Larry Moran, Dan Graur and other garbologists (promoters of the junkDNA perspective), have argued SINES and ALU elements are non-functional junk. That claim may have been a quasi-defensible position a decade ago, but real science marches forward. Dan Graur can only whine and complain about the hundreds of millions of dollars spent at the NIH and elsewhere that now strengthens his unwitting claim in 2013, “If ENCODE is right, Evolution is wrong.”
Larry said in Junk in Your Genome: SINES
In humans, the largest family of SINEs is called Alu elements after the fact that the sequence is cleaved by the restriction endonuclease Alu. These SINEs are also derived from 7SL RNA but the rearrangement is different from that in mouse. (They have a common ancestor.) There are about one million Alu elements in the human genome.
SINEs make up about 13% of the human genome. The largest proportion, by far, is Alu elements but there are small numbers of SINEs derived from other cellular RNAs such as the U RNAs required for splicing and snoRNAs (Garcia-Perez et al. 2007).
SINEs are parasites (selfish DNA). They are not essential for human survival and reproduction, especially the huge majority of SINEs that are defective. Thus, at least 13% of the human genome is clearly junk. The total amount of junk DNA contributed by all transposable elements is 44% of the genome (Kidwell 2005).
Thursday, February 07, 2008
Where to begin? First off, Larry’s claim was made over 8 years ago. Larry ran the risk of becoming the butt of jokes since a scientific discovery here and there could overturn his precarious claims.
Below is a video associated with a 2015 paper from National Academy of Sciences, a mere 7 years after Larry’s claim was made. One important aspect of SINES are the CTFC binding site motifs often found in SINEs. The motifs can’t be randomly located, otherwise they would not properly create functional chromatin extrusion loops. Further, these CTFC binding site motifs must be coordinated to “point” in the right direction many base pairs away in order for these extrusion loops to form. See this amazing video of extrusion loops and CTFC binding sites (which are often found in SINES):
CTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution [sic]. To gain insight into how these DNA elements are conserved and spread through the genome, we defined the full spectrum of CTCF-binding sites, including a 33/34-mer motif, and identified over five thousand highly conserved, robust, and tissue-independent CTCF-binding locations by comparing ChIP-seq data from six mammals. Our data indicate that activation of retroelements has produced species-specific expansions of CTCF binding in rodents, dogs, and opossum, which often functionally serve as chromatin and transcriptional insulators.
…
We therefore searched for an alternative mechanism for the de novo creation in a common mammalian ancestor of the thousands of CTCF-binding events now found throughout mammals. Despite the generally high conservation of CTCF motif-word usage, we noted that specific sets of motif-words were overrepresented in rodents (mouse and rat), dog, and opossum (Figure 4A). We found that the vast majority of these overrepresented motif-words are embedded within SINE transposons (Figures 4B and andS4S4).
The following 2015 paper lists many roles of ALU elements, about 7 years after Larry’s claims about ALUs were vomited onto the internet. Will he feel as confident now about his claims or will retractions be forthcoming?
The role of Alu elements in the cis-regulation of RNA processing
Alu elements are an important engine for functional diversity within the primate transcriptome. As building blocks of extra genetic material, retroelements are used to invent new ways to vary mRNA. The almost 300 nt long Alu element is an ideal player for several reasons: (1) Alus are frequently inserted into non-coding regions of pre-mRNAs, (2) when transcribed, they easily form stable secondary structures that seed a number of different RNA processing events, and (3) small changes to their sequence make them targets for a number of RNA-binding proteins that regulate gene expression. Depending on its location and specific sequence, the Alu element can induce different RNA processing events (Fig. 5). If two inverted Alus reside on each side of an exon, they can form a double-stranded RNA structure that may induce back-splicing and the formation of circular RNA. An intronic Alu with a mutated or edited sequence can induce alternative splicing or Alu exonization. Inverted repeat elements can also contribute to transcript variations in a more fine-tuned manner by inducing A-to-I editing within coding sequence. Also, Alus in introns and 3′UTRs can provide both miRNAs and their target sequences. In this review, we have only highlighted a few examples of how Alu elements may contribute to transcriptome variation in primates. These effects certainly combine with the better explored genomic variations that Alus create. Future studies will most likely reveal additional mechanisms on how these elements modulate our genetics.
Here is an example from that paper:
Possible Alu-induced RNA processing events. a Inverted Alus on each side of an exon that form a dsRNA structure may induce exonic RNA circularization. b An intronic Alu with a mutated or edited sequence can induce alternative splicing and/or Alu exonization. c Inverted Alu elements forming a dsRNA structure frequently induce A-to-I editing at nearby sites. d Within introns Alus can contribute to maturation of miRNAs. eAlu elements in 3′UTRs may act as miRNA targets
Why would anyone want to seriously ‘talk science’ with you when you’ve shown exactly what you think of ‘science’ over the years?
There are a few crows around here that appear to be experienced garbologists.
Something to note in a forgotten article by evolutionary biologist Richard Sternberg. It will take two comments to show his point. So this comment is the first part…
This figure below is from this freely available paper:
http://www.nature.com/nature/journal/v428/n6982/full/nature02426.html#f12
The figure shows the sequence divergence of various classes of SINES:
Part 2 of the comment stream started previously. Sternberg references the diagram below.
http://www.evolutionnews.org/2010/03/beginning_to_decipher_the_sine032981.html
From this paper, at around 3/4 are in genes in the introns, and introns are part of genes.
and
Introns aren’t exons, DNA_Jock. 🙄
Additionally, from:
http://rnajournal.cshlp.org/content/19/5/591.abstract
Shazam!
Despite this:
Don’t equate plugging your ears and closing your eyes as the same thing as absence of evidence. I cited several papers providing reasonable evidence of function. The fact that doesn’t count as evidence for you doesn’t mean it should not count as evidence for everyone else.
Said the guy who does exactly that.
stcordova,
SINEs may differentially accumulate in gene rich regions because they are the regions most accessible to their mode of action. It’s harder to transpose into heterochromatin. But no, evolutionary theories, mechanistic constraints, loadabollocks, lalalalala.
Introns part of genes? Hmmmm. Depends, really.
Oh, Sal,
My “exons” question was a test, to see if you actually read and understand the papers that you cite. You failed.
But you are getting there, Sal, albeit very slowly.
Here’s an easier question:
Of the million Alus, how many intronic inverted pairs are there?
There’s a guy in Australia who picked up a multi-pound chunk of nearly pure gold.
Proof that not all the earth’s surface is devoid of large chunks of gold.
Kind of funny hearing that from the guy who could not comprehend that 100 million editiable sites implies more potentially functional genomic sites than the pathetic 0.1% you said were potentially functional in Alus.
DNA_jock’s math:
The lack of understanding is yours since a large fraction Alus, around 3/4, is in the introns, not exons. Cold spring harbor reports 100 million editable sites mostly in Alus generated RNA transcripts. I cited the report here:
I knew about the Cold Spring Harbor paper, because I looked up some of the references in the papers cited in the OP. Pretty sharp of me, eh?
Here is a math lesson for you DNA_jock.
There are around 3.3 gigabase pairs in the genome, or 6.6 gigabases (counting both strands). If 100 million DNA sites transcribe to 100 million RNA sites that are editable, that implies 100 million RNA editable sites that can be generated by 100 million DNA sites. (since A is editable, but T on the other strand is not, 100 million DNA base pair positions transcribe to only 100 million A-to-I editable RNA positions, not 200 million A-to-I editable RNA positions).
100 million / 6.6 giga bases ~= 1.5%.
Do you need lessons on how to use a calculator, because 1.5% is a lot bigger than your 0.1% figure. I derived the 1.5% figure by taking the figures in the papers I cited, you asserted the 0.1% figure because you were obsessed with Alus in exons rather than realizing Alus could be functional while residing outside of exons.. In other words you got caught pulling figures out of your fuzzy misunderstandings, just like you argue chromatin is a fuzzy concept.
After being caught, and offer a retraction and say, “Sal was right”, you spin spin spin.
Here’s a suggestion, before you pretend you actually are in a position to look down your nose at me, you might want to try comprehending
100 million/ 6.6 giga bases ~= 1.5%, not 0.1%.
Maybe you should change your handle to DNA_howler. Hahaha!
I imagine it’s hard to be YEC without selective interpretation.
LMAO
I objected to your claim
Asking you the question:
which question you have yet to even attempt to answer.
To make it easier for you, Sal, I asked you:
because those are the ones that your sources claim might be involved in RNA editing. And the number is available in the sentence following the one you quoted as your source of the 3/4 in introns number.
From Sal’s reference:
5009 x 300 x 2 (generously assuming that the entirety of both Alus is required, but not counting redundant pairs) = 3 million.
3 million / 3.3 billion = 0.1%
Your misplaced triumphalism makes me smile.
But these numbers are meaningless, until you can produce and defend an estimate for what proportion are in fact functional…
ETA: The CSHL count of “editable sites” is meaningless; by this standard, every base pair is potentially functional.
No, and that’s howler. You say that right after I cited a paper on intronic Alus, which refers to Alus within introns, not Alus within exons. Too funny. Here is it is.
https://www.researchgate.net/publication/23281933_Intronic_Alus_Influence_Alternative_Splicing
Gee, DNA_jock, did you not notice intron is spelled “INTRON” not “EXON”.
The papers I cited involved lots of intronic Alus not exonic ones — you know, the ones that are called “Intronic Alus” right there in the title of the paper you refuse to acknowledge. Boy talk about stubborn determination to remain in denial right when it is spelled out in the title of a paper I cited.
Contrast DNA_Jocks claim, with cold spring harbor laboratories (a respected organization):. He just embarrasses himself with his calculations.
The calculation is basically:
DNA_jock just pulled his numbers out of his one non-reading.
You have a problem with that? But the bases that are described as editable are those that are ADAR mediated edits not any possible edit, specifically edits on A’s. C,G, and T aren’t ADAR mediated A-to-I editable. You’d think someone with the handle “DNA_Jock” would understand A-to-I editable doesn’t mean C, G or T are A-to-I editable. Howler. That’s even more funny than you’re “chromatin is wonderfully fuzzy concept” claim.
Sure there could be other ways to edit the other bases, but those aren’t A-to-I edits. The most common RNA edit known so far is A-to-I edits.
Furthermore, other researchers actually did sequencing to specifically find that the Alu generated RNAs showed actual editing (not just potential editing) in ways they believed quite meaningful to brain function:
http://www.cell.com/trends/genetics/abstract/S0168-9525(04)00332-4?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168952504003324%3Fshowall%3Dtrue
So there is detectible actual A-to-I editing, not just potential editing (as you insinuate). Furthermore, as pointed out in another paper:
You don’t want to accept the opinions and findings that Alus are actually edited and therefore potentially functional, that’s up to you, but these authors have more credibility with me because they apparently know
Sal, you need to pay attention. That was worse than a quote mine. That was explicit contradiction of the actual words. Let’s go back to the source:
You should be able to see that he’s referring to intronic inverted pairs, not exons. The misplaced triumphalism is getting old.
The figure of 5009 used by DNA_jock for his miscalculation is for an ALU pair within the same intron, hence that’s why he gets a figure of 0.1% not 1.5%. He went into the usual incomprehensible mode so that when his opponent can’t understand his gibberish, he assumes his opponent knows nothing. Well, I know 1.5% isn’t equal to 0.1%. 🙂
When he got called on this discrepancy between his 0.1% and the Cold Spring Harbor figure of 1.5%, he finally revealed where he was pulling his numbers. Dumb! dsRNAs are not restricted to forming from the same intron, in fact some dsRNAs involve an ALU in an intron and one in and exon such as described in this paper:
http://www.nature.com/nbt/journal/v22/n8/full/nbt996.html
In fact the diagram this refers to shows :
(intronic ALU) + exon + intron + (inverted exonic ALU)
so that clearly is more than a pair of ALU inside an intron.
But the bottom line is DNA_jock ignored the 1.5% number right there in the paper.
So in regards to your comment:
Oh, you should be referring to DNA_jock, because I at least know 1.5% isn’t the same as 0.1%, which is more than I can say for DNA_jock.
If he kept getting 0.1% with his calculations, and cold spring harbor reported 1.5%, he was wrong in his understanding, and worse it was beneath him to acknowledge he couldn’t reconcile the problem.
105.7 million/ 6.6 giga bases ~= 1.5%, not 0.1%
You’re obviously missing something and so is DNA_jock.
Speak to yourself.
1.5% does not equal 0.1%.
I actually agree with Sal for a change.
As an aside, I discovered this:
sayeth the YEC.
DNA_Jock and John Harshman have some obsolete understanding of Alus.
From Lehninger Principels of Biochemistry sixth edition (as in like the last few years):
Besides, I know 1.5% isn’t the same as 0.1% I learned that even before high school!
DNA_Jock, try to learn some textbook stuff from textbooks that are more recent, and learn some basic math too, like the fact 1.5% doesn’t equal 0.1%. 🙂
Nothing of what you brainlessly quoted goes even one iota towards demonstrating that DNA_Jock or John Harshman have “an obsolete understanding of Alus”. And it doesn’t call the reality of common descent into question. At all.
Rumraket,
Well, I certainly know better than Francisco Ayala about Alus:
http://biologos.org/blogs/archive/on-reading-the-cells-signature/
Ayala needs to read up on the latest. Has he retracted his un-informed article? Nope.
Oh really?
Yes really. If Ayala, Ken Miller and Dennis Venema show up here I’ll set ’em straight on some of their errors.
stcordova,
Unwarranted arrogance is a symptom of Dunning-Kruger Syndrome. It isn’t very Christian either.
But warranted arrogance is very Christian.
Sal,
Why not publish a paper and set their errors in stone for all eternity?
Does that actually mean something, or is the network of in-jokes that makes it a multi level sneer only available to you, Mung?
Yes, and he’s willing to demonstrate it to a paid lay audience in a church basement.
Oh Sal,
My apologies for upsetting you again, but you really shouldn’t re-visit this thread, where you put on such a stellar display of wilful ignorance, and flagrant misunderstanding (introns/exons, anyone? LOL).
It’s really simple: a rather goofy paper from CSHL reckons that there are 100 million “editable” nucleotides in Alus. Cool story bro.
The question has always been (remember, the topic is junk DNA) what proportion of these editable sites have function.
So, until you come up with some evidence regarding this proportion, showing that it is above 6.7%, I’ll stick with my original ballpark estimate.
More bad news for Francisco Ayala and Larry Moran. Ayala needs to come here to TSZ so I can set him straight. From a paper in 2017, 7 years after Ayala criticized Meyer with Alus:
http://www.cell.com/trends/cell-biology/fulltext/S0962-8924(17)30002-8
And this forgotten study in 2009:
https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-10-563
I contributed my Alu research to various creationists organization and it is now showing up in some creationist publications. The most recent is by Chris Rupe and John Sanford!
For decades Darwinists have said repeating DNA in the human genome is obviously junk. That’s as silly as saying the identical copies of hundreds of computers in a server farm are junk merely because of repetition.
The issue is that Darwinists have said DNA that repeats must be junk since this DNA repeats itself as copies and they were so sure they figured out how biology actually works. The truth is they used evolutionary theory to argue something was non-functional, when in fact they actually didn’t do lab experiments to confirm their speculations. Now that lab experiments are being done, they are showing themselves to be wrong (yet again). This is especially bad for anti-ID evolutionary biologists like Ayala and Avise who made their case against ID because they said, “a Intelligent Designer would make DNA repeat itself so many times.” Ha!
So here is the article at Creation/Evolution Headlines. It also highlights a new book by Chris Rupe and John Sanford!
PS For the aficionados, the DNA discussed are transposon/SINE elements, but don’t get hung up on the technical jargon, “a rose is a rose by any other name.”
NOTE: the DNA RAM acts on two levels, one on the DNA genome in the form of Chromatin modifiable positions, and the other on the RNA transcriptome in the form of RNA editable sites
No, they haven’t. What they’ve said is that there is evidence that many different kinds of repetitive DNA is junk. Nobody has said that repetitive DNA must be junk merely because it is repetitive.
Please quote these people making these assertions.
Where did this take place? How sure is “so sure”, and what aspects of biology were they “so sure” they knew how actually works?
They used genetic load calculations to show that percentages of the genome was junk. These calculations in and of themselves do not say what parts of the genome specifically might be junk, other than it being most likely that it is non-coding regions.
Everything you write is superficial and vague bullshit. Curiously no quotes or references are given to people making the specific claims you ascribe to “Darwinists”.
Let me help you with that.
Palazzo, A. F., & Gregory, T. R. (2014). The Case for Junk DNA. PLoS Genetics, 10(5), e1004351. http://doi.org/10.1371/journal.pgen.1004351
Doolittle, W. F., & Brunet, Tyler D. P. (2017) On causal roles and selected effects: our genome is mostly junk BMC Biology 201715:116
https://doi.org/10.1186/s12915-017-0460-9
For anyone interested, the above articles give an actual case for junk-DNA. You will not find the superficial statements that Sal dishonestly tries to hinge on “Darwinists” in either of them.
Rumraket:
https://link.springer.com/content/pdf/10.1007%2Fs12052-010-0287-0.pdf
I also quoted Ayala. You didn’t like my characterization of Ayala’s folly? 🙂
Where is the bad news?
They’re transcribed by RNA polymerases. So what?
Nowhere does anyone say “it’s repetitive so it must be all junk”. Nor does some piece of DNA(repetitive or not) being transcribed by RNA polymerases constitute a demonstration that it functional.
You’ve failed to support your case. Game over, thanks for playing.
You seem to only be able to play these little rhetorical tricks and hope your audience doesn’t notice the sleight of hand taking place.
Sal, being able to find examples of ways in which an ALU CAN be functional does not demonstrate that all ALU’s ARE functional.
You understand this elementary concept right?
From one of the reviews (2017) I cited:
Evolutionary biologists are now in the unenviable position of arguing against experimental evidence.
There is evidence that excess DNA might serve some structural role in the chromosomes, but not informational. And that much of this excess bulk DNA had its origins in parasitic DNA (including Alus and Sines) serving as exaptation for later functionality.
For example, the non-random orientation of the X chromosome where the folding of Chromatin and exposure of different active regions to the “periphery” is dependent on the differentiation status of the cell type which fascinates me. That means, some of the intervening chromatin must be serving some nondescript “function” as bits and pieces are alternatively exposed or sequestered.
I still remember speculation in the good old days – when such speculation was referred to as facultative heterochromatin.
Ford Doolittle (in personal communication) did in fact suggest something along these lines was happening and also was subject to selection:
In general, exaptation of junk DNA happens all the time. The question remains whether the vast majority of junk DNA remains junk? … and what does “junk” really mean if it is playing the role of “clean fill” as Doolittle so succinctly suggested. At this point we are playing semantics.
I like the idea that somehow, all that intervening non-informational DNA is alternately and differentially exposing/sequestering crucial bits of expressed/nonexpressed DNA according to the developmental/differential/environmental response status of the cell.
In other words, this spacer DNA has to be reduntantly functional in some sense of the word, but not as first envisaged by ENCODE… and I believe I am understanding all this according to the Ford Doolittle quotes I cite?
Of course, there are two ways to look at the observation that rearranging junk DNA changes the expression of certain genes. First: The “junk” DNA has a regulatory effect on gene expression. Second: The darn junk DNA interferes with the regulation of gene expression unless it’s correctly folded out of the way.
Remarkable Karyotpe similarities of the Great Apes to my jaundiced eye indicate conservation and conservation would seem to imply function. Maybe I am being overly naïve.
https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-7-133
From a 2006 paper:
So why are the Alus over represented in this location in the genome?
Tom,
The Alus are information processing, but modifiable information, not just Read-Only-Memory. That’s what A-to-I editing is about. We shut that off, the creature dies.
I quoted a section that was favorable to Alus in a recent biochem textbook. That textbook wasn’t by Larry Moran, it was from a better regarded textbook by Neslon and Cox. 🙂
Sal,
Up to your old tricks, I see. You quote a claim, sometimes even with evidence, that some Alus (or whatever feature) are functional, and try to turn it into a fact that all Alus (or whatever feature) are functional. It doesn’t actually work that way.
Who says that Neslon & Cox’s text (by which you mean Nelson & Cox, by which you mean Lehninger) is better regarded than Moran’s?
Because they are more frequently exposed to insertion, due to frequent transcription?
Irony of irony. Evolutionary biologist hypothesis things on the sketchiest of evidence, and then when confronted with highly credible experimental evidence, they then start becoming skeptics and naysayers.
Oh well, so far it’s not looking good for Ayala and Avise.
Money talks, it’s #1 in Amazon in biochemistry.
https://www.amazon.com/gp/bestsellers/books/689711011/ref=pd_zg_hrsr_books_1_6_last
And this has got to hurt: Darwin’s Black Box ranks higher in biochemistry than Larry Moran’s textbook.
Such is life. The real question is how many Universities teach from DBB.
How will they find this out?
No, they aren’t. You’re still confused about the some/all dichotomy.
You mean some of the strongest evidence in all of science: comparative genetics.
What we are skeptical about are your grandiose extrapolations from isolated observations.
Again: some =/= all.
No amount of you claiming there is a discrepancy between theory and observation is going to make there be such a discrepancy.
It is looking entirely as solid as ever. Nothing has changed. At no point has anyone declared that there will never be found any functional repetitive, or non-coding, or SINE-derived, DNA.
NONE of the references you give come even close to establishing the conclusion you seek. They give isolated examples of where various forms of non-coding DNA have functional roles, and then they suggest how other such pieces of non-coding DNA could also be function. That’s it.
No, I mean evolutionary biology as in: