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Breaking: A “junk DNA” jumping gene is critical for embryo cell development

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Not junk: 'Jumping gene' is critical for early embryo
Two-cell mouse embryo stained for LINE1 RNA (magenta/Ramalho-Santos lab, UCSF

This was discovered by someone who was skeptical of the idea that our geomes are largely useless junk. From Nicholas Weiler at Phys.Org:

A so-called “jumping gene” that researchers long considered either genetic junk or a pernicious parasite is actually a critical regulator of the first stages of embryonic development, according to a new study in mice led by UC San Francisco scientists and published June 21, 2018 in Cell.

Only about 1 percent of the human genome encodes proteins, and researchers have long debated what the other 99 percent is good for. Many of these non–protein coding regions are known to contain important regulatory elements that orchestrate gene activity, but others are thought to be evolutionary garbage that is just too much trouble for the genome to clean up.

For example, fully half of our DNA is made up of “transposable elements,” or “transposons,” virus-like genetic material that has the special ability of duplicating and reinserting itself in different locations in the genome, which has led researchers to dub them genetic parasites. Over the course of evolution, some transposons have left hundreds or thousands of copies of themselves scattered across the genome. While most of these stowaways are thought to be inert and inactive, others create havoc by altering or disrupting cells’ normal genetic programming and have been associated with diseases such as certain forms of cancer.

Now UCSF scientists have revealed that, far from being a freeloader or parasite, the most common transposon, called LINE1, which accounts for fully 24 percent of the human genome, is actually necessary for embryos to develop past the two-cell stage. More.

“evolutionary garbage that is just too much trouble for the genome to clean up”?  Yes, because Darwinism has predicted that.

Hat tip: PaV. He sent us this while travelling, adding,

LINE1, which makes up 24% of the genome is NOT “junk,” but an essential part of embryonic development.

The Darwinists are now just completely wrong. IDists predicted this. They pooh-poohed it. Well, they have five tons of egg on their face right now.

NOTA BENE: regarding the “transposons,” it’s quite interesting that it is involved with embryonic development since they are finding that “pseudogenes” are involved in brain (embryonic) development.

IOW, what’s “essential” is what the Darwinists called “junk” (And IDists called fundamental), and what was considered “essential” is only secondarily so.

Alas, no, PaV. Darwinists will simply say that Darwinism predicts this too. It’s all part of the non-falsification package. All that is lacking is a believing public.

From Richard Harris at NPR:

The noted biologist Barbara McClintock, who died in 1992, discovered these odd bits of DNA decades ago in corn, and dubbed them “jumping genes.” (She won a Nobel prize for that finding in 1983.) McClintock’s discovery stimulated generations of scientists to seek to understand this bizarre phenomenon.

Some biologists have considered these weird bits of DNA parasites, since they essentially hop around our chromosomes and infect them, sometimes disrupting genes and leaving illness in their wake. But Miguel Ramalho-Santos, a biologist at the University of California, San Francisco, doesn’t like that narrative.

“It seemed like a waste of this real estate in our genome — and in our cells — to have these elements and not have them there for any particular purpose,” Ramalho-Santos says. “So we just asked a very simple question: Could they be doing something that’s actually beneficial?” More.

“Could they be doing something that’s actually beneficial?” To understand why no one wondered before, one must understand the power of Darwinian groupthink, enforced by wrecking careers. In short, ID guys Jonathan Wells was right and Richard Dawkins was wrong. So was Jerry Coyne. And Michael Shermer.

See also: Note: One junk DNA defender just isn’t doing politeness anymore. In a less Darwinian science workplace, that could become more a problem for him than for his colleagues.

See also: Junk DNA can actually change genitalia.

Junk DNA: Darwinism evolves swiftly in real time

At Quanta: Cells need almost all of their genes, even the “junk DNA”

“Junk” RNA helps regulate metabolism

Junk DNA defender just isn’t doing politeness any more.

Anyone remember ENCODE? Not much junk DNA? Still not much. (Paper is open access.)

Yes, Darwin’s followers did use junk DNA as an argument for their position.

Another response to Darwin’s followers’ attack on the “not-much-junk-DNA” ENCODE findings

Comments
DATCG (101): you referenced a very interesting paper by E. Koonin that is almost a decade old.
The 200th anniversary of Charles Darwin and the 150th jubilee of the "On the Origin of Species" could prompt a new look at evolutionary biology. The 1959 Origin centennial was marked by the consolidation of the modern synthesis. The edifice of the modern synthesis has crumbled, apparently, beyond repair. The hallmark of the Darwinian discourse of 2009 is the plurality of evolutionary processes and patterns. Nevertheless, glimpses of a new synthesis might be discernible in emerging universals of evolution. The biological universe seen through the lens of genomics is a far cry from the orderly, rather simple picture envisioned by Darwin and the creators of the Modern Synthesis.
The Origin at 150: is a new evolutionary synthesis in sight? Koonin 2009 (full text) PDFOLV
July 8, 2018
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gpuccio and DATCG have practically taken over this discussion, at a pace that is hard to catch up with the information avalanche posted in their interesting comments. For example, the referenced papers seem very attractive to anyone who seriously tries to understand what's going on in biology research these days. Thanks!OLV
July 8, 2018
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DATCG: "I’m not concerned about time, except that in terms of unguided events. I see no way unguided, blind mutations have the time to produce the diversity we see. Which I think you and I agree on?" Absolutely! :) "I know that mine is not a popular position admitting “I’m uncertain” of macro-evolution from a single TOL." I am uncertain of a lot of things. Not of design. I have no idea if there is one TOL, or many. But at present I cannot accept that there are no TOL at all. Too many facts are against that idea. For example, I cannot accept, with the facts we know, that metazoa were "created" from scratch, and not using existing single celled eukaryotes. And so on. I do believe that prokaryotes have been used to design mitochondria and plastids. The rest? I don't know. But it is true that a lot of information in eukaryotes seems to derive from prokaryotes too. I don't know why so many people here in the ID filed seem to have a need to deny any form of descent. Maybe it's only a religious position. However, I cannot agree. Descent is there, and it can be observed. Of course, it does not explain functional novelties. But it explains conserved functionalities, and the random degradations that can be observed in them. "I tend to agree with Dr. Sanford at least on a deleterious genome, epigenome, DNA perspective that we’re running down over time with more mutations, not upward bound. As a general overall big picture." That's true. If it were not for design, functions would simply go down, r at most be conserved by some protection procedures. There is no doubt that unguided variation can only degrade function. But that is indeed the strongest argument for descent. We see the gradual degradation, time dependent degradation, in functional (or non functional) structures that are passed on. Neutral variation is everywhere to be seen. I absolutely agree that there are a lot of difficulties with TOL, and Bechly is perfectly right to outline some of them. But that there are difficulties and contradictions does not mean that the idea is completely wrong. That happens all the time in science. The only thing that I am completely sure of is the fundamental role of design in biology: the evidence for that is so overwhelming that it is really astounding for me that a lot of intelligent people can deny it.gpuccio
July 8, 2018
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Oh and speaking of Koonin, I guess a bit off subject, but found this quote at his page on Third Way... Gone, gone... Hsta la Vista Baby, Modern Synthesis is gone... "The summary of the state of affairs on the 150th anniversary of the Origin is somewhat shocking: in the post-genomic era, all major tenets of the Modern Synthesis are, if not outright overturned, replaced by a new and incomparably more complex vision of the key aspects of evolution. So, not to mince words, the Modern Synthesis is gone. " (The Origin at 150: is a new evolutionary synthesis in sight? Trends Genet. Nov 2009; 25(11): 473–475) Poooof!!! ;-) As I continue to see statements like this, it gives me cause for pause to step back and watch, observe as more data and information comes in. If such major constructs are vanished, then what of many other major assumptions? Anyways, stunning admissions! And welcome by Koonin.DATCG
July 8, 2018
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And forgot this one, paper from 2017 on insights and ideas on a "reshaping Darwin's Tree of Life... A bit of hyperbole, but interesting way to look at it I think even from an overall Design perspective. This is in PDF downloadable form at the link below... https://www.researchgate.net/publication/317495996_Reshaping_Darwin's_Tree_Impact_of_the_SymbiomeDATCG
July 8, 2018
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Gpuccio, As usual, your response is detailed :) Thank you for your time and thoughts. I have been and for now in a "I don't know" or "I need more evidence" position. I'm not ruling anything out, but remain unconvinced so far from what I've read in the past. Been in a holding pattern for quite a while as I continue to parse thru different papers and information. I will read the papers you recommended for sure! I agree with many of your comments on stasis, Gould's insights, etc. I saw him as being honest with historical record and data of starts and stops, explosions of information. Even if not convinced of the mechanisms. Certainly on programmed design, function, data and sharing we agree upon. Design can make it all possible. I don't doubt that it could be done, just that I'm uncertain is what done that way - single common ancestor. I can't see it yet in my mind equating to macro-events over time from a single Tree of Life. I know that mine is not a popular position admitting "I'm uncertain" of macro-evolution from a single TOL. I'm not concerned about time, except that in terms of unguided events. I see no way unguided, blind mutations have the time to produce the diversity we see. Which I think you and I agree on? Surely Design can "boost" as you say the genomes, the speed and unfolding processing as it likes as fast or at whatever pace fits the surrounding environments. And of course I agree on allowing Facts guide us. Two explosions ;-) Ediacaran and Cambrian. Darwinist are in a twist, whatever will they do? But because macro events of the past are unobserved and are inferred, I wait, read and digest information as discovered, discussed and debated by all sides. The ancestry can be weaved in many different ways depending upon researchers and their methods(see Gunter Bechly below). So, I enjoy reading and learning, but do wonder how we can ever untangle it all and be certain of so many assumptions in the past even with insights of genetics in the 21st century. As the experts argue, change and move different pieces of the puzzle around and they often disagree. A hundred million years gone, whooosh, or a fossil moved backward, forwards and sideways in time as each expert weighs in. It all seems a lot like throwing darts blindly at times. Also, an aside, or throwing another wrench into the subject ;-) I tend to agree with Dr. Sanford at least on a deleterious genome, epigenome, DNA perspective that we're running down over time with more mutations, not upward bound. As a general overall big picture. I try to keep abreast of Third Way researchers like Shapiro and Koonin, Noble, etc. Koonin especially as he bucks the trends at times in the past and found him to be refreshing with some of his conversations on Darwin's TOL, when others were not watching to close. He was quite excited in several discussions with other Darwinist on the subject. Here's a paper, rather dated from 2010, but enjoyed at time reading it. https://www.nature.com/scitable/topicpage/the-two-empires-and-three-domains-of-14432998 And now that Gunter Bechly was added to the Discovery Team, enjoying reading his articles from time to time... https://evolutionnews.org/2018/06/rafting-stormy-waters-when-biogeography-contradicts-common-ancestry/ So, I remain watchful and will continue to learn! :)DATCG
July 8, 2018
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DATCG: "So is it your opinion TEs and many of the regulatory elements evolved over time with respect to surrounding environments, organisms as well?" Yes. By design, of course. "Part of my issue is the usual chicken/egg scenario. What evolved first or did they progress all in conjunction?" Probably more or less all in conjunction. That's how design usually works. "Did regulatory elements evolve in transition with other surrounding regulatory elements as environment grew and varied around them? And how does this all relate to the Cambrian Explosion of information?" I don't think environment was the only factor, probably not even the most important. I think what we observe is the gradual development of a designed plan, of which environment is a part. The Cambrian explosion is a critical step where the body plans of the different phyla of metazoa are generated. By design, of course. My idea is that transposons are an important tool in that design plan and design process. Because we observe a transposon signature in many of the functional novelties that characterize species. "My other question is, why is it limited to a One-Time event? Surely if we had an event in the past of information explosion, then why do we see stasis now? Would we not find some evidence of macro-generative changes taking place around our globe? But what we find everywhere is equilibrium, balance, and the tips of branches extended as far as they can go. Just some thoughts." But, of course, stasis is prevalent throughout natural history. Gould understood that very well. We have the (probable) very long stasis between prokaryotes and eukaryotes (even if we don't really know when and how eukaryotes appeared). We have the quite certain stasis between single celled eukaryotes and metazoa (either the Ediacaran or the Cambrian explosion). Vertebrates emerge rather quickly from deuterostomia about 100 million years after the Cambrian explosion. And so on. It seems that design is rather sudden in natural history, often confined to specific boosts. I have no idea if design is implemented gradually, or in rather sudden events. Many facts are in favor of the second option, but again only facts must guide us. If design happens rather suddenly, it could happen in one million years, or one thousand, or one year. Maybe one day, or one second. Everything is possible, and again only facts must guide our understanding. For the moment, I like to think that design happens in rather sudden critical events, like the Cambrian explosion, but that it takes some time anyway. It is also likely that minor events of design happen more gradually and more constantly. And, of course, it is possible that minor minor events of adaptation, either random or according to pre-designed algorithms, contribute to the whole process. In all cases, our window of direct observation (hundreds of years) is certainly too small to give us any reasonable probability to witness major design events. We are probably only observing stasis. Luckily, however, we can well observe things indirectly. "The organisms, bacteria, plants, eukaryotes, etc., seem very difficult to explain as symbiosis w/o pre-existing architecture. Bio-Codes built-in that can accept the input data from it’s surroundings. Not sure how you see this." I don't think symbiosis has a major role in all that. Maybe only occasionally (mithocondria and plastids are the best example). "Even then the complexity or ability to change and achieve a progression of increasing functional enhancements is quite a marvel of technology." It is. "I’m having a hard time wrapping my head around Designed macro-evolution because it seems like there are huge issues unless the functional relationships are all Prescribed." Why shouldn't they? "This is why I tend to think we have multiple bases of life, or bushes of life if you will, not a single Tree of Life." It's possible, but not really necessary. Let's take the Cambrian explosion, for example. The phyla are certainly different and complex designs. Each of them individually programmed. But we have good reasons to believe, form facts, that all of them use a shared bulk of functionality which had already been designed in single celled eukaryota. IOWs, both chordata and sponges, just to be clear, are built using similar eukaryotic cells. Even if the paln is completely different. So, we have two possibilities: a) An original common ancestor of metazoa originated from single celled eukaryotes, and then quickly was differentiated (by design) into the differnt phyla. Or: b) Each phylum emerged by individual design from single celled eukaryotes. OK, both scenarios are possible, and probably at present I would favor b), because I am not sure we have convincing evidence of a common ancestor of metazoa. But my point is: in both cases we have a tree, and not only "bushes". Even if there was not a common ancestor of metazoa, single celled eukaryotes are certainly a common ancestor. There is a lot we don't understand. For example, I am really fascinated by the Ediacaran explosion, and I would really like to know what those beings were, and any detail about their biological information. Who knows, maybe in the future? "I realize these last few statements may sound weird, but in order lets say for an organism to respond to surrounding organisms, does it not need original regulatory features to react, digest and respond?" Of course. They are certainly part of the design. Even admitting a small role for adaptation, as I have said before. "I think it’s one thing for insertions of horizontal gene transfer, yet quite another for the host to recognize and develop the regulatory actions to utilize the new informational units, is it not? Especially if there’s some form of transition allocated to the human genome for example, or mammals in general." Of course. When I say that transposons (or HGT) are tools of design, I mean exactly that: they are used by the designer in a greater context. "I tend to think there’s so much more we still do not understand in the Codes of Life." And I absolutely agree! :)gpuccio
July 8, 2018
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Gpuccio, Thanks! So is it your opinion TEs and many of the regulatory elements evolved over time with respect to surrounding environments, organisms as well? Part of my issue is the usual chicken/egg scenario. What evolved first or did they progress all in conjunction? Did regulatory elements evolve in transition with other surrounding regulatory elements as environment grew and varied around them? And how does this all relate to the Cambrian Explosion of information? My other question is, why is it limited to a One-Time event? Surely if we had an event in the past of information explosion, then why do we see stasis now? Would we not find some evidence of macro-generative changes taking place around our globe? But what we find everywhere is equilibrium, balance, and the tips of branches extended as far as they can go. Just some thoughts. The organisms, bacteria, plants, eukaryotes, etc., seem very difficult to explain as symbiosis w/o pre-existing architecture. Bio-Codes built-in that can accept the input data from it's surroundings. Not sure how you see this. Even then the complexity or ability to change and achieve a progression of increasing functional enhancements is quite a marvel of technology. I'm having a hard time wrapping my head around Designed macro-evolution because it seems like there are huge issues unless the functional relationships are all Prescribed. This is why I tend to think we have multiple bases of life, or bushes of life if you will, not a single Tree of Life. I realize these last few statements may sound weird, but in order lets say for an organism to respond to surrounding organisms, does it not need original regulatory features to react, digest and respond? I think it's one thing for insertions of horizontal gene transfer, yet quite another for the host to recognize and develop the regulatory actions to utilize the new informational units, is it not? Especially if there's some form of transition allocated to the human genome for example, or mammals in general. At least, this is where I scratch my head on some of the issues and resulting claims transferred to Eukaryotes as a possible solution. I tend to think there's so much more we still do not understand in the Codes of Life. Thanks again, will enjoy reading these! :)DATCG
July 7, 2018
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DATCG: Here are a few recent papers: Transposons: a blessing curse. https://www.sciencedirect.com/science/article/pii/S1369526617301577?via%3Dihub
The genomes of most plant species are dominated by transposable elements (TEs). Once considered as ‘junk DNA’, TEs are now known to have a major role in driving genome evolution. Over the last decade, it has become apparent that some stress conditions and other environmental stimuli can drive bursts of activity of certain TE families and consequently new TE insertions. These can give rise to altered gene expression patterns and phenotypes, with new TE insertions sometimes causing flanking genes to become transcriptionally responsive to the same stress conditions that activated the TE in the first place. Such connections between TE-mediated increases in diversity and an accelerated rate of genome evolution provide powerful mechanisms for plants to adapt more rapidly to new environmental conditions. This review will focus on environmentally induced transposition, the mechanisms by which it alters gene expression, and the consequences for plant genome evolution and breeding.
Transposable elements shape the human proteome landscape via formation of cis-acting upstream open reading frames. https://onlinelibrary.wiley.com/doi/abs/10.1111/gtc.12567
Abstract Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis-acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed "transposon-derived upstream ATGs" or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non-ATG trinucleotides of integrated transposons. Among these non-ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation-mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human-specific upstream ATG formation within transposon sequences in 5' untranslated regions after divergence between human and nonhuman primates. Methylation-mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease-related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis-acting uORF creation.
Genetic exchange in eukaryotes through horizontal transfer: connected by the mobilome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791352/
Abstract Background All living species contain genetic information that was once shared by their common ancestor. DNA is being inherited through generations by vertical transmission (VT) from parents to offspring and from ancestor to descendant species. This process was considered the sole pathway by which biological entities exchange inheritable information. However, Horizontal Transfer (HT), the exchange of genetic information by other means than parents to offspring, was discovered in prokaryotes along with strong evidence showing that it is a very important process by which prokaryotes acquire new genes. Main body For some time now, it has been a scientific consensus that HT events were rare and non-relevant for evolution of eukaryotic species, but there is growing evidence supporting that HT is an important and frequent phenomenon in eukaryotes as well. Conclusion Here, we will discuss the latest findings regarding HT among eukaryotes, mainly HT of transposons (HTT), establishing HTT once and for all as an important phenomenon that should be taken into consideration to fully understand eukaryotes genome evolution. In addition, we will discuss the latest development methods to detect such events in a broader scale and highlight the new approaches which should be pursued by researchers to fill the knowledge gaps regarding HTT among eukaryotes.
This one is specially interesting: Protein coding genes as hosts for noncoding RNA expression. https://www.sciencedirect.com/science/article/pii/S1084952117300496?via%3Dihub
Abstract With the emergence of high-throughput sequence characterization methods and the subsequent improvements in gene annotations, it is becoming increasingly clear that a large proportion of eukaryotic protein-coding genes (as many as 50% in human) serve as host genes for non-coding RNA genes. Amongst the most extensively characterized embedded non-coding RNA genes, small nucleolar RNAs and microRNAs represent abundant families. Encoded individually or clustered, in sense or antisense orientation with respect to their host and independently expressed or dependent on host expression, the genomic characteristics of embedded genes determine their biogenesis and the extent of their relationship with their host gene. Not only can host genes and the embedded genes they harbour be co-regulated and mutually modulate each other, many are functionally coupled playing a role in the same cellular pathways. And while host-non-coding RNA relationships can be highly conserved, mechanisms have been identified, and in particular an association with transposable elements, allowing the appearance of copies of non-coding genes nested in host genes, or the migration of embedded genes from one host gene to another. The study of embedded non-coding genes and their relationship with their host genes increases the complexity of cellular networks and provides important new regulatory links that are essential to properly understand cell function.
gpuccio
July 7, 2018
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As a follow up on Introns, came across this article tonight and find it fascinating. Not had time to read it all. From 2014... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989599/ Requirement for highly efficient pre-mRNA splicing during Drosophila early embryonic development Leonardo Gastón Guilgur,1,2,3 Pedro Prudêncio,1,2,3 Daniel Sobral,1 Denisa Liszekova,1 André Rosa,1 and Rui Gonçalo Martinho1,2,3,* Elisa Izaurralde, Reviewing editor Elisa Izaurralde, Max Planck Institute Development Biology, Germany; What they discovered is Intron-less usage during early embryonic development since Splicing takes to long.
Consistently, approximately 70% of early zygotic genes are small in size and intronless (De Renzis et al., 2007). As only 20% of Drosophila genes are intronless, it has been proposed that small intronless genes have an important selective advantage for transcription during the syncytial blastoderm formation (De Renzis et al., 2007).
What I'm thinking is an inner core is protected(not much splicing if any), an outer core later is elevated and expressed(splicing) along with historic input of genes from a mother and father donors. This does not consider the many epigenetic factors during pregnancy that can improve upon or be deleterious to the offspring. This is way over generalized on my part. And I've not verified if this carries across to the human genome. Well, found a database with comparison... http://www.sinex.cl/statistics I find this fascinating and wonder if this limits major macro variation by some extent, but allows Edge-of-the-Genome variation.DATCG
July 6, 2018
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Forgot to add this list of databases for lncRNA from Wiki... https://en.wikipedia.org/wiki/List_of_long_non-coding_RNA_databasesDATCG
July 6, 2018
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Gpuccio @91 continued...
f) Finally, we must not forget that non codng DNA, and especially its transposable component, have probably an important role not only in regulating the individual, but in shaping the evolution of species,
I agree up to this point above. I'm in an observation mode for the rest of your conclusion...
"serving as powerful design tools in the creation of new genes, new proteins, new regulatory networks and so on, as suggested by an abundant amount of literature.
Much literature suggest this. What I'm unsure of is in regards to Macro events.
The transposonic origin of many new protein genes, for example, has been proved in many cases, and transposons are now one of the best scenarios for the interpretation of evolutionary history. And, in the perspective of us IDists, of its designed origin. ;-)
Can you please share a few research examples? I know there are many, but which papers do you recommend for Eukaryote macro evolutionary transitions? I'll read and review as I have time. I've read some general papers on evolution and transposons and species. I've read material on retrotransposons fascinating stuff. For human genome they're importance. Again, use to be thought of as "JUNK". Thanks always for your contributions here and taking time for explanations. Really enjoy your input and detailed responses.DATCG
July 6, 2018
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Gpuccio @91, thanks for the review... a) yep, and as regulator elements, to me at least this does not seem to surprising, which leads us to efficiency concepts later that might be reviewed the more we understand developmental aspects and species specific mechanisms. And how each interface or react for groupings and individual organisms within their environments b) agreed, but are you tying this in to Flexible Folding, or as usually tagged Intrinsically Disordered Proteins? c) Yep, yep and yep :) It's really cool and it's really all about the programming, flexible programming made available by highly Modifiable Data Elements and what I'd call Environmental Pre-programmed Response Programs d) the Junk of Junk ... more treasure?!? "As I have discussed at #78, giving the example of FIRRE, many lncRNAs are polyexonic. For example, FIRRE 1 is made from 13 different exons And I absolutely loved this I'm guessing you know!? It reminds me of our discussions under the Spliceosome and Intronic functionality, dual functions, etc. Yes, I agree, there're more treasure to find I think of functional outcomes for these Introns. Essentially what we have is modular coding, the ability to absorb incoming messages like stress-related events or environmental queues in which certain aspect ratios, or triggers may drive alternative splicing outcomes. Again, this appears to be a Direct Access Method of Alternative Data Retrieval Dependency on Input or Program Recognition. It's just too cool! e) hehe! yep! :) OK, so what we're discovering is incredible factors of a Direct Access Processing Tree driven by surrounding physical elements, internal elements and features elements that can be updated, changed and removed on the fly. And change from individual to individual down line or across groupings. Now, there are Critical Cores for survival and then there are Features - the Uniqueness - of different species, outcomes and "beauty" or "beast" lets say. It's quite staggering and awe-inspiring to learn. Splicing and Introns/Exons an actual Must here. And a huge Advantage for multiple outcomes. Darwinist have made judgments in error I think that this amount of "JUNK" is bad design, prior to even knowing how it is utilized, called and functions. The process of life must do all of this physically while maintaining incredible accuracy, energy input, error-checking and removal of errors efficiently, rapidly and within narrow time frames or die off. It must also have pre-built Recognition factors, or none of this works. Location and Addressing.DATCG
July 6, 2018
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DATC: Again, excellent points at #89 and #90! :) A few personal thoughts: a) Conservation. In general, non coding RNAs are not very conserved. However, the degree of conservation can vary a lot between different forms. Satellite DNA, for example, is more conserved. lncRNAs are often scarcely conserved. Some are conserved in mammals, others are not. Some that are conserved in mammals are not conserved in other vertebrates. And so on. This amazing variety of conservation can mean many different things, as discussed in the following points. b) Sequence-structure-function relationship. We still understand very little about this, but it seems rather clear that the relationship between sequence, structure and function is very different in functional RNAs than it is for proteins. Structure seems to be fundamental for function, but it probably is less strictly related to sequence. That can allow for much greater flexibility of the sequence in functional RNAs, as it happens for proteins with low functional sequence specificity. c) Possible restricted specificity of function. If what we have been discussing here is even partially true, it seems very likely that lncRNAs and other forms of non coding RNAs are extremely important tools of transcription regulation. That would make them central in the procedures that define the specific nature of species, or of cell types. The procedure, or at least part of them. That mean, of course, that much of their "divergence" from species to species could well be functional divergence: that kind of difference that is there to do different things. d) Junk of junk? I absolutely agree with what you say about introns. But then what should we say of the "introns" of "junk" DNA? As I have discussed at #78, giving the example of FIRRE, many lncRNAs are polyexonic. For example, FIRRE 1 is made from 13 different exons. Moreover, as it happens for proteins, introns are much bigger than exons in lncRNAs too. In the case of FIRRE 1, the 13 exons correspond to "only" 2928 bp from a region of about 140,000 bp. The rest, of course, goes into the 12 introns. But, because, of alternative splicing, at least 22 different transcripts are derived form the same region, with different exon-intron diversification. So, what about these big introns in non coding genes? Are they the junk of junk? Or, as you will probably agree, are they even more sophisticated levels of functional regulation? e) Huge functional perspectives. As we have seen, lncRNAs are transcribed (and spliced) from vast regions of non coding DNA, often intergenic, repetitive or not, but also from coding sequences, often antisense, introns, or some mix of that all. As each lncRNA is, in the end, a specific selection of partial sequences (exons), reconstructed in a specific way by alternative forms of splicing, and as the function of those lncRNAs is probably connected to the final structure, more than to the strict sequence, it seems rather obvious that there are almost infinite functional potentialities. IOWs, a designer can "write" all sorts of functional RNAs, all sorts of regulatory tools, from the genome and its huge non coding territories, if he can control the way those partial sequences are transcribed, and above all spliced. IOWs, the whole genome, and above all its vast non coding spaces, are a potential repository for huge, almost infinite, regulatory chances, in the hands of an intelligent designer who can tweak their transcription and splicing. f) Finally, we must not forget that non codng DNA, and especially its transposable component, have probably an important role not only in regulating the individual, but in shaping the evolution of species, serving as powerful design tools in the creation of new genes, new proteins, new regulatory networks and so on, as suggested by an abundant amount of literature. The transposonic origin of many new protein genes, for example, has been proved in many cases, and transposons are now one of the best scenarios for the interpretation of evolutionary history. And, in the perspective of us IDists, of its designed origin. :)gpuccio
July 4, 2018
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OLV @86, Much of the work is being done in some ways by current Epigenetic researchers(see some links I posted above). But I guess I'm hinting at or hoping Discovery Institute :) might consider accessing those databases, tracking and building a Junk to Func Listing as it continues to build. Maybe it can be done in generalized terms too of overall percentages and mega data. For example - ALUs, LINEs, etc., in groupings. Add up the percentages and compare to those specified by Darwinist who claimed it all to be JUNK, or now, reducing it to "at least" 75% in the case of Dan Graur. I think it would be an interesting project for DI to do. My thoughts are that once you find a few "JUNK" regions or groupings like ALUs have Function, most likely much if not all of them May have function. But Darwinist assume the direct opposite or that as they say, "just because you find function in a few ALUs, does not translate to ALL of them having function." That's an assumption on their part. But so is mine if Designed. Which assumption is correct, time will tell. And thus an idea to track it over time and see if the Function of former "JUNK" DNA regions surpasses Graur's 75% threshold. If it does, that wall falls for him and others staking out a very strong claim. Though I suspect they might retreat and claim another threshold. Thus again, another good reason to track the Junk to Func progress :) Edit: I do want to be careful in my statements. I'm not stating that all of formerly declared regions of "JUNK" DNA will have function. Surely there may be fault-tolerance built in for duplicates and discarded remnants that eventually is released after non-use. But there's a full system of monitoring and degradation built in to remove and discard unwanted data in the genome. I don't know how much is functional. But suspect it's higher than Dan Graur's threshold of 75% Junk for eukaryotes, especially humans. And another important caveat. I consider Introns(some found functional already) as another argument for Design in use by the Spliceosome. Darwinist wrote these off long ago. But for a designed system of storage and retrieval from a Coders point of view. It makes all the sense in the world. I recognize these units as smaller elements and tools of the broader Regulatory System. They may seem like "junk" or repeating patterns and easily tossed aside. But for a Coder, we often use repeating elements and data patterns for different variety of targeted data retrieval, modifications, identifiers in exchange for pre-programmed responses. The introns are being read. Just becaused they're discarded does not lead to non-functional. They include formal elements of utilization. This is like a table of functional queues built-in that reduces the need for hard-coding.DATCG
July 3, 2018
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#84-85 OLV, Great! Yep... as it would be if you're designing code, storage, retrieval, copying and replication processing! We do this routinely with all kinds of massive data today and code. We replicate, but tag, id and modify it on the fly. And the structures contain location data as well as modifier data often a few bytes down or maybe in another "domain" if you like. Thus the need for "random" access and Tagging of data. But it's not really random. It only appears that way. Darwinist are still stuck in the past, using antiquated assumptions. It's an architecture of interspersed elements. While this requires Splicing - this is much more advantageous than storing the needed IDs, Tags, Enhancers, Silencers in a whole other "table." This bypasses inefficient methods of retrieval(when possible - not always) by storing Regulatory ID Elements(RIDErs) in direct contact with Readers and Editors for Direct Access, On the fly processing. So the Darwinist think-assume this is inefficient. Far from it, it's highly optimized layers upon layers of Code and Data intertwined with each other. Bill Gates of Microsoft fully understood this as do many coders that had to work with complex storage requirements, modification and updates, retrieval and efficiency. This allows efficient manipulation, while conserving the original structures intact as required for preserving data and extending life by replication. It also allows a very convenient and efficient method of updating these elements with surrounding input data from the environment as it is encountered, or as stress and other issues are recognized by the myriad of systems interacting with each other. Once we can decipher these codes, the elements and architecture, the findings will be profound for Design Therapy of individual care. It's already happening on small scales. We already know Epigenetics allows real time response to the environment. Which is not Darwinian, but controlled systems responses. Decoding the different elements and functions will allow much better response mechanisms to well known diseases, including variants of individual epigenomes. It appears Mung is going to be rich one day ;-)DATCG
July 3, 2018
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#82 PaoloV, Thanks! I'll check out the video when I have time. Yep, the article and paper are good JUNK ;-)DATCG
July 3, 2018
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Mung @83, Oooops, let the cat outta the bag! ;-) from 2012... "“Cat herder in chief” of the ENCODE consortium of 400 geneticists from around the world" Thar be "hidden treasure" in that thar bag o'Junk... https://www.scientificamerican.com/article/hidden-treasures-in-junk-dna/DATCG
July 3, 2018
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DATCG (80): I like your idea on "Large JUNK to FUNC tracking Database site". How would that look? Would that be a blog?OLV
July 3, 2018
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the non-coding nature and lack of conservation in repeat sequence among closely related species led to the idea that they are mostly junk DNA, serving no essential function (Walker, 1971; Doolittle and Sapienza, 1980).
Instead, we propose that satellite DNA is a critical constituent of eukaryotic chromosomes to ensure encapsulation of all chromosomes in interphase nucleus. Our results may also explain why the sequences of pericentromeric satellite DNA are so divergent among closely related species, a contributing factor that led to their dismissal as junk.
A conserved function for pericentromeric satellite DNAOLV
July 3, 2018
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‘Junk DNA’ therefore appears to participate in fundamental cellular processes across species, a result that opens up several new lines of research.
A conserved function for pericentromeric satellite DNAOLV
July 3, 2018
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You guys need to stop. I've been buying up "junk-DNA" for next to nothing and you guys are going to do nothing buy drive up the costs. And there goes my retirement fund.Mung
July 3, 2018
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DATCG: Very interesting information that you posted in your comments above. Thanks. Your comment at # 72 refers to a very exciting EN article that mentions the U. Michigan scientist Yukiko Yamashita, who said a few interesting things in this interview last year at the CSHL 82nd Symposium Here's more info on Yukiko Yamashita's work at the U. of Michigan, Ann ArborPaoloV
July 3, 2018
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Gpuccio, Thanks for links! :) Yep, I've been following lncRNAs for a while now for my own reasons, along with circRNAs and many other Smart "Junk" ;-) on brain functionality. Great stuff! Thank you! OLV, Gpuccio, More than one "mechanism of action..." The paper Gpuccio linked @77 is dated June 26, 2018...
However, to date, only a small percentage of these lncRNAs has been described in the literature, with an even smaller number being attributed to a specific mechanistic function. Furthermore, like proteins, many lncRNAs can employ more than one mechanism of action.
So, what are scientist now and what will researchers find more of in the future? Note that this has become a Coding issue? To seek out patterns and reverse engineer them. My suspicion is, each pattern and placement will be much like any Data Coding requirements. The only way to track and control such complex systems is to intersperse the systems with IDentifiers, Tags, and other elements and patterns to regulate the building blocks of life. This is very much a Reverse Programming exercise now and has been for quite some time. But with the advent of regulatory functions, ENCODE and disease research, the true wealth of knowing how to reverse engineer Designed Code will be a fundamental aspect of research going forward. You're no longer asking how something accidentally came together. They're researching how these many Codes in the system controls, monitors, repairs and reacts to disease, stress, environments, food, etc., etc. Including how the many Codes organize and interact in a flow reaction process. Maybe we will see a new set of Rules based understanding of regulatory features, changes and reactions for the multiple Codes in the system. Cannot mutate this "JUNK" without severe consequences? Of disease, cancer, interrupted development processes? It's amazing to see this research all unfold and supports Design. We live in great times of Code discovery and function!DATCG
July 2, 2018
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OLV @79, "At what point could such an accelerated growth of research papers slow down?" Great question! :) Considering this started around 2012 in full force? And approximately 90-95% was considered "JUNK" by Darwinist for decades of little research? They're still discovering new information on how the 1-2% Protein coding genes function! Coordinate and organize. :) Haha! That's why I think we need a Large JUNK to FUNC tracking Database site ;-) This is going to go on for decades and smart scientist who desire to make a huge impact in Disease and Cancer treatments of all kinds are leaping into Epigenetic Regulatory Function Research on larger scales now. It's bigger than any gold rush and we're only seeing the beginning. The smart companies and scientist are going full throttle on this. Because Epigenetics disease research allows individual treatments as well. It's like we've just discovered thars gold and now thars a rush on to buy permits. We're in the very beginning of this process and it will be amazing for treatment of disease, even I would think aging and other factors. Edit: And just to add, they're still designing and implementing systems to discover, monitor, organize and research these new patterns and integrations of "JUNK"! They're at the phase of determining best how to mine all this treasure.DATCG
July 2, 2018
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gpuccio (77): “...papers in Pubmed corresponding to a “lncRNAs” query were just 111 in 2012. Their number has been increasing at a very fast rate, and they are 1583 in 2017, and 1198 already in 2018.” Interesting statistics. At what point could such an accelerated growth of research papers start to slow down?OLV
July 2, 2018
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DATCG: Here is a very interesting database of human annotated lncRNAs. It includes at present 120,353 transcripts from 51,382 genes. What is really amazing is the complexity of those transcripts. Just as an example, look at the FIRRE gene. This is the brief summary from Wikipedia:
Firre (functional intergenic repeating RNA element) is a long non-coding RNA located on chromosome X. It is retained in the nucleus via interaction with the nuclear matrix factor hnRNPU.[4] It mediates trans-chromosomal interactions[4] and anchors the inactive X chromosome to the nucleolus.[5] It plays a role in pluripotency[6] and adipogenesis.[7]
But things are much more complex. The FIRRE region is located on chromosome X, and includes a sequence of about 140,000 bp. From that region, 22 different known lncRNA transcipts are derived, numbered from FIRRE 1 to FIRRE 22. FIRRE 1, for example, is 2928 bp long. But the interesting thing is that it is derived from 13 exons, dispersed thorugh the whole 140,000 bp region. So, it seems that the whole region is trancribed, and 12 very big introns are spliced before the FIRRE 1 transcript emerges. Of course, the 21 remaining FIRRE transcripts are derived from the same region, but through completely different transcriptional histories. The longest, for example, is FIRRE 12, 8415 bp long, made by 13 exons too. The shortest seems to be FIRRE 6, 259 bp long. Still long enough top be defined as a lncRNA, indeed (the conventional limit is at 200 bp). But are these weird transcripts functional? That seems to be the case. This is one of the many papers about FIRRE: The lncRNA Firre anchors the inactive X chromosome to the nucleolus by binding CTCF and maintains H3K27me3 methylation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391730/ And this is very recent: The NF-?B–Responsive Long Noncoding RNA FIRRE Regulates Posttranscriptional Regulation of Inflammatory Gene Expression through Interacting with hnRNPU https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672816/ Ever new complexity...gpuccio
July 2, 2018
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DATCG: Thank for your excellent contributions, as always! :) Yes, the subject is exciting and really, really in huge development. Here is an extremely recent overview, with special attention to the techniques that can be used in studying lncRNAs function: Platforms for Investigating LncRNA Functions http://journals.sagepub.com/doi/10.1177/2472630318780639
Abstract Prior to the sequencing of the human genome, it was presumed that most of the DNA coded for proteins. However, with the advent of next-generation sequencing, it has now been recognized that most complex eukaryotic genomes are in fact transcribed into noncoding RNAs (ncRNAs), including a family of transcripts referred to as long noncoding RNAs (lncRNAs). LncRNAs have been implicated in many biological processes ranging from housekeeping functions such as transcription to more specialized functions such as dosage compensation or genomic imprinting, among others. Interestingly, lncRNAs are not limited to a defined set of functions but can regulate varied activities such as messenger RNA degradation, translation, and protein kinetics or function as RNA decoys or scaffolds. Although still in its infancy, research into the biology of lncRNAs has demonstrated the importance of lncRNAs in development and disease. However, the specific mechanisms through which these lncRNAs act remain poorly defined. Focused research into a small number of these lncRNAs has provided important clues into the heterogeneous nature of this family of ncRNAs. Due to the complex diversity of lncRNA function, in this review, we provide an update on the platforms available for investigators to aid in the identification of lncRNA function.
This final consideration is really telling:
Upon the identification of regulatory ncRNAs, it has now become readily apparent that regulation of proteins has been completely underestimated. We are now only beginning to understand that signal transduction is dependent upon, as it appears to us today, an almost incalculable level of regulation within a signaling cascade if not at the individual protein level. This continuous dynamic regulation is necessary for cells to finetune external cellular signaling cues into appropriate transcriptional responses. The identification that loss-of-function mutations within ncRNAs contribute to the genesis and progression of human disorders further highlights their importance.
Emphasis mine. It's very interesting that presently the best method to target lncRNAs, and therefore to understand their functions, is through oligonucleotide-based strategies. And that's exactly what was done in the paper about LINE derived RNAs which started this very interesting discussion. By the way, papers in Pubmed corresponding to a "lncRNAs" query were just 111 in 2012. Their number has been increasing at a very fast rate, and they are 1583 in 2017, and 1198 already in 2018. And a lot of them are about important and very interesting medical issues!gpuccio
July 2, 2018
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and this project...
We show that PREDICTD data captures enhancer activity at noncoding human accelerated regions. PREDICTD provides reference imputed data and open-source software for investigating new cell types, and demonstrates the utility of tensor decomposition and cloud computing, both promising technologies for bioinformatics.
PREDICTD PaRallel Epigenomics Data Imputation with Cloud-based Tensor Decomposition hmmm, the link, app is not working or timing out, but here's the link at Twitter. Click on the link at the ENCODE Twitter message. It still may run a bit slow for some reason at NATURE link... https://twitter.com/EncodeDCC/status/984131983067377664
Understanding how the genome is interpreted by varied cell types, in different developmental and environmental contexts, is the key question in biology. With the advent of high-throughput next-generation sequencing technologies, over the past decade, we have witnessed an explosion in the number of assays to characterize the epigenome and interrogate the chromatin state, genome wide. Assays to measure chromatin accessibility (DNase-seq, ATAC-seq, FAIRE-seq), DNA methylation (RRBS, WGBS), histone modification, and transcription factor binding (ChIP-seq) have been leveraged in large projects, such as the Encyclopedia of DNA Elements (ENCODE)1 and the Roadmap Epigenomics Project2 to characterize patterns of biochemical activity across the genome in many different cell types and developmental stages. These projects have produced thousands of genome-wide datasets, and studies leveraging these datasets have provided insight into multiple aspects of genome regulation, including mapping different classes of genomic elements3,4, inferring gene regulatory networks5, and providing insights into possible disease-causing mutations identified in genome-wide association studies (GWAS)2.
DATCG
July 2, 2018
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Thar's gold in them thar "JUNK" regions. Just ask ENCODE DCC on twitter... Jobs, Jobs, Jobs... https://twitter.com/EncodeDCC/status/996859770521841664
@EncodeDCC May 16 More... ENCODE DCC is looking for associate data wranglers! Please share to graduating students and those interested in databases/bioinformatics! https://app.joinhandshake.com/jobs/1613818/share_preview … via @joinhandshake
Assistant Biocuration Scientist - Stanford School of Medicine Less than 2% of the human genome sequence is protein coding, have you ever wondered what is the role of the remaining 98% of the genome?
uh, no, not Dan Graur or Darwinist stuck in Neutral.
Stanford University Department of Genetics has an excellent opportunity for an entry-level Assistant Biocuration Scientist to play a role in the ENCODE project, advancing our understanding of the human genome and determining how genetics influences the development and progression of diseases. The ENCODE project is funded by National Institute of Health and is building a catalog of all the functional elements in the human genome sequence, subsequently making it available to scientists worldwide for the study of human health and disease.
Shift out of neutral, hit the pedal and Go ENCODE.DATCG
July 2, 2018
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