Pseudogenes do function (Introduction)
by David Turell 
, Saturday, October 20, 2012, 01:08 (4395 days ago)
In cancers according to a recent paper:-http://stke.sciencemag.org/cgi/content/abstract/5/242/re5-The conclusion:-"The function of the great fraction of the human genome (98%) composed of sequences that do not encode proteins remains a mystery. Pseudogenes are technically part of this fraction, and the examples described here clearly demonstrate that they perform a broad and multifaceted spectrum of activities in human cancer. Therefore, the name pseudogenes, which underlies their close sequence similarity with parental counter-parts, should not imply a negative connotation. They might be "pseudo" genes because they do not encode a protein or because they encode a protein that does not function in the same way as that encoded by their cognate genes. Nonetheless, they are functionally disabled but can perform different functions than their parental gene counterparts."
Encode supported
by David Turell , Thursday, November 01, 2012, 14:24 (4382 days ago) @ David Turell
Research is turning up more evidence of junk DNA function:- "We are delighted to see that there is one more function for long non-coding RNAs," says Piero Carninci, Team Leader at RIKEN OSC. "Since the initial discovery that the majority of the genome produces so many non-coding RNAs, there has been a general skepticism related to the possible function of these RNAs. This is a milestone study identifying a novel class of non-coding RNAs which have a key regulatory function, enhancing protein translation. Additionally, this function is mediated by repetitive elements, so far generally considered the 'junk' fraction of the genome, suggesting that the concept that most of the genome is 'junk' should be revisited. After all, there may be function embedded in any part of the genome, which we do not yet understand."-http://www.sciencedaily.com/releases/2012/10/121016084940.htm
Encode supported
by David Turell , Monday, November 05, 2012, 20:37 (4378 days ago) @ David Turell
Encode data dump shows how large the study was. Note only 147 cell types DNA was used. That means only slightly less than 50% of all cell types were studied. There is lots more to expect.:-http://www.the-scientist.com/?articles.view/articleNo/32983/title/A-Guide-to-the-Epigenome/
Encode rejected
by David Turell , Friday, February 22, 2013, 23:22 (4269 days ago) @ David Turell
A very critical paper has just appeared downplaying the ENCODE claim that 80% of DNA is functional. The meaning of the word functional is debated and twisted in a extraordinary way. My take is that the huge DNA molecule at times has controlling segments which need to be a a certain 3-D realtionship to the gene. The DNA is coiled around histone spools and this arrangement requires modifying elements, various RNAs, to be at a seeming distance when DNA is expressed in a linear fashion, but in fact those elements are close by in the naturally coiled state. -http://gbe.oxfordjournals.org/content/early/2013/02/20/gbe.evt028.full.pdf+html
Encode rejected
DAVID: A very critical paper has just appeared downplaying the ENCODE claim that 80% of DNA is functional. The meaning of the word functional is debated and twisted in a extraordinary way. My take is that the huge DNA molecule at times has controlling segments which need to be a a certain 3-D realtionship to the gene. The DNA is coiled around histone spools and this arrangement requires modifying elements, various RNAs, to be at a seeming distance when DNA is expressed in a linear fashion, but in fact those elements are close by in the naturally coiled state. -http://gbe.oxfordjournals.org/content/early/2013/02/20/gbe.evt028.full.pdf+html-Hardly "downplaying" ... this is a devastating dissection and rejection of the methods and findings of the researchers. For a layman like myself it's impossible to make a judgement, and one needs at least to see a response from the ENCODE researchers themselves. It's not clear to me from your own comments whether you are accusing the critics of twisting the meaning of "functional" or repeating their own accusation that this is what the ENCODE people have done. It's obviously a crucial point, and since you are our resident science expert, I would love to know whether you think the criticisms do or don't sound justified. Again this is not clear to me from your comments.-You have often slated research bodies for the amount of money they waste on useless projects. If the critics are right, this is even worse than useless ... 288 million dollars have been spent on what amounts to falsifying the accounts!
Encode rejected
by David Turell , Saturday, February 23, 2013, 15:38 (4268 days ago) @ dhw
dhw: It's not clear to me from your own comments whether you are accusing the critics of twisting the meaning of "functional" or repeating their own accusation that this is what the ENCODE people have done. -I've chosen to answer this one question of yours as the entire subject is very convoluted. Encode folks are as valid and clear thinking microbiologists as James Shapiro, and just as frightening to committed Darwinists, who are defending the old turf. These are scientific brains at war. The word 'functional' is twisted beyond belief in the meat of the article, and the purpose is to degrade the statement of Encode that 80% of the DNA is 'functional'. What Encode showed is that modifying segments of gene expression are scattered over 80% of the molecule. So far, what is inbetween those segments may be simply spacers for 3-D purposes as I noted, may have no other purpose, or may have some other not yet detected functionality.-A key tenet of Darwinism is that the DNA is so giant because a lot of junk DNA was left behind as evolution progressed in developing this molecule. This article now claims that there is useful junk (!) and true garbage, the first time that term has appeared. Darwin does not explain why the amoeba has a larger DNA than humans and some plants have 15-20% more. DNA has been a giant molecule from the beginning of life. And human DNA is filled with transpositions, repeats, viral segments, and so on. Yet the controls over the code are extremely tight in the copy mechanisms. Is junk, junk or isn't it? That is really not clear as functions are found where originally none was expected to be. That is a key, expectation based on preceding theory. The original thinking about a simple DNA coding process, one gene, one protein produced, is totally out the window. Original Darwin expectations are constantly twisted beyond belief by new discoveries. The complexity complexifies on a weekly basis with every new finding.-What is apparent to me from reading Shapiro's recent book is that the scientists who are nanotechnicians in their study of the nanomachines in cells, may be committed to evolution as a valid process, but raise serious doubts about the nitty-gritty of basic Darwin theory. This is appearing from philosophers of science like Nagel. Darwin's simple, common descent, natural selection and random mutationcan't possibly explain the complexity in the cells. DNA does not fit the template proposed by the evolution theorists prior to these discoveries. -What is obvious to me is simple Darwinism does not work when the new findings are analyzed, and the authors of this article are semantically scrambling to redefine what functionality is, to degrade the conclusions of the Encode group.
Encode rejected
ENCODE claim that 80% of DNA is functional. Their critics attack their methods and their findings. It seems to me, from my position on the layman's fence, that if something is functional, it serves a purpose. If it is not functional, it serves no purpose. If ENCODE have explained what purposes are served by the 80%, there should be no dispute. If they haven't explained the purposes, then the figure is meaningless. But what do I know?-David, thank you for your detailed response. In it, you attack Darwin as if he should have known all about DNA and modern genetics, but of course you are really attacking those neo-Darwinists who are out to prove that evolution dispenses with God. Like many such disputes, this one seems to me pretty superficial. Whether 80% or 10% is useful, what we have is a working mechanism so complex that it defies belief in chance. If there are big bits or little bits left over (as with vestigial structures), are scientists claiming they could have done a better job, and so DNA wasn't designed? Do left-overs lessen complexity? The existence, non-existence or proportions of junk DNA prove nothing either way in the design debate. The question is how functional DNA arose in the first place. -However, you wrote: [Nanotechnicians] "may be committed to evolution as a valid process, but raise serious doubts about the nitty-gritty of basic Darwin theory. [...] Darwin's simple, common descent, natural selection and random mutation cannot possibly explain the complexity in cells." You and I and countless others agree that random mutation and gradualism are major flaws in the theory, but Darwin's great achievement was indeed to establish evolution "as a valid process", and any attack on him needs to be properly differentiated. Common descent is the "nitty-gritty", as against the then common belief in separate creation, and natural selection explains why some organs and organisms survive while others perish. These concepts are not MEANT to explain the complexity of cells. The unresolved problem within his theory is how cells are able to adapt and invent. Darwin almost certainly guessed wrong, but he knew full well how incomplete his picture was: "...when we contemplate every complex structure and instinct as the summing up of many contrivances, each useful to the possessor, nearly in the same way as when we look at any great mechanical invention as the summing up of the labour, the experience, the reason, and even the blunders of numerous workmen; when we thus view each organic being, how far more interesting ... I speak from experience ... will the study of natural history become! A grand and almost untrodden field of inquiry will be opened, on the causes and laws of variation, on correlation of growth, on the effects of use and disuse, on the direct action of external conditions, and so forth. [...] Our classifications will come to be, as far as they can be so made, genealogies; and will then truly give what may be called the plan of creation" (Recapitulation and Conclusion, Origin).-These fields are now indeed being opened up. Interestingly for you, perhaps, he goes on once more to oppose separate creation, and thinks his theory "accords better with what we know of the laws impressed on matter by the Creator." Atheist neo-Darwinists will never quote such statements ... or will say Darwin was appeasing his wife ... but the fact remains that he himself said evolution and religion were compatible, and towards the end of his life he also made it clear that he regarded himself as an agnostic and had never been an atheist. I do wish atheists and theists alike would stop using and abusing Darwin to suit their own purposes.
Encode rejected
by David Turell , Sunday, February 24, 2013, 18:24 (4267 days ago) @ dhw
dhw:These fields are now indeed being opened up. Interestingly for you, perhaps, he [Darwin] goes on once more to oppose separate creation, and thinks his theory "accords better with what we know of the laws impressed on matter by the Creator." Atheist neo-Darwinists will never quote such statements ... or will say Darwin was appeasing his wife ... but the fact remains that he himself said evolution and religion were compatible, and towards the end of his life he also made it clear that he regarded himself as an agnostic and had never been an atheist. I do wish atheists and theists alike would stop using and abusing Darwin to suit their own purposes.-In the preceding entry by Behe, he carefully dissects the Darwin theory as three portions: common descent, natural selection and random mutation. He accepts common descent as very important and and the other two as relatively minor. Natural selection can only act when competition is present and on whatever organism is presented to NS by evolution. He discusses mutations as generally destructive of DNA, and wonders if evolution has reached its pinnacle of development. His discussion of malaria shows that the so-called beneficial changes in hemoglobin to thwart the parasite are really very distrutive to humans with the various anemias that have appeared as a result.The video has poor sound when the introducing lady is at the mike. Behe is quite clear once he adjusts his mike. Behe offers no clue as to how a new species might develop. Darwim also had no clue. -He also discusses Lensky's work with 50,000 generations of E. coli. No new species, some minor modifications. Where is evolution is the question.
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Dhw: You and I and countless others agree that random mutation and gradualism are major flaws in the theory. [...] Common descent is the "nitty-gritty", as against the then common belief in separate creation, and natural selection explains why some organs and organisms survive while others perish. These concepts are not MEANT to explain the complexity of cells. The unresolved problem within his theory is how cells are able to adapt and invent. Darwin almost certainly guessed wrong [i.e. random mutations], but he knew full well how incomplete his picture was.-I then quoted Darwin's forecast that "an almost untrodden field of inquiry will be opened, on the causes and laws of variation" etc. DAVID: In the preceding entry by Behe, he carefully dissects the Darwin theory as three portions: common descent, natural selection and random mutation. He accepts common descent as very important and the other two as relatively minor. Natural selection can only act when competition is present and on whatever organism is presented to NS by evolution. He discusses mutations as generally destructive of DNA, and wonders if evolution has reached its pinnacle of development.-Thank you for this summary, which in effect is saying exactly the same as my own post, other than the speculation that evolution may have reached its pinnacle. DAVID: Behe offers no clue as to how a new species might develop. Darwin also had no clue.-That is why the title of Darwin's masterpiece is so misleading. He himself spends a long time bemoaning the fact that nobody actually knows how to define species! In the meantime, you and I have gone one better than both Darwin and Behe, as we have agreed on the likeliest explanation ... namely, that the genome is possessed of some form of intelligence which enables organisms to adapt and invent. Darwin's book sets out to prove that evolution happened. In relation to the eye, he wrote: "How a nerve comes to be sensitive to light, hardly concerns us more than how life itself originated." In the context of how evolution works, we might say: "How the genome comes to be intelligent hardly concerns us more than how life itself originated." In the context of whether God exists or not, these two questions of "how" become all-important, but that is a matter of focus, and one can hardly blame Darwin for expounding his theory of evolution instead of discussing whether God exists or not. I do not have a first edition of Origin to compare mine with, but for the record, later editions mention many times that all this was the work of "the Creator", although I must repeat (ad nauseam!) that Darwin regarded himself as an agnostic.
Encode rejected
by David Turell , Tuesday, February 26, 2013, 02:10 (4266 days ago) @ dhw
Another take on encode, rejecting it and quoting the article I presented:-http://blogs.scientificamerican.com/the-curious-wavefunction/2013/02/21/encode-applemaps-and-function-why-definitions-matter/?WT_mc_id=SA_CAT_EVO_20130225
Encode supported?
by David Turell , Friday, April 12, 2013, 22:27 (4220 days ago) @ David Turell
A new discussion, even handed about encode.-"ENCODE's leaders have painted a picture of the human genome in which most of the parts are efficiently put to use, and that's not the right way to see it, critics say. "It's important to distinguish between: Is the human genome a perfect machine? The best of all possible genomes? Or is it a mess?" says Sean Eddy, a genomics researcher at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Virginia who helped plan ENCODE. "What we know about genomes is far more compatible with its being a glorious mess." By "mess," Eddy is referring to conclusions from mathematical models of evolution, which suggest at least 85 to 90 percent of the genome must not be critical to human health, even if it is chemically active. Part of the reasoning is that so many random mutations arise over time, humans would have died off if most of the genome were so critical that mutating it would have a major effect on health. On the other hand, Stamatoyannopoulos and Schadt say that those models, some of which rely on simple equations that have been around since the 1960s, could have gotten their numbers wrong. That's possible, Eddy says, but scientists should develop better arguments against the models before discounting them."-http://www.scientificamerican.com/article.cfm?id=friction-over-function-encode&page=2
Encode discussion
by David Turell , Saturday, April 13, 2013, 20:11 (4219 days ago) @ David Turell
Another point of view re' Encode. How valid are the findings? How much is junk? Should we drop the phrase?-http://online.wsj.com/article/SB10001424127887323550604578410794018082244.html-"The first row concerns the phrase "junk DNA." Coined in 1972 by the geneticist Susumu Ohno, it is an attempt to explain why vast stretches of animal genomes, far more in some species than in others, seem to serve no purpose. Genes of all kinds and their control sequences make up maybe 9% of the human genome at the very most. The rest may be nonfunctional "junk," mainly there because it is good at getting itself duplicated. Yet the phrase has always caused a surprising amount of offense. Reports of the discrediting of junk-DNA theory have been frequent." "Late last year, a huge team of scientists running a consortium called Encode published an analysis of the human genome that they said showed some kind of activity in 80% of the genome. They later conceded that perhaps 20% is actually functional, yet insisted the phrase "junk DNA" could now be "totally expunged from the lexicon." "According to Dan Graur of the University of Houston and his colleagues, even this is a wild overestimate—not least because it uses a "causal role" definition of function that is all wrong, as if you were to describe among the heart's functions adding 10.5 ounces to the weight of the body, along with pumping blood. After a few exchanges, the Encode team leader Ewan Birney conceded that in hindsight, the team overstated its conclusions. But he added that whatever the interpretation, the Encode data are sound." "Are they? Here's where the junk-DNA row meets the other conflagration in molecular biology. All the Encode data were derived from cancer-cell lines. To describe human cancer cells as having the human genome looks increasingly unwise. Most cancer cells have extra chromosomes, fragmented and rearranged DNA and unusual patterns of gene activity."-"Comment: "The supposed junk may be "functional" simply by virtue of its space-filling role."-The 3-D approach to DNA is right on. It is coiled around spools of histone and parts of the gene are then in contact with modifiers elsewhere, which would not be the case if the DNA were linear.
Encode supported?
by David Turell , Monday, August 05, 2013, 15:48 (4105 days ago) @ David Turell
Another article supporting Encode:-http://www.thehugojournal.com/content/7/1/2
Encode supported?
by David Turell , Thursday, August 15, 2013, 18:54 (4095 days ago) @ David Turell
More from this article:-"In essence, the argument posits that the presence of non-protein-coding or so-called 'junk DNA' that comprises >90% of the human genome is evidence for the accumulation of evolutionary debris by blind Darwinian evolution, and argues against intelligent design, as an intelligent designer would presumably not fill the human genetic instruction set with meaningless information (Dawkins 1986; Collins 2006). This argument is threatened in the face of growing functional indices of noncoding regions of the genome, with the latter reciprocally used in support of the notion of intelligent design and to challenge the conception that natural selection accounts for the existence of complex organisms (Behe 2003; Wells 2011). "Conclusions It is our position that these arguments are misguided. Indeed, we have refuted the specific claims that most of the observed transcription across the human genome is random (Clark et al. 2011; Mercer et al. 2012) and put forward the case over many years that the appearance of a vast layer of RNA-based epigenetic regulation was a necessary prerequisite to the emergence of developmentally and cognitively advanced organisms (Mattick 1994; Mattick and Gagen 2001; Mattick 2004; Amaral et al. 2008; Mattick 2009a, 2011). This case is, moreover, entirely consistent with the broad tenets of evolution by natural selection, although it may not be easily reconcilable with current population theory and current ideas of evolutionary neutrality. In any case, that our understanding of the remarkably complex processes underlying the molecular evolution of life, including the likely evolution of evolvability (Mattick 2009c), is incomplete should not be surprising. With the emergence of transformative technologies, such as massively parallel sequencing, which provide tools to view the inner molecular workings of the genome that were inconceivable less than a decade ago, it is as important as ever that we as scientists remain open to observations that challenge even the most fundamental paradigms that exist within biology today."-http://www.thehugojournal.com/content/pdf/1877-6566-7-2.pdf