DNA for long periods of time. A front loaded phylogeny can be compared to ontogeny (the process of a single organism going from egg to adult) except that phylogeny takes many millions of years for the diversification of a single cell into many specialized cells and organisms whereas individual organisms go from one cell to many very specialized cells and organs in a matter of days or weeks. Phylogenesis is no more dependent on random chance for what it produced than ontogeny is dependent on chance – both have a predetermined course of action.

Rubin and his research have turned up compelling evidence that there is some unknown mechanism (something other than natural selection) which is working to preserve genomic information for geologic periods of time. We blogged Rubin’s last experiment where millions of highly conserved (75%-95% sequence similarity) DNA base pairs were deleted from a mouse with no observed deleterious effect on the genetically modified progeny. Below is the abstract and author summary from his latest paper in this area of research where four ultraconserved (95% – 100% sequence similarity) DNA regions were deleted. Click the link below to read the whole paper. My emphasis added in bold where the authors express surprise. These results are no surprise to front loading pundits, that’s for sure.

Deletion of Ultraconserved Elements Yields Viable Mice

Nadav Ahituv, Yiwen Zhu, Axel Visel, Amy Holt, Veena Afzal, Len A. Pennacchio, Edward M. Rubin

Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States Department of Energy Joint Genome Institute, Walnut Creek, California

PLoS Biology: September 4, 2007

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the necessities of these elements in vivo, we removed four noncoding ultraconserved elements (ranging in length from 222 to 731 base pairs) from the mouse genome. To maximize the likelihood of observing a phenotype, we chose to delete elements that function as enhancers in a mouse transgenic assay and that are near genes that exhibit marked phenotypes both when completely inactivated in the mouse and when their expression is altered due to other genomic modifications. Remarkably, all four resulting lines of mice lacking these ultraconserved elements were viable and fertile, and failed to reveal any critical abnormalities when assayed for a variety of phenotypes including growth, longevity, pathology, and metabolism. In addition, more targeted screens, informed by the abnormalities observed in mice in which genes in proximity to the investigated elements had been altered, also failed to reveal notable abnormalities. These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability.

Author Summary

It is widely believed that the most evolutionarily conserved DNA sequences in the human genome have been preserved because of their functional importance and that their removal would thus have a devastating effect on the organism. To ascertain this we removed from the mouse genome four ultraconserved elements—sequences of 200 base pairs or longer that are 100% identical among human, mouse, and rat. To our surprise, we found that the mice lacking these elements are viable, fertile, and show no apparent abnormalities. This completely unexpected finding indicates that extreme levels of DNA sequence conservation are not necessarily indicative of an indispensable functional nature.

HT to Jehu for recognizing the importance of the paper for front loading and bringing it to my attention.

Can anyone explain me following stuff! Do I understand correctly that with all this front-loading in Anemons and Mice we have parts of DNA which are not functional in Mouse but identical parts of DNA in human ARE functional? Otherwise I don't see where is front-loading, if the part of DNA is dead for all the species? And if it is NOT dead (we don't know function) then how we know that there is no function in Anemone for the code? What did I missed? Shazard
I have a couple questions. If the sequences are ultra conserved for millions of years, then there are two possible reasons for this. 1. The sequences are highly functional or else they would mutate away so this implies even slight mutations would make the organism unlikely to survive. 2. There is some mechanism within the genome which is unknown that is preserving these sequences intact. This unknown function is also not understood as to why it would do it as well as how it would do it. Are there any other reasons for a sequence to be conserved? What are the implications of each scenario? I understand that the sequences have been knocked out and the offsprings have survived and reproduced. If this is so then why wouldn't a mutated version of the sequence also allow the offspring to survive? The survival implies that the absence of the sequence seems to be more desirable than the mutated version. Would it now make sense to mutate the sequences artificially instead of knocking them out to see how this affects survival? jerry
If ID doesn’t do original research, what was going on at the infomatics lab that was shut down by Baylor?
Oh, yeah. There's that. russ
If ID doesn't do original research, what was going on at the infomatics lab that was shut down by Baylor? Jehu
This is an excellent opportunity to apply the techniques of ID reserach. Dr. Dembsky should use ID theory to predict or imply functions from an ID point of view. that would finally satisfy the ID critics who claim that ID does not do original research. IrrDan
Actually we don't know if the sequences are highly functional or not in humans. Jehu
It would be fascinating if some organism with identical or highly similar sequences were shown to be actually using the sequence. So while the sequence is dormant yet highly preserved in mouse and human, what if it is critical to the function of a whale? That would be an interesting finding for front loading. Jehu
The theme that continues to recur is that NDE is surprised by new discoveries (rather than new discoveries that confirm NDE predictions). These same discoveries provide an opportunity for ID predictions to be tested. Would it make sense to compile ID predictions some place within UD? Some of these include (as stated above): redundancy and adaptability. The ultraconserved sequences might also demonstrate that the purpose of life extends beyond the NDE purpose of survival of the next generation. dgw
Dave Scot, As well as providing a compelling and crushing evidence against natural selection of the evolutionary scenario, Would not this also ,at least, hint at problems with the similarity of DNA being used as proof of common descent even in a ID scenario? I do not know much about the ID argument for common descent so I would appreciate your views on the implications for it, if you don't mind. bornagain77
Also I like this quote from your link DLH: The literature I cited is clear about it: genetic redundancy provides an organism the robustness to withstand mutations. And there is no association with gene duplications and redundant genes do not mutate faster than essential genes. Your teacher should start by seriously reading my references. This is a definite hard slap in the face to RM. It appears the first clear reading of the evidence points to a design that would negate the effects of mutations....LOL What are evolutionists going to possibly say now? LOL ..They are really going to have to dig into their fantasy bin for some lies to explain this away! bornagain77
I Think Mullerpr asked a very interesting question. Did the researchers check any viable offspring to see if the DNA repaired itself? bornagain77
Sorry, spelling: independant->independent. Apollos
I believe (take it on faith) that what is now commonly thought to be "evolution" will turn out to be merely a mechanism that functions to keep the design of various organisms on track, rather than any sort of independant creative force. In the RM+NS paradigm, I see RM as basically the destructive element, where NS combined with DNA redundancy and other mechanisms work to keep the original design intact enough to propagate. I think of this as RM versus NS+Design, where NS+Design work to keep organisms alive against the assaults of RM. I fully accept that this could prove to be nothing more than my own little fantasy. However, if ultra-conserved DNA is indeed redundant, we should expect to see deleterious results in further generations of the progeny with the deleted elements, as RM works to do its "magic." I wonder if there are ultra-conserved sequences in bacteria that could be knocked out. This way it could be shown fairly rapidly whether strains with the removed sequences suffered deleterious effects in subsequent generations, versus strains with the conserved regions intact. Apollos
As an engineer, I frequently employ redundancy in my designs. If ID infers DNA is an example of design, gene-redundancy is an obvious outcome from this inference, IMO (a prediction, if you will. I wonder how long before we can safely say redundancy is a confirmed prediction of ID). JJS P.Eng.
This is very interesting. What I would like to know is if the researchers checked the viable offspring's DNA to see if that removed unnecessary sequence might have been repaired in the offspring? Hence the viability. I am not a biologist by a long shot, but I think this should be a logical part of this experiment. Since I did not read the complete article my question might be in ignorance. mullerpr

Such findings may also reflect genetic redundancy - another design feature to give more robustness.

e.g., See:
Genetic Redundancy: The Ultimate Evidence of the Design of Life

by Peter Borger

Abstract: The fundamental premise of the intelligent design concept is that biological systems are the result of intelligent design. Question is however, how the design of such systems can be unequivocally recognized. It has been argued that the irreducible complexity of biological systems can only be explained invoking intelligence and as such it is often presented as evidence of intelligent design. The Darwinians interpretation of irreducible complex systems and their apparent design is that they are the ultimate accumulated result of the natural selection of slightly advantageous traits. Straightforward unambiguous evidence for the design of biological systems should come from observed biological systems that cannot be the result of natural selection. If we would find a biological system to exist for which we must assume neutral selection, then we would not only have the evidence for intelligent design, but the system would also qualify as a falsifier of Darwinian Theory. Over the past two decades scientists have observed the peculiar biological phenomenon of genetic redundancy, which pertains to genes or genetic systems that seem to have no obvious function. Indeed, genetic redundancy is now defined as the situation in which the disruption of a gene is selective neutral. Genetic redundancy is the resultant of cooperating scale free genetic networks that provide robustness to organisms. One of the biggest surprises of modern biology genetic redundancy terminates Darwin’s era of natural selection. Full article here

Does this now mean evolutionists will start to question the way they look at the DNA as a product of evolution? I don't think so. As far as ID goes though this evidence should give us further evidence to abandon any Neo-Darwinism links we may have and to start asking "outside the box" questions to deduce and answer the exact amount of complexity we are actually dealing with in DNA! bornagain77

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