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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
In any case you guys are doing a formidable job. Thanks.PeterA
August 5, 2018
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Here’s another : Journal of the Association for Information Science and Technology Volume 66, Issue 11 RESEARCH ARTICLE Growth rates of modern science: A bibliometric analysis based on the number of publications and cited references Lutz Bornmann Rüdiger Mutz First published: 29 April 2015 https://doi.org/10.1002/asi.23329PeterA
August 5, 2018
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Sorry, I incorrectly wrote “4-year old” instead of “6-year old”.PeterA
August 5, 2018
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A few guys (gpuccio, DATCG, lately OLV) are posting many references to biology papers, making the rest of the readers here wonder how they manage to find so many interesting papers in such a short time. I found this 4-year old article that seems to shed some light on the subject: Publication Growth in Biological Sub-Fields: Patterns, Predictability and Sustainability Marco Pautasso Received: 12 June 2012; in revised form: 5 November 2012 / Accepted: 19 November 2012 / Published: 23 November 2012 Abstract : Biologists are producing ever-increasing quantities of papers. The question arises of whether current rates of increase in scientific outputs are sustainable in the long term. I studied this issue using publication data from the Web of Science (1991–2010) for 18 biological sub-fields. In the majority of cases, an exponential regression explains more variation than a linear one in the number of papers published each year as a function of publication year. Exponential growth in publication numbers is clearly not sustainable. About 75% of the variation in publication growth among biological sub-fields over the two studied decades can be predicted by publication data from the first six years. Currently trendy fields such as structural biology, neuroscience and biomaterials cannot be expected to carry on growing at the current pace, because in a few decades they would produce more papers than the whole of biology combined. Synthetic and systems biology are problematic from the point of view of knowledge dissemination, because in these fields more than 80% of existing papers have been published over the last five years. The evidence presented here casts a shadow on how sustainable the recent increase in scientific publications can be in the long term. http://www.mdpi.com/2071-1050/4/12/3234/htmPeterA
August 5, 2018
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Off topic questions: Unconventional RNA-binding proteins: an uncharted zone in RNA biology. RNA–protein interactome studies suggest complex crosstalk between RNA and other well?established cellular functions. complex crosstalk? huh? The GAIT translational control system: The interferon (IFN)-y-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally related genes. transcript-selective translational control? huh? Promiscuity in post-transcriptional control of gene expression: Drosophila sex-lethal and its regulatory partnerships how such a seemingly ‘simple’ RNA-binding protein can exert this plethora of different functions? seemingly ‘simple’? huh?OLV
August 5, 2018
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Gpuccio @158, will do :) Had no idea that discussion was still ongoing! Ha! You have many post still stirring the proverbial Darwin pot I see :)DATCG
July 27, 2018
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DATCG: You could also have a look at this new comment of mine answering bill cole: it clarifies better the views I expressed at #157: https://uncommondescent.com/intelligent-design/defending-intelligent-design-theory-why-targets-are-real-targets-propabilities-real-probabilities-and-the-texas-sharp-shooter-fallacy-does-not-apply-at-all/#comment-662187gpuccio
July 27, 2018
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DATCG: Your questions are always stimulating! :) "Do you think we will be able to find common mechanisms in the future that accounts for “convergence” which is often an appeal by Darwinist to solve a very complex problem for them as a blind series of events across multiple life forms?" "Convergent" evolution really makes sense in a design perspective. It is simply an example of "convergent solutions". The same problem can be solved in different ways, or even in similar ways, bu in different contexts. Design is a process which starts from ideas, from conscious models, and is realized and implemented by specific programming solutions. We know that flight has appeared independently in many different lines of animals: insects, birds, mammals. Of course there is something in common in those solutions, because the problem is similar, but the solutions themselves are very different. My model of descent is very powerful to explain that. Where specific implementations are re-used, at the level of specific code, for example the specific sequence of a protein in different species, it is very likely that the code has been physically transerred, and re-used. But when it's the general idea that is re-used, with differne specific codes, then there is probably no physical derivation, only a similarity in the idea itself. Those concepts remain valid both in the case of one designer or in the case of multiple designers. "Do you think evolution of macro changes in life forms has stopped?" Good question. There is no reason, IMO, to think that it has stopped. Biological design has certainly been active till very recently in evolutionary history (look at us humans, for example). However, I don't think that we have at present reliable facts to decide.gpuccio
July 26, 2018
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OLV @153, You and me both ;-)DATCG
July 25, 2018
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Gpuccio @152 and John_a_Designer @151, John, Good points and questions. Gpuccio, Nice summary yet again, in your response. Gpuccio, Do you think we will be able to find common mechanisms in the future that accounts for "convergence" which is often an appeal by Darwinist to solve a very complex problem for them as a blind series of events across multiple life forms? And a bit off topic maybe, but a question that always keeps me fascinated in the unfolding aspect of life from the past to the present form(s). Do you think evolution of macro changes in life forms has stopped?DATCG
July 25, 2018
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Researchers have captured video showing how pieces of DNA once thought to be useless can act as on-off switches for genesOLV
July 24, 2018
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gpuccio, DATCG: I’m trying to process the interesting information you’ve posted lately. Really hard to catch up. Definitely you have preemptively overwhelmed any potential opponent in this discussion. Well done! Thanks.OLV
July 21, 2018
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john_a_designer: Yes, I am aware that many proteins and systems that are really aimed at multicellularity do appear before. I have read your comments, and I think that essentially I do agree with you. Of course all this is completely incompatible with blind watchmakers of any kind, while it makes perfect sense in the light of design. As you may know, I believe in descent by design, and I think that a gradual implementation of design plans is definitely a possibility. As I have said many times, my idea of descent is simply that functional modules are reused in new plans, but they are reused as they are in existing organisms, and they carry with them all the random non functional variations that are the signature of elapsed time. Of course, all that is functionally new must be designed, either "de novo" or by substantial re-engineering what already exists. We don't know how suddenly new plans appear, that is something that will have to be answered by facts, in time. But there is definitely a general plan which evolves through living beings, and its main purpose seems to be to manifest a growing variety and depth of function and complexity in the realm of life. Many of the basic solutions are retained from prokaryotes to humans: for example, the genetic code, and ATP synthase, and a lot of other things. But a lot of new or different solutions have been engineered in the course of time. That's why I have never agreed with those who think that the big problem is OOL, and the rest is just a minor issue. That's not true, not at all. Yes, OOL is a big problem. A very big one. But so it is the appearance of eukaryotes, and of multicellular life. And of each single phylum and body plan. And, in the end, of each single new functional protein, or of any single new complex re-engineering of an existing functional protein. Each of those things is really beyond the resources of any non design system in the whole universe. Each and all of them are designed. Design is an universal, constant process that manifests throughout the whole history of life on our planet (and maybe elsewhere).gpuccio
July 21, 2018
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gpuccio and DATCG @ 98: DATCG: “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.” gpuccio: Why shouldn’t they? DATCG: “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.” gpuccio responded:
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 [plan] is completely different. [emphasis added]
Do you have any thoughts about the on-going work that is being done on choanoflagellates? They are seen as a transitional form from single cell to multi-celled eukaryota because for some reason they have inter-cellular signaling proteins. (Why would a single cell eukaryote need inter-cellular signaling proteins?) Evidence of evolution for sure. But does this support blind watchmaker Darwinian evolution or is it evidence of guided and directed (designed) evolution. See my comments 8 and 13 on this thread: https://uncommondescent.com/intelligent-design/at-science-maybe-the-transition-from-single-cells-to-multicellular-life-wasnt-that-hard/#comment-661859john_a_designer
July 21, 2018
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PeterA: Thank you for your comments! :) "Y’all are making me dizzy with so much interesting information being thrown in your comments. How do you get all those papers so fast?" Pubmed, search engine and common sense, I suppose. :) "From what you guys are saying the field of NC RNA appears growing out of control, though ironically that stuff seems related to controls!" Absolutely! These are really exciting news, especially for us IDists. "BTW, I see that you’re having fun with all this." And a lot of it! "However, there may be some folks out there who aren’t enjoying this." Life is about personal choices... :)gpuccio
July 21, 2018
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Wow! Y’all are making me dizzy with so much interesting information being thrown in your comments. How do you get all those papers so fast? From what you guys are saying the field of NC RNA appears growing out of control, though ironically that stuff seems related to controls! BTW, I see that you’re having fun with all this. However, there may be some folks out there who aren’t enjoying this.PeterA
July 21, 2018
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DATCG: Ah, Cyrano and enlarged nasal placodes! I get it! :) I blasted the zebrafish sequence against homo sapiens, and indeed I found only the almost perfect conservation of a 66 nt sequence (56/66 identities), and nothing else out of 4630 nt in zebrafish and 9027 in humans. As described in your link: "Long terminal exon shows a number of conserved sequences within tetrapods. One ~300nt highly conserved sequence contains a 67 nt sequence conserved between tetrapods and zebrafish, a 26nt subregion of which is almost perfectly conserved in vertebrates and is hypothesised to be a miR-7 binding site." And yet: "Has similar structural characteristics in different vertebrate species." It seems that structural conservation works rather differently in RNAs than in proteins!gpuccio
July 21, 2018
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Ha! @145 Gpuccio! You're having to much fun! :) And apparently so are the scientist with their naming conventions! ;-) Inspirational as it is... http://lncrnadb.com/cyrano/ "... enlarged nasal placodes" heh! https://www.mirror.co.uk/news/uk-news/four-genes-determine-you-nose-8007124 The nose knows! ;-)DATCG
July 21, 2018
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DATCG, OLV: As I said, testis and brain: Forging our understanding of lncRNAs in the brain. https://www.ncbi.nlm.nih.gov/pubmed/29079882
Abstract During both development and adulthood, the human brain expresses many thousands of long noncoding RNAs (lncRNAs), and aberrant lncRNA expression has been associated with a wide range of neurological diseases. Although the biological significance of most lncRNAs remains to be discovered, it is now clear that certain lncRNAs carry out important functions in neurodevelopment, neural cell function, and perhaps even diseases of the human brain. Given the relatively inclusive definition of lncRNAs-transcripts longer than 200 nucleotides with essentially no protein coding potential-this class of noncoding transcript is both large and very diverse. Furthermore, emerging data indicate that lncRNA genes can act via multiple, non-mutually exclusive molecular mechanisms, and specific functions are difficult to predict from lncRNA expression or sequence alone. Thus, the different experimental approaches used to explore the role of a lncRNA might each shed light upon distinct facets of its overall molecular mechanism, and combining multiple approaches may be necessary to fully illuminate the function of any particular lncRNA. To understand how lncRNAs affect brain development and neurological disease, in vivo studies of lncRNA function are required. Thus, in this review, we focus our discussion upon a small set of neural lncRNAs that have been experimentally manipulated in mice. Together, these examples illustrate how studies of individual lncRNAs using multiple experimental approaches can help reveal the richness and complexity of lncRNA function in both neurodevelopment and diseases of the brain.
gpuccio
July 20, 2018
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DATCG, OLV: Another interesting features of lncRNAs seems to be: the names we give them! :) The lncRNA male-specific abdominal plays a critical role in Drosophila accessory gland development and male fertility. https://www.ncbi.nlm.nih.gov/pubmed/30011265 Parentally inherited long non-coding RNA Cyrano is involved in zebrafish neurodevelopment. https://www.ncbi.nlm.nih.gov/pubmed/30011017 Male-specific abdominal? Cyrano? !!!! :)gpuccio
July 20, 2018
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DATCG, OLV: In the testis: Profiling of testis-specific long noncoding RNAs in mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048885/
Abstract: Background Spermatogenesis, which is the complex and highly regulated process of producing haploid spermatozoa, involves testis-specific transcripts. Recent studies have discovered that long noncoding RNAs (lncRNAs) are novel regulatory molecules that play important roles in various biological processes. However, there has been no report on the comprehensive identification of testis-specific lncRNAs in mice. Results We performed microarray analysis of transcripts from mouse brain, heart, kidney, liver and testis. We found that testis harbored the highest proportion of tissue-specific lncRNAs (11%; 1607 of 14,256). Testis also harbored the largest number of tissue-specific mRNAs among the examined tissues, but the proportion was lower than that of lncRNAs (7%; 1090 of 16,587). We categorized the testis-specific lncRNAs and found that a large portion corresponded to long intergenic ncRNAs (lincRNAs). Genomic analysis identified 250 protein-coding genes located near (? 10 kb) 194 of the loci encoding testis-specific lincRNAs. Gene ontology (GO) analysis showed that these protein-coding genes were enriched for transcriptional regulation-related terms. Analysis of male germ cell-related cell lines (F9, GC-1 and GC-2) revealed that some of the testis-specific lncRNAs were expressed in each of these cell lines. Finally, we arbitrarily selected 26 testis-specific lncRNAs and performed in vitro expression analysis. Our results revealed that all of them were expressed exclusively in the testis, and 23 of the 26 showed germ cell-specific expression. Conclusion This study provides a catalog of testis-specific lncRNAs and a basis for future investigation of the lncRNAs involved in spermatogenesis and testicular functions.
Emphasis mine. This is very important. Testis and brain are always the pinnacle of functional specificity. The evidence for the fundamental role of lncRNAs is growing amazingly.gpuccio
July 20, 2018
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DATCG: And the field seems to rapidly expand: New and Prospective Roles for lncRNAs in Organelle Formation and Function. https://www.ncbi.nlm.nih.gov/pubmed/30017312
Abstract The observation that long noncoding RNAs (lncRNAs) represent the majority of transcripts in humans has led to a rapid increase in interest and study. Most of this interest has focused on their roles in the nucleus. However, increasing evidence is beginning to reveal even more functions outside the nucleus, and even outside cells. Many of these roles are mediated by newly discovered properties, including the ability of lncRNAs to interact with lipids, membranes, and disordered protein domains, and to form differentially soluble RNA-protein sub-organelles. This review explores the possibilities enabled by these new properties and abilities, such as likely roles in exosome formation and function.
Emphasis mine.gpuccio
July 20, 2018
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DATCG: This is a "pearl": Regulation of IL-17 by lncRNA of IRF-2 in the pearl oyster. https://www.ncbi.nlm.nih.gov/pubmed/30017925
Abstract Long noncoding RNAs (lncRNAs), once thought to be nonfunctional, have recently been shown to participate in the multilevel regulation of transcriptional, posttranscriptional and epigenetic modifications and to play important roles in various biological processes, including immune responses. However, the expression and roles of lncRNAs in invertebrates, especially nonmodel organisms, remain poorly understood. In this study, by comparing a transcriptome to the PfIRF-2 genomic structure, we identified lncIRF-2 in the PfIRF-2 genomic intron. The results of the RNA interference (RNAi) and the nucleus grafting experiments indicated that PfIRF-2 might have a negative regulatory effect on lncIRF-2, and PfIRF-2 and lncIRF-2 may have a positive regulatory effect on PfIL-17. Additionally, lncIRF-2, PfIRF-2 and PfIL-17 were involved in responses to the nucleus graft. These results will enhance the knowledge of lncIRF-2, IRF-2, and IL-17 functions in both pearl oysters and other invertebrates.
Emphasis mine. Nice interaction between an intron and lncRNA.
According to the genomic distribution into one or more of the following five categories, sense, antisense, bidirectional, intronic and intergenic [29], lncIRF-2 belonged to intronic lncRNA. Meanwhile, the alignment of lncIRF-2 yielded no matches via the NCBI BlastN search, suggesting that lncIRF-2 was lowly conserved, like most of its lncRNA counterparts that were not conserved. ... This study explored the correlation of lncIRF-2 and PfIRF-2 and their regulation on PfIL-17. In addition, it has been shown that lncIRF-2 could be functional, not just transcriptional ‘noise’.
Emphasis mine. So, a functional lncRNA which derives from an intron and is "lowly conserved", IOWs highly species specific. It's becoming a very strong trend, I would say. :)gpuccio
July 20, 2018
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Thanks to DATCG and gpuccio for maintaining such a high level of scientific excitement in this discussion. Excellent work.OLV
July 20, 2018
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DATCG: Great contributions, as usual! :) There can be no doubt about the modularity of biological design: it's OOP all the way! I agree that bio-engineers are badly needed. Bio-informaticians, who usually have a mixed education, will certainly help a lot. The mechanisms of the Fanconi complex are specially intriguing. Repairing DNA is certainly a delicate task. I like very much this passage from the paper you quoted:
The E3 ligase activity of this reaction resides in the FA core complex consisting of seven FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, and FANCL) and two FA-associated proteins (FAAP20 and FAAP100), with the RING domain protein FANCL bearing the E3 ligase activity (Alpi et al., 2008; Meetei et al., 2003). Aside from FANCL and FAAP20, most other components of the core complex have neither recognizable motifs nor clearly defined functions as to how they contribute to the DNA damage-mediated FANCD2/I monoubiquitination.
Emphasis mine. That's what happens as soon as we enter the vastly misunderstood field of function regulation: the usual concepts of protein domains, functional conservation and "easily" recognizable function just disappear. And we are left with extremely complexd and highly functional multi-structures where we cannot recognize anything easily understandable. The same is true, IMO, for non coding DNA. There are functions that we understand, and functions that we still don't understand at all. Most regulatory functions are in the second group.gpuccio
July 20, 2018
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So going offtopic a bit, but I consider TEs module components and essentially genetic code as a modular system of component parts. So from TEs to larger molecules, modularity is key... During a quick search, as I was posting #138, found this gem from 2015 on the E3-Ligase and Fanconi Anemia(FA) Core Complex. I'll cross post it as well on Ubiquitin post. Modularized Functions of the Fanconi Anemia Core Complex Summary
The Fanconi anemia (FA) core complex provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. Of the seven FA gene products forming the core complex, FANCL possesses a RING domain with demonstrated E3 ligase activity. The other six components do not have clearly defined roles. Through epistasis analyses, we identify three functional modules in the FA core complex: a catalytic module consisting of FANCL, FANCB, and FAAP100 is absolutely required for the E3 ligase function, and the FANCAFANCG-FAAP20 and the FANCC-FANCE-FANCF modules provide nonredundant and ancillary functions that help the catalytic module bind chromatin or sites of DNA damage. Disruption of the catalytic module causes complete loss of the core complex function, whereas loss of any ancillary module component does not. Our work reveals the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex
Discussion
Through creation of isogenic single and double mutants of the FA genes, we came to the unexpected finding that not all the components of the core complex contribute equally to cellular resistance against DNA damage. This observation deviates from a general paradigm that losing any one of the core FA proteins leads to complete elimination of FANCD2 activation and disintegration of the core complex. Instead, our results suggest that different functional modules exist in the core and that the overall integrity of the core complex is sustained when certain FA proteins are removed.
This points to Design. Elimination of specific modules did not cause a problem in this case for a specific item of research. Allowing continued specific processing of the molecule for their research. Prediction? Researchers will find errors or inoperative function(s) in other programming aspects maybe yet unknown upon removal of the specific modules. If so, this adds to the modularity principle of Design Concepts. Merely removing or eliminating code can only eliminate specific areas of performance, while allowing performance for the other modules to remain. Thus the advantages of modular programming are not only efficiency of coding, but of survival. If this was not a modular process, function would cease. Unguided events cannot anticipate such damage or requirements of modularity. Only Designers can.
Our work establishes a modularized functional assembly of the FA core complex consisting of a catalytic module and two modules with nonredundant functions in the chromatin recruitment of the core complex. The coordinated actions of these three modules enable the E3 ligase activity to be localized to the sites of DNA damage and carry out the spatially defined FANCD2/I monoubiquitination with maximum efficiency to counter DNA damage. The catalytic core module is the most critical component functionally, as reflected by the most severe phenotypes of the FANCL and FANCB mutants. The existence of a catalytical core module within the FA core complex is further supported by biochemical evidence from Rajendra et al. (2014)
Modular Programming increases efficiency and depends upon short, fast reads of easily recognizable sequences of pre-Coded Elements like the TE's in this post, or Tagging by Ubiqutin for Repair Processing designation or degradation and recycling of parts.DATCG
July 19, 2018
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Here's another paper recently on "noncoding regulatory elements" that contribute to new phenotypes and "Accelerated Evolution." PDF document at Cell.com... Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance Note in the paper it mentions E3-Ligases. Will cross-post in your Ubiqutin article Gpuccio. Summary:
The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering 33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.
Interesting! Ubiquitin is not mentioned, but is in play at work with E3 Ligase. Keeping in mind that "elements" are information packets that can be read for processing. Continuing on...
New phenotypes frequently arise due to evolutionary changes to "noncoding" regulatory elements rather than protein-coding changes (Carroll, 2008; Wray, 2007). Although much of the genome is biochemically active (ENCODE Project Consortium, 2012), identifying functional elements for particular traits is challenging, and the best approaches are debated (Kellis et al., 2014). One approach is to focus on conserved genomic regions. Indeed, species-specific changes to conserved noncoding elements are linked to some major phenotypic effects, such as the loss of limbs in the snake (Kaltcheva and Lewandoski, 2016; Kvon et al., 2016) and the loss of penile spines in humans (McLean et al., 2011). Conserved elements exhibiting accelerated evolution in a particular species may have roles in shaping the traits of that species (Bird et al., 2007; Boyd et al., 2015; Capra et al., 2013; Hubisz et al., 2011; Kim and Pritchard, 2007; Lindblad-Toh et al., 2011; Pollard et al., 2006a, 2006b, 2010; Prabhakar et al., 2006). Accelerated regions (ARs) are best known from studies of human ARs and are conserved elements with significantly increased nucleotide substitution rates due to the effects of positive selection, relaxed purifying selection, or GC-biased gene conversion in a particular lineage (Hubisz and Pollard, 2014; Kostka et al., 2012; Pollard et al., 2010). For example, one human AR is an enhancer with putative roles in the evolution of the human thumb (Prabhakar et al., 2008). Despite these advances, the identity and roles of most functional elements in the mammalian genome remain unclear.
"noncoded" above emphasis mine And following discussion...
Discussion DISCUSSION Our study tested whether a comparative analysis of ARs in species with distinctive traits facilitates the discovery of candidate functional elements for the overt and clinically relevant traits exhibited by these species. From elephant, Hib bat, orca, dolphin, mole rat, and squirrel ARs, we identified a set of 33,283 candidate elements (7% of mammalian conserved regions tested). Multiple lines of evidence support the functionality of these elements, including selective constraint (conservation) from wallaby to human, regulatory protein binding in humans and mice, and evidence for accelerated evolution in specific lineages.
DATCG
July 19, 2018
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Gpuccio @122, Interesting! A quick search on the paper shows three authors. One, Yang-Yang Jiang, is from the Institute of Process Engineering. That's all the info I could find on that one particular author. Assumption - Jiang is an engineer. Maybe a general process engineer. Or, maybe specialized with a background in chemical and/or biotechnical expertise, or industrial processing and software design of processes. Why does research in this field require a "Process Engineer?" if this is all unguided, blind evolution? Because they're recognizing the need to reverse engineer an "unguided process?" I'm aware many universities have expanded their programs to include engineering hard sciences in the field of molecular biology and genetics. That's great. It's the only way they will eventually reverse engineer the code(s) of life. I wonder if the Chinese are taking a more practical approach to reverse engineering since they're not tied down by western past of Darwinian worship? "... required" is key...
A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). Moreover, it has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are not only expressed but required for pluripotency in human embryonic stem cells (hESCs).
Hmmmm, remember that evolutionist in the past thought these transposable elements to be ancestral vestiges of viruses? If by design however, they'd be modular components, recognized by the system code(s). Would an unguided, uncoded, blind "unprocess" be able to recognize a modular component insert? How? By deception as a virus? Hmmmm... I wonder if extrapolation of beliefs and assumptions on bacteria leads to possible misconceptions farther up a long series and chain of events? There always seems to be a lot of contortion in Darwinism and twisting to fit in preconceived assumptions. Again, just speculation. But if by Design, modularity is key for component processing, easily recognizable inserts adjust and radiate through the different phyla. So, it's not a virus, but a Designed system of rapid radiation of information. This might explain such events as the Cambrian.DATCG
July 19, 2018
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DATCG, OLV, PeterA: In primates: Conserved expression of transposon-derived non-coding transcripts in primate stem cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331655/
Abstract BACKGROUND: A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). Moreover, it has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are not only expressed but required for pluripotency in human embryonic stem cells (hESCs). RESULTS: To identify additional TE-derived functional non-coding transcripts, we generated RNA-seq data from induced pluripotent stem cells (iPSCs) of four primate species (human, chimpanzee, gorilla, and rhesus) and searched for transcripts whose expression was conserved. We observed that about 30% of TE instances expressed in human iPSCs had orthologous TE instances that were also expressed in chimpanzee and gorilla. Notably, our analysis revealed a number of repeat families with highly conserved expression profiles including HERVH but also MER53, which is known to be the source of a placental-specific family of microRNAs (miRNAs). We also identified a number of repeat families from all classes of TEs, including MLT1-type and Tigger families, that contributed a significant amount of sequence to primate lncRNAs whose expression was conserved. CONCLUSIONS: Together, these results describe TE families and TE-derived lncRNAs whose conserved expression patterns can be used to identify what are likely functional TE-derived non-coding transcripts in primate iPSCs.
gpuccio
July 18, 2018
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PeterA: I knew you were a fan of Popper! :)gpuccio
July 18, 2018
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