Dr. Stephen Meyer and Dr. Douglas Axe were recently interviewed by author and radio host Frank Turek on the significance of November’s Royal Society Meeting on evolution, in London. The two Intelligent Design advocates discussed what they see as the top five problems for evolutionary theory:
(i) gaps in the fossil record (in particular, the Cambrian explosion);
(ii) the lack of a naturalistic explanation for the origin of biological information;
(iii) the necessity of early mutations during embryonic development (which are invariably either defective or lethal) in order to generate new animal body types;
(iv) the existence of non-DNA epigenetic information controlling development (which means that you can’t evolve new animal body plans simply by mutating DNA); and
(v) the universal design intuition that we all share: functional coherence makes accidental invention fantastically improbable and hence physically impossible.
In today’s post, I’d like to focus on the third argument, which I consider to be the best of the bunch. The others are far less compelling.
Over at the Sandwalk blog, Professor Larry Moran and his readers have done a pretty good job of rebutting most of these arguments, in their comments on Professor Moran’s recent post, The dynamic duo tell us about five problems with evolution (January 14, 2017). Larry Moran’s earlier 2015 post, Molecular evidence supports the evolution of the major animal phyla cites a paper by Mario dos Reis et al. in Current Biology (Volume 25, Issue 22, p2939–2950, 16 November 2015) titled, “Uncertainty in the Timing of Origin of Animals and the Limits of Precision in Molecular Timescales,” which convincingly rebuts Meyer and Axe’s first argument, by showing that animals probably originated in the Cryogenian period (720 to 635 million years ago) and diversified into various phyla during the Ediacaran period (635 to 542 million years ago), before the Cambrian. I might add that we now have strong evidence that anatomical and genetic evolution occurred five times faster during the early Cambrian, at least for arthropods – although as Intelligent Design advocates have pointed out, that still leaves unanswered the question of how animal body plans arose in the first place.
Meyer and Axe’s second argument asserts that natural processes are incapable (as far as we can tell) of creating significant quantities of biological information – and especially, new functions or new anatomical features. Much of the argument rests on the alleged rarity of functional proteins in amino acid sequence space – a claim that was crushingly refuted in Rumraket’s recent post on The Skeptical Zone titled, Axe, EN&W and protein sequence space (again, again, again) (October 12, 2016). As for the claim that natural processes can’t create new functions, it’s simply bogus. The following three papers should be sufficient to demonstrate its empirical falsity: Five classic examples of gene evolution by Michael Page (New Scientist Daily News, March 24, 2009), Evolution of colour vision in vertebrates by James K. Bowmaker (Eye (1998) 12, 541-547), and Adaptive evolution of complex innovations through stepwise metabolic niche expansion by Balazs Szappanos et al (Nature Communications 7, article number 11607 (2016), doi:10.1038/ncomms11607).
I’m not really qualified to discuss Meyer and Axe’s fourth argument, but it seems to me that Professor Larry Moran has addressed it more than adequately in his recent post, What the Heck is Epigenetics? (Sandwalk, January 7, 2017). The last four paragraphs are worth quoting (emphases mine):
The Dean and Maggert definition [of epigenetics] focuses attention on modification of DNA (e.g. methylation) and modification of histones (chromatin) that are passed from one cell to two daughter cells. That’s where the action is in terms of the debate over the importance of epigenetics.
Methylation is trivial. Following semi-conservative DNA replication the new DNA strand will be hemi-methylated because the old strand will still have a methyl group but the newly synthesized strand will not. Hemi-methylated sites are the substrates for methylases so the site will be rapidly converted to a fully methylated site. This phenomenon was fully characterized almost 40 years ago [Restriction, Modification, and Epigenetics]. There’s no mystery about the inheritance of DNA modifications and no threat to evolutionary theory.
Histone modifications are never inherited through sperm because the chromatin is restructured during spermatogenesis. Modifications that are present in the oocyte can be passed down to the egg cell because some of the histones remain bound to DNA and pass from cell to cell during mitosis/meiosis. The only difference between this and inheritance of lac repressors is that the histones remain bound to the DNA at specific sites while the repressor molecules are released during DNA replication and re-bind to the lac operator in the daughter cells [Repression of the lac Operon].
Some people think this overthrows modern evolutionary theory.
So much for epigenetics, then.
The fifth and final argument discussed by Drs. Meyer and Axe relates to the universal design intuition. I’ve already amply covered both the merits and the mathematical and scientific flaws in Dr. Axe’s book, Undeniable, in my comprehensive review, so I won’t repeat myself here.
The “early embryo” argument, helpfully summarized by Dr. Paul Nelson
That leaves us with the third argument. Looking through the comments on Professor Moran’s latest post, it seems that very few readers bothered to address this argument. The only notable exception was lutesuite, who pointed out that examples of non-lethal mutation in regulatory DNA sequences are discussed in a paper titled, Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change by M.Z. Ludwig et al. (Development 1998 125: 949-958). The paper looks interesting, but it’s clearly written for a specialist audience, and I don’t feel qualified to comment on it.
As it turns out, I wrote about the “early embryo” argument in a 2012 post, when it was being put forward by Dr. Paul Nelson. Nelson handily summarized the argument in a comment he made over at Professor Jerry Coyne’s Website, Why Evolution Is True:
Mutations that disrupt body plan formation are inevitably deleterious. (There’s only one class of exceptions; see below.) This is the main signal emerging from over 100 years of mutagenesis in Drosophila.
Text from one of my Saddleback slides:
1. Animal body plans are built in each generation by a stepwise process, from the fertilized egg to the many cells of the adult. The earliest stages in this process determine what follows.
2. Thus, to change — that is, to evolve — any body plan, mutations expressed early in development must occur, be viable, and be stably transmitted to offspring.
3. But such early-acting mutations of global effect are those least likely to be tolerated by the embryo.
Losses of structures are the only exception to this otherwise universal generalization about animal development and evolution. Many species will tolerate phenotypic losses if their local (environmental) circumstances are favorable. Hence island or cave fauna often lose (for instance) wings or eyes.
Obviously, loss of function is incapable of explaining the origin of new, viable body plans for animals.
A hole in the argument?
On the face of it, Nelson’s three-step argument certainly looks like a knock-down argument, assuming that the premises are factually true. But are they? A commenter named Born Right made the following response to Dr. Nelson over at Jerry Coyne’s Website (emphases mine):
Paul Nelson,
Lethal mutations will kill the embryo. But what you’re totally failing to understand is that not all mutations are lethal. Many are tolerated. I heard you cite the example of HOX gene mutations in flies and how altering them kills the embryos. You didn’t mention the entire story there. Do you know that there are wild populations of flies having HOX gene mutations? Even in the lab, you can create viable HOX-mutant flies that have, for example, two sets of wings. In fact, simple non-lethal mutations in HOX genes can profoundly alter the morphology. It is these non-lethal mutations that natural selection “cherry picks”, provided they confer a survival advantage on the organism.
Many mutations actually arise as recessive mutations, not as dominant ones. They spread through the population remaining dormant or having a mild effect, until there is a sufficient number of heterozygotes. Then, interbreeding between heterozygotes will cause homozygous mutations to arise suddenly throughout the population. If the new feature improves survival & reproductive success, it gets rapidly selected…
Macroevolution is a gradual response to climate change and other environmental pressures. Organisms accumulate non-lethal mutations that changes their body plan bit by bit until they are well adapted to their changing habitat.
However, a 2010 Evolution News and Views post co-authored by Dr. Paul Nelson, Dr. Stephen Meyer, Dr. Rick Sternberg and Dr. Jonathan Wells, contests the claim that Hox gene mutations are non-lethal. The authors assert that such mutations are, at the very least, defective:
Mutations to “genetic switches” involved in body plan formation … disrupt the normal development of animals. With the possible exception of the loss of structures (not a promising avenue for novelty-building evolution, in any case), these mutations either destroy the embryo in which they occur or render it gravely unfit as an adult. What the mutations do not provide are “many different variations in body plans.”…
… [T]here are solid empirical grounds for arguing that changes in DNA alone cannot produce new organs or body plans. A technique called “saturation mutagenesis”1,2 has been used to produce every possible developmental mutation in fruit flies (Drosophila melanogaster),3,4,5 roundworms (Caenorhabditis elegans),6,7 and zebrafish (Danio rerio),8,9,10 and the same technique is now being applied to mice (Mus musculus).11,12
None of the evidence from these and numerous other studies of developmental mutations supports the neo-Darwinian dogma that DNA mutations can lead to new organs or body plans–because none of the observed developmental mutations benefit the organism.
Indeed, the evidence justifies only one conclusion, which Wells summarized in his last slide at SMU:
“We can modify the DNA of a fruit fly embryo in any way we want, and there are only three possible outcomes:
A normal fruit fly;
A defective fruit fly; or
A dead fruit fly.”
The Wikipedia article on Drosophila embryogenesis may interest some readers.
What I would like to know is: are the Hox mutations in fruitflies mentioned by Born Right in his comment above neutral or deleterious – and if the latter, are they only slightly deleterious or highly deleterious?
A follow-up comment by Born Right
In a subsequent comment over at Why Evolution Is True, Born Right cited two scientific references in support of his claims:
Paul Nelson,
Fantastic new research shows how fish developed limbs and moved onto land. Boosting the expression of Hoxd13a gene in zebrafish transforms their fins into limb-like structures that develop more cartilage tissue and less fin tissue!
http://www.sciencedaily.com/releases/2012/12/121210124521.htm
http://www.sciencedirect.com/science/article/pii/S1534580712004789
Importantly, the overexpression of Hoxd13a in zebrafish was driven by a mouse-specific enhancer. This shows that the regulatory elements acting on the enhancer are present in both fishes and distantly-related mammals!
The first paper, titled, From fish to human: Research reveals how fins became legs (Science Daily, December 10, 2012) is written in a style that laypeople can readily understand. I’ll quote a brief excerpt (emphases mine):
In order to understand how fins may have evolved into limbs, researchers led by Dr. Gómez-Skarmeta and his colleague Dr. Fernando Casares at the same institute introduced extra Hoxd13, a gene known to play a role in distinguishing body parts, at the tip of a zebrafish embryo’s fin. Surprisingly, this led to the generation of new cartilage tissue and the reduction of fin tissue — changes that strikingly recapitulate key aspects of land-animal limb development. The researchers wondered whether novel Hoxd13 control elements may have increased Hoxd13 gene expression in the past to cause similar effects during limb evolution. They turned to a DNA control element that is known to regulate the activation of Hoxd13 in mouse embryonic limbs and that is absent in fish.
“We found that in the zebrafish, the mouse Hoxd13 control element was capable of driving gene expression in the distal fin rudiment. This result indicates that molecular machinery capable of activating this control element was also present in the last common ancestor of finned and legged animals and is proven by its remnants in zebrafish,” says Dr. Casares.
This sounds fascinating, and to me it constitutes powerful evidence for common ancestry, but the real question we need to address is; exactly how early in the course of the zebrafish’s embryonic development did these mutations take effect?
The second paper cited by Born Right (“Hoxd13 Contribution to the Evolution of Vertebrate Appendages” by Renata Freitas et al. in Developmental Cell, Volume 23, Issue 6, pp. 1219–1229, 11 December 2012) is much meatier, because it’s the original papaer on which the Science Daily report was based. The authors contend that “modulation of 5′ Hoxd transcription, through the addition of novel enhancer elements to its regulatory machinery, was a key evolutionary mechanism for the distal elaboration of vertebrate appendages,” and they conclude:
Within the developmental constraints imposed by a highly derived teleost fin, our results suggest that modulation of Hoxd13 results in downstream developmental changes expected to have happened during fin evolution. This, together with the evidence we provide that the upstream regulators of CsC were also present prior to tetrapod radiation, makes us favor an evolutionary scenario in which gain of extra 5′ Hoxd enhancers might have allowed the developmental changes necessary for the elaboration of distal bones in fishes that evolved, ultimately, into the tetrapod hand.
This sounds a lot more promising, but after having a look at it, I’m still rather unclear about exactly how early these hypothesized mutations would have had to have occurred, in the course of vertebrate embryonic development. Perhaps some reader can enlighten me.
Well, that’s about as far as my digging and delving has taken me. I’d like to throw the discussion open at this point. Are there any known examples of early embryonic mutations which are not deleterious, and do they shed any light on how new animal body plans might have evolved? Over to you.
(Note: the image at the top [courtesy of Wikipedia] shows the ventral view of repeating denticle bands on the cuticle of a 22-hour-old Drosophila embryo. The head is on the left.)
Except you don’t have any idea what you say is true. You have no way to test that claim.
Tell you what, Larry, when you can design a human being using your choice of 10% of the current genome, people will believe you. Until then, seeing that you really don’t know what is actually going on inside of a cell, you shouldn’t talk as if what you say is a fact.
To get a taste of the cutting edge of lncRNA research, consider the latest work coming out of John Rinn’s lab at Harvard (Rinn was the discoverer of HOTAIR).
lncRNA can be used as scaffolds or anchor points in a coordinated way to get the chromosomes and chromatin to orient themselves in a way that affects gene regulation.
The caption for the picture below:
Sorry, here is the picture:
An interesting turnaround, considering you had been calling Larry an idiot before he showed up here.
That sudden turn in behavior is honestly quite pathetic. Omg Larry you’ve taught me so much and I’m so grateful. But … you know nothing, you’re an idiot and by extension anyone of those “faith heads” who listen to you. And oh btw you’re trying to destroy science with your evolutionism. What was it, Larry “82.5 Megabytes” Moran? (btw Sal I misread you earlier, you wrote ‘bytes’ and I read it as ‘bases’).
Earlier in the thread you seemed to be working hard to portray people like Larry Moran and Dan Graur as idiots who are somehow in conflict with all those “lab researchers actually doing the experiments” with their many million dollar NIH grants, or someting to that effect. In contrast to these “old” theoreticians who’ve never set foot in a lab.
Of course, this is that well-known trope about those out-of-touch lofty academics, sitting in their university offices and ivory towers, while the good ole hard-working manual laborers are the ones who really knows how the world works.
This is particularly ironic coming from Salvador “Baghdad Bob” Cordova. Hey Sal, how much time have you spent in a lab these last 3 years? Did you get a greenscreen photo taken?
Btw:
Yes, they can be. That would be how those of them which are functional, would be functional. It doesn’t follow they all are. Just because you can point to a reference that details how a lncRNA might function doesn’t in any fucking way serve as substantiation of your desperately sought conclusion that all lncRNAs are function.
It’s almost as funny as when Sal found out one of the people he was talking to at ATBC was a professor of physics at his university.
That wasn’t my point. My point is that it’s hard and complex to discover function, and Cat’s cradle is one example of how difficult it is to actually put together models of how lncRNAs can function. Rinn has had a track record of success, and given his success with discovering the function of the FIRRE lncRNA, he has good reason to advance the Cat’s cradle hypothesis.
I didn’t say cat’s cradle would demonstrate that all lncRNAs functional, or that all lncRNAs are functional. I’m just saying it’s premature to be so dismissive that they are mostly junk, and it’s unhelpful, probably damaging to scientific progress to have the attitude it junk till proven otherwise just to maintain the 82.5 Megabyte hypothesis of human complexity (an absurdly low number just on the face of it).
The cat’s cradle hypothesis, if true, would make a lot lncRNAs functional, and I’ve said many times here at TSZ, physical scaffolding as opposed to some sort of chemical activity is how DNA can be used, and it turns out also this is how RNA can be used (as evidenced by Rinn’s discovery of FIRRE).
I highlighted the cat’s cradle hypothesis to show that discovering function for ncRNAs is non-trivial and follows along lines that are usually not expected. Who would have thought the linc/lnc RNA HOTAIR would work the way it did? It was shocking when it was discovered. The journal reporting it said Rinn’s discovery was the best ever reported by their journal. After HOTAIR, Rinn discovered FIRRE with great effort.
The lab at Harvard and partnerships lead to discover the function of the FIRRE lncRNA involved this many authors:
And that’s what it took to discover function for just 1 lncRNA!
Larry then starts mocking the slow progress. Given the evident difficulty of the task to find function in just one lncRNA, one would think Larry would show a little more patience for the discovery of function for other lncRNAs given the fact there is well established correlation (and hence at least the possibility of causation) of lncRNA mis-regulation and disease. Instead he just gives more dismissals.
The reason the medical community strongly suspects lncRNAs and other ncRNAs are functional is because of GWAS (genome wide association studies) of sick people contrasted with healthy people. Diseases are often correlated with these regions Larry calls junk, and it seems to me irresponsible not to at least look to see if there is correlation because there is causation, or at the very least correlation that will serve as a good medical diagnostic marker.
As can be seen here:
https://www.encodeproject.org/search/?type=Experiment&lab.title=John+Rinn%2C+Broad
Rinn was part of the ENCODE project, whom Larry’s associate Dan Graur referred to as “ignoramuses, crooks generating piles of excrement”.
Rinn’s discovery of FIRRE combined with the 3C, ….Hi-C series of experiments contribute to the Cat’s cradle model.
But look at the FIRRE interaction. It sits on the X chromosome, then simultaneously attaches to Chromosome 2 and Chromsome 17 to affect regulation through chromatin conformation changes. And that’s just the action of one measly lncRNA. And you could see the HOTAIR lncRNA did its regulation through a totally different mechanism. So there is no one-size-fits-all mechanism of function for lncRNAs. Figuring this stuff out ain’t trivial. But all this nay-saying by Graur against ENCODE researchers like Rinn isn’t very helpful is it, nor is it helpful for Larry to write off large numbers of lncRNAs merely because he wants to reduce the complexity of humans to 82.5 Megabytes.
Graur and Larry advocated defunding various experiments. Well what class of experiments do they recommend defunding from the ENCODE follow on (RoadmapEpigenomics) and other labs around the world? RNA-seq experiments, Chip-Seq, Bilsufide experimetns, 3C….HI-C experiments. What about those experiments qualifies them as generating “excrement” (to use Gruar’s own words)?
Depicted below a diagram from RInn’s paper on is the FIRRE lncRNA affecting chromatin confirmation by linking the X, 2, 17 chromosomes through the hnRNPU factor.
I would love there to be more functional RNAs. I’m no protein chauvinist. RNA lies at the heart of it all, don’t you know … ‘messenger’ my eye!
But let’s get the data first, eh?
“Wild Speculation”? Was Larry possibly referring to John Rinn’s Cat’s cradle hypothesis published, not on a blog, but in a peer-reviewed article June 2, 2016?
Rinn said in that paper:
Bwahaha!
Rinn references the following paper which suggests to me the Intelligent Designer has a sense of humor.
A lncRNA gene (called lockd DNA) is indicated to regulate another gene (in this case the Cdkn1b gene), but its lncRNA transcript (lockd RNA) doesn’t actually regulate the Cdkn1b gene! Too funny. Rinn then points out, the act of transcribing the lncRNA however changes chromatin conformation.
Wildly speculative? Well, if it has experimental evidence backing it up, it’s not that speculative, and on much better ground than missing transitionals. And who should we bet on, Dan Gruar or John Rinn (who actually researches lncRNAs and discovered function for them)?
This is not surprising given the behavior machines attaching to the Vitamin D receptor binding sites (I shared this with colewd last year through videos of Wesley Pike’s ENCODE 2015 presentation) which would suggest this sort of Rube Goldberg behavior for lncRNAs is the way things are done in the nucleus. It now adds an insane level of complexity to the protein interactome. This is the most incredible Rube Goldberg machine in the universe. Praise the Lord!
The graph that follows your post is quite possibly one of the most meaningless graphs I have ever seen. They list “eukaryota” as if it was a separate thing, yet pretty much everything else in their list are eukaryotes. And these organisms did not originate from each other, they share common ancestors. And since orphan genes mostly evolve from non-coding areas by chance accumulation of mutations resulting in areas that look like transcription factor binding sites (and since it takes relatively few mutations to significantly impact the binding strength and activity of said transcription factors), and since these areas are already thought to undergo highly stochastic change, why the hell would they not show variation in the number of detected orphan genes?
Unless you actually bother to look at the DNA sequences of these so-called orphan genes (they’re homologous, so no.. this DNA doesn’t just pop up out of “poof”)*, rather than try to speciously just list “how many there are” from some handpicked and rather meaningless taxonomic groups.
Serously. “Poof”? You believe in the “poof”-mechanism? A grown fucking man who believes that things just …poof into existence? How’s that for an “explanation”. Oh gee, I can’t make intuitive sense of this pattern. Well, maybe it just POOFED into existence as-is. There you go guys. “Explained”.
Said the angry boy, as he cries about everyone being so angry.
I am sure the mods will never see this as attacking the poster. So go on then with your little cry fit.
Rumraket,
More rules breaking that the mods won’t care about. Only Frankie breaks the rules.
I’m looking now. If you’re unhappy with some aspect of the comment, report it in the moderation issues thread or PM me
Alan Fox,
The comments are staring you right in the face Alan. But you only see what you want to see, so its not going to be useful.
Your idea of when a comment is addressing the post or the person posting is very flexible, depending on who is doing the posting.
Getting back to you on this, it just occurred to me it may have relevance to Larry’s LOLAT Lambast of lncRNAs. Larry said many lncRNAs have too low a level of expression to be functional. He called these lncRNAs “LOLATs”, and went on to lambast those who would dare to call such LOLAT lncRNAs functional.
But, the pioneer and ENCODE-funded scientist at the Harvard Broad Institute by the name of John Rinn argues these LOLATs are critical to creating chromatin conformations. Rinn published a publicly accessible essay through the NIH that explain the importance of chromatin conformation, and guess what the chromatin conformation system is called. It is called (TADA):
“The Origami Code”.
I mentioned in passing experiments known as the “C” experiments. They are 1C,2C,3C,4C,5C,6C and High-C experiments that unravel the Origami Code. The ENCODE project did a lot of 5C experiments, but the High-C experiments are the top of the line of C experiments.
The video is of the Origami Code of the DNA. It shows how the chromatin reconforms itself to do gene regulation for different cell types. This is relevant to chromatin extrusion loops which are defined by the Alu elments (mentioned earlier). It is relevant to the LOLATs which Rinn is showing likely enable the implementation of the Origami Code. So Larry is almost definitely wrong about the Alus (important for CTFC chromatin loops and A-to-I editing of dsRNA loops), and now we see reason as to why Larry’s LOLAT lambast may also be wrong as well.
Watch the video below to see the experimental insights of the Origami Code. Those chromatin extrusion loops defined by the Alus pop up in the vidieo, and Rinn lncRNA FIRRE discovery and his cat’s cradle hypothesis relate to all this. Now we’re talking real science. Bwahaha!
http://news.rice.edu/2014/12/11/3-d-maps-reveal-the-genomes-origami-code/
To understand the DNA Origami code see this video:
Rinn explains the role of lncRNAs (which would include Larry’s LOLATs) in implementing the Origami Code in his NIH publication here:
http://authors.library.caltech.edu/49845/13/nihms631739.pdf
Praise you Jesus, the Intelligent Designer of the Rube Goldberg Machines of life! Halelujah! Glory to God, Amen!
PS
Just for your entertainment, just to show the powerful ability of DNA to be folded like into Origami art (necessary for higher gene regulation) here is an Origami Bunny formed from DNA.
http://www.zmescience.com/science/biology/folding-tiny-dna-automated-printing-0423534/
@Sal Cordova,
I coined the term LOLAT to help distinguish between putative functional RNAs and lncRNAs with a known function. The question before us if how many of the thousands of transcripts are actually functional. Calling them lncRNAs when you don’t know whether they are functional introduces a bias in the discussion.
You demonstrate the problem when you refer to Rinn’s papers. His group has provided evidence that some of these RNAs have a function. He refers to those functional RNAs as lncRNAs but he doesn’t distinguish between the small fraction with proven functions and the much larger fraction that may be junk. They are all lncRNAs in his mind.
You fell into the trap. You automatically assumed that because a few of them have a function then all of them have a function.
And the Gish Gallop continues. Based on the diagram, this folded DNA is nothing at all like the folding you describe in the actual nucleus. It’s all a single molecule with the “stems” formed by base-pairing of single strand sections in different spots. Can’t tell how many actual strands there are. Maybe just one? So entirely irrelevant to your latest sally, which has itself wandered so far from the thread topic that you can’t see it from there.
The Bunny shows the importance of sequence specificity in creating 3D DNA conformations as well as the delicate conditions needed to achieve a particular conformation.
That means a lot of the DNA/RNA complexes (as seen in diagram of the FIRRE lncRNA joining the X, 2, and 17 chromosomes) to function properly must have pretty good sequence constraint both in the DNA and the RNA and a host of highly special conditions.
The man-made DNA Origami bunny is nothing compared to the complexity of real-life chromatin that is also organized with nucleosome/histones and works within RNA scaffolding and has protein molecular machines attaching sections. How hard it was for man to even imperfectly mimic a small fraction of what God has done in the cell?
I sense almost revulsion at the possibility that life is full of staggering complex function as demonstrated by DNA Origami Codes that may well be implemented with lncRNA scaffolds like FIRRE, NEAT1, and XIST and have epigenetic regulation through histones to boot with lncRNA transcripts like HOTAIR. Additionally, I pointed out above, the gene locus of the lncRNA may serve one function whereas the RNA transcript of the lncRNA may serve another! But rather than amazement at seeing this incredibly complex design, I see revulsion, nay-saying.
For years the net has been debating the function of “junkDNA”, and now that I start to enumerate it, all you do is label it as a Gish Gallop. I’d think people interested in science should sooner say, “Wow! That’s amazing how biology works. Thanks, Sal for sharing about the Origami Code and Alu roles in chromatin looping, and A-to-I editing, and LINE-1’s role in self-modifying the DNA in somatic cells, and the importance of tandem repetitive DNA in providing a location for Epigenetic RAM.” Instead, you complain that I’m just galloping.
No, I’m defending my point that lots of DNA claimed by your side to be junk isn’t. What? You don’t like the way I’m driving home the point by actually citing and relating cutting edge research at the NIH and places like the Broad Institute of Harvard or Cold Spring Harbor Laboratories? What have you provided in response to these experimental findings? Just complaints about me, not really talking about the scientific discoveries and how they support or refute the claims of DNA/RNA functionality.
That’s just ridiculous.
It’s the kind of complexity that no real (observable, etc.) designer could handle, but only evolutionary processes could process and coordinate into a coherent whole.
We know that. You gape with “amazement” and incomprehension. That’s what ignoring what the evidence shows gives a person, amazement and lack of understanding.
Glen Davidson
stcordova,
Hi Sal
Very interesting posts. Thanks. Do you have an opinion of how many regulatory RNA’s are dedicated to embryo development. I could imagine low levels of expression in adults because the ncRNA’s were dedicated to building the animal.
No it doesn’t. It’s made by an entirely different means than anything in the nucleus. These are stretches of single-stranded DNA that find their complements to produce short stretches of double-stranded DNA. Absolutely no relevance to what DNA does in organisms. But it’s a fine example of how you can trot out stuff you don’t understand in the belief that it supports your preconceived opinion, while ignoring everything that doesn’t.
Hi Cole, thanks for reading. I hope you noticed I mentioned Wesley Pike’s work on the vitamin D receptor. 🙂
I don’t have any answer to your question since I don’t know.
It might be better to ask how many RNA bases are involved. In principle there could be more RNA bases than actual DNA bases because of alternative splicing and A-to-I editing.
Not only that, RNAs may be inherited between cell cycles. That is to say, many RNAs currently used by a cell may have originated several cell cycles previously. We know that embryos likely leverage mRNAs that were front loaded into the embryo and not necessarily transcribed solely by the embryo. This was confirmed by experiments on enucleated cells developing to the blastula stage.
As you can see from the Origami Code, the traditional meaning of regulatory RNA could be blurred. The FIRRE diagram illustrates new concepts in DNA regulation via RNAs forcing chromatin conformation changes.
So I don’t have any idea, but a rough guess is maybe on the order of the size of the genome, but that is pure speculation, and not anything I would really attempt to defend as hard and fast.
Further, the RNA genes are dual purpose. They make RNA transcripts involved in various functions, but the DNA genes themselves serve as scaffolding points for molecular machines. We saw this with the Vitamin D receptor, so it’s not just the RNAs regulating, but the DNA/Chromatin/histone complexes from where these RNAs emerge.
I’m sorry I have no hard and fast numbers for you. We may not have a handle on it even after several decades of research. Living things are immensely more complex than has been suggested even in textbooks.
And as I’ve argued, I really don’t think the majority of heritable information is in the DNA anyway, it’s outside the DNA, but just not in a form that is as mutatable like the single-point-of-failure DNA. Thus the heritable information outside DNA was not blatantly obvious and missed by most researchers because it wasn’t single-point-of-failure mutatable, but had redundancies on the order of 100 layers (the mitochondria being an example).
I should add, this non-DNA inheritance does not at all conflict with even a strict view of the Central Dogma since the Central Dogma (outside of protein coding) has nothing to say of structural and developmental instructions.
lol
What the hell does this even mean? At this point you’re straight up blathering.
Well at least he’s not out abusing children! Right Patrick?
stcordova,
What a great post and the defending of what you know is true!
The so called “experts” (Moran, Harshman, and other big names in Darwinian leaky bs hiding under rumrockets and so on) won’t like it no matter what proof you present because it takes away the big chunk of their faith they based their egos on…You are chipping it away…bit by bit…
Congrats stcordova! You’ve won me over!
stcordova,
Your claim here is supported as part of drosophila development as part of how the protein bicoid is produced in the fly embryo. Bicoid reminds me of the animal protein beta catenin that is regulated by vitamin d. Beta catenin is very active in embryo development but is down regulated by vitamin d when the cell is in normal operation. Bicoid is precisely regulated in drosophila embryo development. I do not agree with Larry that low levels of gene expression indicate that the gene is non functional. It may simply be the condition of the cell at the time of measurement.
There are two additional lectures that will pop up when you go to the link below.
I think he means if stuff was different stuff would be different so stuff is special because if it was different then, er, multiverse?
Praise Odin! Also, man can’t create, or even lift a mountain, yet entire solar systems have coalesced under the blind force of gravity. For literally millenia of human history, man dreamt of being able to fly. For all that time it remained vain dream until finally, God made the first flying machine in 1908.
I have no doubt you sense lots of nonexistant things. That seems to be a diagnostic trait at this junction.
Maybe so, maybe some of the time. Maybe not in the vast majority of cases.
Revulsion at complexity? You see a lot of things that don’t exist.
Enumerate it? What the hell does that even mean?
If all you did was just to bring information for it’s own interesting and informative sake. But it isn’t, rather you’re you’re trying to deceptively mislead people with a lot of irrelevant blather that doesn’t get you to the conclusion you’re so desperate to reach.
What’s worse, you want to be thanked for this shit?
No, to defend that point you’d have to be actually bringing evidence that contradicts what we’re saying. We already know some lncRNAs, ALUs and so on, are functional. You don’t get to claim that merely quoting a reference that details how some of those few RNA transcritps which are functional, happen to work, constitutes evidence that they all are. Sorry, it simply doesn’t follow.
Nobody here is saying they’re all junk. So pointing to a few that are functional isn’t a refutation of the claim for junk, since the case for junk isn’t contingent on all of them being junk. You’re extrapolating from isolated cases to MILLIONS of transcripts.
You can’t get to there from here.
You don’t “drive home the point” by pathetically namedropping the NIH and Harvard, or by using the phrase “cutting edge research”.
Oh man, Harvard you say? HARVARD? And cutting edge? Well fuck me, I guess that means it’s all functional.
Do we really need to point out that it doesn’t fucking matter where the research was done? What matters are the numbers, not the names of famous or prestigous institutions. Or how many abbreviations you can type or how much technical jargon you’ve memorized. Or how many graphs and diagrams you can paste from papers you didn’t write about research you didn’t do, that still doesn’t get you to the conclusion you wishfully seek?
Highlights of your endless list of fallacious inferences? Calls for critical thinking about grandiose claims researchers feel the need to make to get their work published? Expositions of your desperate search for, and extrapolation towards a conclusion not borne out by the evidence? Your abuse of that classic trope about lofty, out-of-touch academics being contradicted by real, hard-working researchers?
Now you know why I find Salvador so endearingly lovable! Some people might call that “full of shit,” but not me!
So what’s it contingent on? Evolutionary theory? So how is it so many who accept evolutionary theory (like the guys in ENCODE) believe DNA is mostly functional?
Goes to show, as far as the question of functionality, evolutionary theory isn’t much of a theoretical guide is it? Did evolutionary theory solve the functionality of the FIRRE lncRNA? No. Why then do you expect it to solve the question of other lncRNAs functionality including the LOLATs. Why the rush to judgement?
Something makes the Origami Code conformations happen. You think that happens willy nilly? Guys who actually work with the C experiments that elucidated the Origami Code suspect lncRNAs are involved.
Misrepresentation. The references show they could be functional, not that they necessarily are. Whereas Larry’s 82.5 Megabyte hypothesis insists 90% of the genome is definitely, unquestionably junk. That’s not being very open minded is it?
You want to plug your ears to the scientific possibility that maybe a good part of the 90% that Larry is so eager to write off is functional, that’s up to you. I just find your rush to judgement comical and presumptuous.
Even after you see the Origami Code which must be operating differently in at least the 213 (actually maybe thousands if Tjian is right) of cell types, you’re sooooo sure something as complex as that can’t possibly leverage the 90% Larry is writing off. Nope not possible. Talk about faith in the total absence of direct observation and in the face of contrary evidence.
That’s all right, the matter isn’t settled. 20 years from now we may know more, and we may find function. But in contrast, you and Larry are staking your hopes on something that even if right (junkDNA), it has no payoff except to reassure yourselves that you’re 90% junk.
It’s hard not to see the comedy in this. You guys keep insisting, “we’re junk we’r junk, we’re purposeless junk.” And I say, “no you’re not, you are fearfully and wonderfully made. You just have lots of reminders (like death and sickness) that you aren’t God.” But you keep insisting, “we’re junk we’re junk, and we’ll keep fighting to prove the point we’re junk.”
You don’t see this dogged determination to prove to yourselves and the rest of the world that you are purposeless junk is a bit comical?
Whoa, what an embarrassing and self-revealing rant. This is the bit that impressed me the most:
You have more or less admitted that you choose your opinions based on what would make you feel good. And you have committed whatever fallacy it is (forget the official name) when you impute moral character to non-human objects. Having a genome that’s 90% junk doesn’t affect your worth as a human being one way or the other. As Donald Trump would say, “sad”.
Where did I represent that this DNA bunny was made by biological means when it was clearly man-made? I wasn’t trying to represent that this is exactly what happens in biology. I mean, you don’t expect DNA in the cell to make shapes of coke bottles and bunnies like the man-made DNA did, do you?
This man-made complementation process wasn’t what I was trying to convey, nor was I representing that this is how single strands of DNA become doubles strands.
Baloney, I’ve provided descriptions at TSZ regarding the process of DNA replication which involves the Polymerase III synthesizing the double strand at the single strands of the replication fork. You’re claim that I don’t understand this nor have ever talked about this is indefensible. For the readers’ benefit, a diagram similar to many that I have posted at TSZ many times is below. Yet you have the gall to accuse me of not understanding how double stranded DNAs are synthesized from single strands.
What I was trying to convey with the Bunny is the importance of sequence to the biophysical ability of DNA to make certain conformations either alone or with other chemicals. This is true for small stretches of DNA in the formation of nucleosomes and quadruplex DNA structures in telomeres, but when DNA is combined with RNAs and proteins or whatever, this leads to spontaneous self assembly of higher order chromatin structures.
The binding of RNAs and proteins to DNAs often involves DNA sequence specificity, or some sequence motif (like tandem repetition). The point of what I was saying is the DNA sequence is important for achieving self-organizing chromatin conformations, it is not as tolerant to change as many suppose.
An example of this is the multiple copies of specific heterochromatic DNA in Schizosaccharomyces pombe whose involvement in cohesion binding has been experimentally proven. See:
https://en.wikipedia.org/wiki/Cohesin
Oh, yeah, yet another evidence of the function of repetitive copies, which guys like Avise are so quick to dismiss.
For future reference, the importance of repetition in DNA:
and here is another paper that highlights the point I was trying to make. Since you’re making such an issue about the Bunny, I may as well give you a little more of an onslaught of what I was trying to say regarding the importance of DNA sequence in gene regulation so you have less room to complain. Sequence affects conformation because it affects native DNA curvature (the nucleosome code) and the binding affinities which affect what binds to it and hence its conformations and hence also its regulation.
http://www.sciencedirect.com/science/article/pii/S0378111909000328
WHOA! Thanks colewd. I have zero formal background in embryology and developmental biology. Studly find on your part. I’m indebted to you sir!
Biocoid is life critical and it’s an orphan gene! Yay!
Eric Wieschaus points out the spatial distribution and concentration of bicoid mRNA is quantitative information in and of itself.
And thanks for backing up my point on many mRNAs being front loaded rather than transcribed in embryos. I didn’t know this fact was that well-known (from the way the TSZ regulars seemed to react).
The mother’s DNA may code the bicoid mRNA, but DNAs don’t immediately determine the mRNAs assymetric spatial distribution (to mark out head and tail of the child). For that matter, I don’t know that anyone knows what actually drives the patterning of bicoid distribution in the first place. To the extent the bicoid mRNA and bicoid proteins are spatially distributed because of the cytoplasmic structure, then this also shows that DNA does not store the blueprint the biocoid aspects of embryonic development.
Thanks. You may enjoy my discussion of YEC stuff here:
It starts to get fun as the conversation in the comment section develops. 🙂
J-Mac,
Because up until this point, you were wholly in the other camp? Or even on the fence?
It’s not so much a gallop as a flurry. It’s snowing hard, and you have to try and catch all the snowflakes afore they hit the ground.
Really?
OMagain,
Indeed. My eyebrow went up a notch too. I give it an hour before expertise asserts itself.
stcordova,
Not that life critical, then.
So on the one hand we have bilaterian-wide homology in Hox genes. That’s Common Design, that is. We also have a TRG in fruit flies. That’s … Uncommon Design, that is. Whatever the pattern, it’s exactly what we’d expect from design. Or at least, definitely not what we’d expect from evolution. Because that would always be whatever-it-isn’t. Design being whatever-it-is.
J-Mac illustrates the issue here. An eagle’s eye view of these threads sees Cordova el Héroe batting these evolutionists with one hand tied behind his back. Long post from stc, complete with pretty picture. Refutations of specific points by knowledgeable people, occupying somewhat less space. More from stc, more pictures (you think I don’t understand polymerase? Here’s a cartoon that proves I do!).
Sal,
If you have such insight into biology and know the reality of how things actually are, will you be publishing a paper on your “insights” any time soon?
It would probably be shorter then the posts you’ve already made on this page. But then you’d have to actually support your claims, so no, I guess you won’t be doing that will you.
What I’d like to know is if those mutations were intelligent designed or not?
stcordova,
You don’t think anything rooted in DNA controls the distribution of proteins and RNAs? How is ‘cytoplasmic structure’ maintained, independently of anything in DNA, from egg to egg?
The cell, Allan- the cell did not grow from DNA alone. DNA cannot do anything without pre-existing proteins, ribosomes and more,
The designer can’t possibly design kinds one mutation at a time, so lots of them are needed!
Isn’t it funny? apparently a single mutation in HOX genes must be deleterious or lethal, therefore a bunch of them plus tons of other needed coordinated mutations in regulatory and protein coding genes must have happened all at once. This will surely produce descendants unable to interbreed with their own population, so LOTS of this must have happened to produce a large enough population of the new “kind”.
As petrushka likes to put it: Invent a problem, imagine the solution… and of course, ignore the conflicting evidence.
ID at it’s best
First round coming out soon. The publisher is finishing a few things. That publication isn’t my best stuff. My best stuff is being worked out with someone from a major newspaper.
Some other stuff already in private circulation in the ID community.
The TSZ comments were my editorial session with so many free-of-charge reviewers. Thank you very much!
That was my favorite typo of all time. Thank you so much.
You completely misunderstood what I was trying to criticize you for, twice. I don’t have the energy right now to go into it though.
Plenty in the DNA controls distribution of proteins, like Yamanaka factors. Where did I say otherwise?
I was pointing out lots of thing are not under direct DNA control, like the structure of glycans or various organelles.
stcordova,
My comment was in response to this:
You were specifically talking of these protein and RNA distributions. You were claiming that this was an example of exception to ‘DNA control’. I was wondering how it survived the passage from egg, via zygote and through the germline/soma bifurfaction (where it controls development in the latter, merely being extra-chromosomally preserved in the former), and on into the next egg (if the germline is female). If, that is, the control is not rooted in DNA, but is instead rather vaguely located ‘in cytoplasm’.