In fact, as I tried to explain to Paul Nelson back here:
Hey, you were also present in that thread and you appear to have learned nothing from it.
2 Likes
That’s a flat out lie.
What they are saying is that conservation over deep time gives a strong indication of function. They are not saying there can be no function in less conserved DNA. Nor are they saying mutations implicated in disease in GWAS should not be studied just because they might lie in genomic regions with poor conservation.
Can you take a break from your lies please? You tell so many egregious and misleading falsehoods it’s honestly rather disgusting to see you keep doing this. What kind of person are you, really?
3 Likes
Can you please dig up your explanation of why life has been on the planet evolving for 3.5 billion years but hasn’t died out from GE yet? Ducking the question doesn’t make you look particular interested in honest scientific discussion, ya know?
Ah yes, so not only introns, but ERVs, Alus, other SINES, other repetitive elements. Tremendous opportunities for simulataneous CO-regulation of genes through molecular machines binding on dispersed and tandem repetitive elements with some fine tuning added via chromatin modifications to make incredible feats of combinatorial regulation. This is the sort of Rube Goldberg coordination and complexity human designers can only dream of making.
Praise be to the Intelligent Designer of Life whose wisdom and knowledge exceeds all the combined engineering and science knowledge on the planet!
So why didn’t you account for that possibility 10 years ago in your exchanges with Stephen Meyer (whom you debated) and Richard Sternberg in 2010?
That possibility is becoming more a reality as we’ve studied the cell more, isn’t it? A lot has happened since 2010, and it favors Meyer’s and Sternberg’s claims, not your’s and Larry Moran’s claims.
It’s a shame the “Intelligent Designer of Life” didn’t make a Creationist honest enough to explain why life hasn’t died out from GE after 3.5 billion years of life on the planet. 
An example of @stcordova’s (and Sternberg’s) math skills:
Typical size of transcription factor binding site = 10 bp.
An enhancer may have several individual binding sites, say 100 bp of this sort of functionality.
Average length of an intron in humans = around 2000 nts.
If an intron has an enhancer (not true for many, maybe most), then the ratio of enhancer function to total intron length is 100/2000.
If one tracks back in the discussion @stcordova links to and looks up Sternberg’s assertion about the amount of intron sequences that will possess function, it is around 90%. Thus, in the ID academy, 100/2000 = 0.9.
Go figure.
2 Likes
There he goes again. Sal: non-coding doesn’t mean non-functional and never has. Please learn this simple point.
No, because they will be quotes you have seriously misunderstood or are quote-mining or (likely) both.
1 Like
Finding a region of functional non-coding DNA does not mean all non-coding DNA has function.
How much of the genome is involved in binding these molecular machines? How large are the binding sites, and how many are there?
How many introns bind enhancers, and how much of the intron sequence is necessary for binding?
1 Like
How many of these features bind enhancers or transcription factors? How much of the genome is made up of these functional binding sites? How much of the genome shows deep conservation for these binding sites?
Finding one ERV that has function does not mean all ERVs have function.
1 Like
All the scientists on this site readily agree that there is functional non-coding DNA. What we disagree with is the idea that 100% of non-coding DNA in the human genome has function. Finding tiny bits here and there that have function in no way demonstrates that 100% of the genome is functional.
You are forgetting one very big experiment: comparison of sequences across genomes. 80-90% of the human genome shows no evidence of sequence conservation which is very strong positive evidence for lack of function in those regions.
Finding function in one intron does not mean all introns have function.
1 Like
You have quotes of scientists in 2012 making absolute statements that 0.00% of introns have any kind of functionality? Go for it.
Conserved non-coding DNA is exactly what I work on, trying to identify previously undescribed regulatory regions like enhancers. To suggest that evolutionary biologists are dismissing all non-coding DNA out of hand is to ignore many decades of research. Conserved non-coding DNA is a good mine of regulatory potential and everyone in the field recognises this. Even the non-conserved non-coding DNA isn’t dismissed because obviously there are species-specific functional elements too. Still, the total percentage of the (human) genome with sequence-specific functions seems to be around 10-15%.
3 Likes
That’s a good point. However, there is no reason to think that 80% of the non-coding DNA goes from non-function to functional and back to non-functional over a 1 million year time span.
Since @stcordova linked to a paper that discussed a conserved microRNA, it might be worth discussing this specific example. I have often thought that they could serve as a good example of how evolution and sequence conservation works given their small size and requirements for both secondary structure (i.e. stem-loop) and binding to complementary sequence. If you look at MIR9-2, the microRNA mentioned in @stcordova’s reference, on the UCSC genome browser it sticks out like a sore thumb. You have this <100 bp region with extremely high conservation. How much of the human genome has this strong of a signal? Barely any.
As is evident from this conceptual diagram:
One shouldn’t expect the whole intron to be made of binding sites, the functionality requires some spacing with non-binding sites so that the “arm” created by the intron can actually reach the location. This is like saying the contact point of the screwdriver is only 1% of the screw driver’s volume, therefore the rest of the screwdriver is functionless. Nonsense!
Go figure!
Art said:
then the ratio of enhancer function to total intron length is 100/2000.
You forgot to account for the fact the Topologically Associated Domains are not merely defined by Enhancer regions but by Architectural Proteins as well!
Loops provide functional role, not just the enhancers that occupy a small portion of the loop:
Consider the Topologically Associated Domain (TAD):
The median size of TAD in mouse cells is 880 kb which is found to be similar in non-mammalian species.
This falsify’s Art’s insinuation that function is reducible only to enhancer binding sites!
And here are some of the parts of the loop or things that make loops possible that aren’t enhancer biding regions of the DNA:
So at the very least, Art has to revise his computation just for the binding regions of architectural proteins.
As I said, it’s a naive view to thin the DNA is merely about coding, there is a lot of the DNA that serves as docking areas for molecular machines, and as mentioned above, even the contact area with the molecular machine can’t be considered solely the functional area any more than the end of a screwdriver is the only functional part of the screwdriver.
In 2010, Art debated Stephen Meyer and this led to exchanges on the net with Meyer and Sternberg defending idea that DNA is highly functional and Art, Larry Moran, and Steve Matheson defending the position that DNA is mostly junk.
But that was 10 years ago, and the argument was sort of 1 dimensional in terms of function of sequences.
10 years later, the picture is emerging that we have to consider DNA’s function in 3 dimensions, in fact 4-dimensions, hence the NIH calls it the 4D-nucleome! That’s the difference between then (2010) and now (2020). In 2010 the thinking was 1-dimensional, not 4-dimensional.
The trend of discovery continues to be toward the vindication of Meyer and Sternberg.
This relates to the genetic entropy question because if DNA is more functional than we imagined, then ENCODE is looking to be more right than wrong, and:
If ENCODE is right, evolution is wrong
Because this implies genetic entropy is inevitable at this level of complexity, and Sanford’s hypothesis is correct, or at the very least not overturned.
It is now becoming increasingly clear that cell function, health and fate are correlated to 3D genome folding [25, 45]. TEs are intrinsically linked to 3D organisation as they are “living elements” within a complex multi-scale environment. In the last few years, there have been a handful of studies that started to interrogate how TEs shape genome organisation, from demarcating TAD boundaries [29–31] to harboring binding sites for architectural proteins [34]. It is thus now realized that TEs have profound implications in the fate and health of a cell – not only via the traditional pathway of genomic instability and epigenetic silencing – but also through the global regulation of genome folding.
The pace of discovery is incredible. Even in 2015 when I went to the ENCODE users conference, many suspected TEs had function, but questions lingered. Now it’s a common sentiment they have funciton.
So much has changed in terms of discovery since 2010! Art is defending a viewpoint he stated in 2010 that isn’t consistent with knowledge we now have in 2020.
And that’s why John Sanford’s view is more defensible in 2020 than in 2005 when his book was first published.
1 Like
The rest of the screwdriver isn’t made up of potential screwdriver heads.
1 Like
Most of the sequence of TADs isn’t required for function in any kind of sequence-specific way, meaning it’s not “functional” in any sense relevant to Sanford’s genetic entropy.
The strawman of all strawmen.
It’s not just about coding, junk DNA’s eroding,
with ev’ry knowledge gain
DNA’s n-dimensional, each nucleotide’s intentional…
if I only had a brain
I could while away the hours, computin’ higher powers
And trying to explain
But there’s nowt in my cranium that knows about uranium…
If I only had a brain.
Oh, I could tell you why the beach is near the sea.
I could discourse upon science peacefully.
And cease to dodge genetic entropy.
I would finally be knowin’ ‘bout the diagrams I’m showin’
You’d have no need to complain.
And the jargon I’m misusin’ I’d no longer find confusin’…
If I only had a brain.
6 Likes
Of what, specifically? Does that make all or the majority of introns functional?
How much?