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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
PaV: Always a pleasure to hear from you! :) I think that we still understand very little about the functions of TEs. My personal idea is that they have two completely different kinds of functions: a) By their guided retrotransposition activity in genomes they can slowly implement genomic changes in the course of evolutionary history. IOWs, they can be very important design tools. The scientific literature is rather abundant about the role of TEs in promoting new genes, new regulations and so on in the course of natural history. Luckily, TEs almost always leave specific signatures that can be recognized, for example when they build new genes from non coding DNA, or when they silence genes creating pseusogenes, sometimes functional pseudogenes. Of course, neo-darwinists consider that evidence as random emergence of function, as they always do. But I think we know better! :) b) Then there is the possible regulatory roles of TEs as they are in a specific species, IOWs their functions which are independent from retrotransposition. those functions that, according to Larry Moran, should not exists, and that are instead the subject of the paper you discovered. I think we really know very little about those functions. The quoted paper is probably one of the most detailed about that issue, and it strongly suggests that many functions are implmented by TE RNA, IOWs by the transcriptional outcome of genomic TEs. Tis is a fascinating field, but I believe that we have to wait for more data to get some general idea. TEs and their sequence and spatial organization can potentially influence nuclear regulation in many ways: 1) They make up a big part of the genome, so their spatial disposition can certainly have a major role in determining the complex functional regulation of chromatin states. 2) Transcribed RNA including TEs, as suggested by the quoted paper, can have a lot of complex regulatory interaction with all kinds of nuclear processes. We know that non coding RNAs are abundant, important and complex. And we don't understand well their many functions. We know a few things, for example that those functions are probably more related to their structure than to their strict sequence, which could explain why they are in general less conserved than proteins, even if functional. And we know specific examples of specific regulations. TE containing RNAs are really a new aspect, which has been widely ignored in the past years, and is now beginning to gain attention. There are many reasons for that scarce attention to the problem in scientific literature: some of them are technical (those RNAs are difficult to study) and others are ideological (brilliant neo-darwinists have already decided that they are junk). I would suggest the following, very interesting paper: Stable C0T-1 Repeat RNA Is Abundant and Is Associated with Euchromatic Interphase Chromosomes https://www.cell.com/cell/fulltext/S0092-8674(14)00135-4
Recent studies recognize a vast diversity of noncoding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated) DNA probes detects surprisingly abundant euchromatin-associated RNA comprised predominantly of repeat sequences (C0T-1 RNA), including LINE-1. C0T-1-hybridizing RNA strictly localizes to the interphase chromosome territory in cis and remains stably associated with the chromosome territory following prolonged transcriptional inhibition. The C0T-1 RNA territory resists mechanical disruption and fractionates with the nonchromatin scaffold but can be experimentally released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds to aberrant chromatin distribution and condensation. C0T-1 RNA has several properties similar to XIST chromosomal RNA but is excluded from chromatin condensed by XIST. These findings impact two “black boxes” of genome science: the poorly understood diversity of noncoding RNA and the unexplained abundance of repetitive elements.
From what I have read, I would think that one of the main ways that TE RNAs can have important regulatory roles is by interacting, in different and complex ways, with chromatin dynamic architecture, both directly and thorugh interaction with other players. They could certainly be involved in fidelity in translation, as you suggest, but I cannot offer at present any special support for that kind of role, as far as I know. Have you any data about that?gpuccio
June 23, 2018
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Mung: I will see what I can do. The problem is that the comments are spread on many pages, so you cannot just do a search in the whole thread, or at least I suppose so. "The main complaint seems to be that you can’t rule out “evolutiondidit” and expect evolutionists to show that it can. They expect you to show that evolution can’t. Then they accuse you of asking THEM to prove a negative." That I have answered many times, and I don't want to repeat always the same things. That would be more repetitive than a transposon! :)gpuccio
June 23, 2018
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gpuccio:
...and now I am a little discouraged at the perspective of going thorugh 939 comments!
It should be easy to see which ones are by Joe though. As the author of the OP his posts in the thread have a special coloring to them. The main complaint seems to be that you can't rule out "evolutiondidit" and expect evolutionists to show that it can. They expect you to show that evolution can't. Then they accuse you of asking THEM to prove a negative.Mung
June 23, 2018
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gpuccio: Thank you for the information you've given us. What you've posted makes for a better understanding of these multiple LINE elements and the possible role they play. The thought that strikes me is that perhaps these LINE elements play some kind of role in preserving the fidelity of protein transcripts prior to subsequent translation--IOW, the transcribed mRNA from one such genomic unit containing a LINE is first 'compared' to the LINE element itself prior to translation in the ribosome. It would make sense that this would occur early on in embryonic activity where 'fidelity' in translation would likely be very critical for overall development. I would hope you could comment on this thought.PaV
June 23, 2018
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bill and gpuccio- It is very telling that neither Joe Felsenstein nor any other TSZ contributor has provided any evidence that blind and mindless processes can produce any genes that code for proteins. They can only hoot and whine about 500 bits of functional information. It is really sad to see that such pathetic people still exist.ET
June 23, 2018
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bill cole: Yes, highly specific regulators are often confined to specific cells or states. Only housekeeping genes are ubiquitously expressed. Yes, I have seen the OP by Joe Felsestein at TSZ, and I have answered it in some detail here: 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/ Comments #394, 395, 397, 400, 403, 406, 407, 408. At that point, he had not yet answered my new comments. Frankly, I have not followed the thread after that, and now I am a little discouraged at the perspective of going thorugh 939 comments! Are you aware of some more recent comment by Joe Felsestein about my comments on his OP? I would be specially interested in any comment from him about my "thief" thought experiment, which was specifically addressed to him. He has not addressed that specific issue in his OP about my thoughts, and yet I believe that the thief experiment is extremely pertinent and clarifying to the discussion about functional complexity. So, I was really disappointed that he did not address it in his OP.gpuccio
June 23, 2018
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Amblyrhynchus (and PaV): I think you are making a very basic error. The different copies of a transposable element are not identical. Not at all. They can of course be recognized as members of a specific family of retrotransposons, in this case L1, but they are different. See for example here: High Levels of Sequence Diversity in the 5' UTRs of Human-Specific L1 Elements https://www.hindawi.com/journals/ijg/2012/129416/
Approximately 80 long interspersed element (LINE-1 or L1) copies are able to retrotranspose actively in the human genome, and these are termed retrotransposition-competent L1s. The 5? untranslated region (UTR) of the human-specific L1 contains an internal promoter and several transcription factor binding sites. To better understand the effect of the L1 5? UTR on the evolution of human-specific L1s, we examined this population of elements, focusing on the sequence diversity and accumulated substitutions within their 5? UTRs. Using network analysis, we estimated the age of each L1 component (the 5? UTR, ORF1, ORF2, and 3? UTR). Through the comparison of the L1 components based on their estimated ages, we found that the 5? UTR of human-specific L1s accumulates mutations at a faster rate than the other components. To further investigate the L1 5? UTR, we examined the substitution frequency per nucleotide position among them. The results showed that the L1 5? UTRs shared relatively conserved transcription factor binding sites, despite their high sequence diversity. Thus, we suggest that the high level of sequence diversity in the 5? UTRs could be one of the factors controlling the number of retrotransposition-competent L1s in the human genome during the evolutionary battle between L1s and their host genomes.
Not only they are different in sequence, they are of course different in their specific positions in the genome, due to the more or less ancient retrotransposition activity during evolution. Moreover, the functional role described in the paper referenced in the OP is implemented by LINE 1 RNA, and is a role linked to RNA structure. The functional structure of that RNA can vary a lot according to the way different basic "modules" (in this case, L1 elements), which are however significantly different one from the other, are transcribed. IOWs, TEs are not at all identical and repetitive modules, where all the information is already implemented in one copy. The opposite is true: TEs are highly different modules that can build highly different complex combinatorial structures, for example at the RNA level. So, the relevant information is not in the original prototype of the module, but rather in the variation in the individual modules and in their different combinations. Therefore, your argument is completely out of order.gpuccio
June 23, 2018
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Ribosomal RNA can make up ~80% of a cell's RNA, but we manage to get by with a couple of hundred copies of the DNA that. I don't think we need 800,000 copies of L1. LINEs are elements that can copy themselves. When the 798,981st copy fixed in the human genome do you think it did so because 798,980 just wasn't enough, and one more was going to make a difference. Or was it maybe because one more copy makes no difference so nothing prevented one more copy accumulating in the genome.Amblyrhynchus
June 23, 2018
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Ambly: The study's authors have talked about the importance of there being an abudance of this tanscript, and that this abudance of copies helps assure having a faithful copy, but also of providing numerous opportunities for mutation, if needed. It's interesting that when IDers point out that 'copied' information isn't "new" information, this is not accepted by Darwinists who claim that this is, indeed, "new" information. But now that there are thousands of copies which are deemed useful to an organism, we're told that this is nothing more than just a 'copy' of ONE element. Very interesting. In the case of 800,000 copiesof LINE1, the actual numbers of the element are seen as being needed. IOW, copies here are important. However, in the case of 'information,' obviously a 'copy' is not an advance in what normal people consider information to be. An example: at a high school, there might be 100 copies of a biology book; but the teacher, at home, only needs ONE copy. Very different circumstances. The more principled view of these matters rests with the ID community.PaV
June 23, 2018
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LINE1, which makes up 24% of the genome is NOT “junk,” but an essential part of embryonic development.
There are ~800,000 copies of L1 in the human genome. To make L1 RNA you need... one. Not sure you can put the whole of that 24% into the non-junk category just yet.Amblyrhynchus
June 22, 2018
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gpuccio
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.
I once asked Larry if the low level of transcription he was measuring was during embryo development. He was not making measurements at this stage and I think this probably where most the activity. BTW: Have you seen the post Joe dedicated to you at TSZ? I starting doing blasts of proteins I had previously studied and found one that is 99%+ identical between humans and a finch specie. 200 million years of almost perfect preservation. 780 AA long :-)bill cole
June 22, 2018
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PaV: As a further answer to Larry Moran, always from the paper you found: "Our results indicate that chromatin-associated LINE1 RNA regulates gene expression and developmental potency without requiring retrotransposition activity." IOWs, it's true, like Moran says, that many of our transposons are "defective", in the sense of having lost retrotransposition activity, but that seems not to prevent them from being functional, in a very refined way! Indeed, losing retrotransposition activity could be an important functional development. Again from the paper: "This role of LINE1 as a chromatin-associated RNA therefore avoids the potential detrimental effects of LINE1 retrotransposition that have been reported in several disease states, including cancer"gpuccio
June 22, 2018
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This is very interesting! So, transposons are not only the most likely design tool in shaping novelties in genome evolution, as I have always argued: they are also important regulators of development. :) This is the very interesting conclusion of the paper:
The interaction of LINE1 RNA with binding partners, such as Nucleolin is expected to be mediated by RNA secondary structure, which is less constrained by primary sequence than protein-coding regions. Thus, rather than being a vulnerability, the regulation of early development by TEs may allow both robustness, due to the repeated nature of TEs, and adaptability, due to their rapid evolution and their potential to support transposition in conditions of stress. In this regard, it is interesting that the percentage of the genome occupied by LINE1 elements seems to have sharply increased with development of therian mammals (e.g., Ivancevic et al. [2017]). The exploration of the function of LINE1 in other species should shed light on the role of TEs in shaping the evolution of development.
Transposons are definitely the future. Thanks to PaV for finding this and to Denyse for reporting it. :)gpuccio
June 22, 2018
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The following is from Sandwalk. Larry Moran wrote this just this past February:
So far, so good. I disagree with their description of the rest of the genome. They imply that most of it is selfish DNA composed of transposons like Alu's and LINE-1 sequences. I wish they had put more emphasis on the fact that much of our genome consists of defective transposons and viruses that are junk, plain and simple. They aren't selfish DNA today, although they once were in the past.
As I mentioned to Denyse: lots of egg on their face. And it will ONLY get worse.PaV
June 22, 2018
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