[Here is something I just sent Casey Luskin and friends regarding the ENCODE 2015 conference. Some editorial changes to protect the guilty…]
One thing the ENCODE consortium drove home is that DNA acts like a Dynamic Random Access memory for methylation marks. That is to say, even though the DNA sequence isn’t changed, like computer RAM which isn’t physically removed, it’s electronic state can be modified. The repetitive DNA acts like physical hardware so even if the repetitive sequences aren’t changed, they can still act as memory storage devices for regulatory information. ENCODE collects huge amounts of data on methylation marks during various stages of the cell. This is like trying to take a few snapshots of a computer memory to figure out how Windows 8 works. The complexity of the task is beyond description.
To get a hint of the importance of the methylation marks see:
http://www.nature.com/nature/2015/180215/full/nature14310.html
So it’s just my conjecture, the repetitive DNA is there to act as dynamic store of data. We are fooled into thinking since the sequences don’t change much during an organism’s lifetime that it can’t act as an information processing system since we presume the relevant information is the DNA sequence, when in fact the critical information are the methylation marks.
The repetition is probably important for the organism to recognized the regions and say, “hey, here’s where a lot of RAM is for me to use.” The mistake is thinking the significant information content is in the “ACTG” sequences, it is not, it is in the methylation markings, and that could well be where some serious parts of ontogenic regulatory information is flowing through.
Gruar’s approach is akin to opening up a computer and examining the physical RAM in it and saying, “those VLSI transistors are all identical, look at all that repetition, therefore it’s junk!” What matters is when the computer is up and running and we’re seeing these transistors switching back and forth from 0 to 1. Those zero’s and ones are the DNA methylation marks for regulation (not the repetitive ACTG transistors), and that’s why I suspect Graur is way off mark. It really is too early to tell, I wouldn’t yet go out on limb, but Graur is going out on a limb, and if proven wrong, we can publicly call him on it.
Repetitive sequences are plug and play like computer RAM, and can be subject to some variation. But they need to be there.
Exactly. If you can delete (or break) all five of them, and the shuttle still flies, they are non-functional. If the shuttle needs a back up system, the shuttle crashes – they are still non-functional.
The point you seem to have missed, Sal, is that if a gene can take lots of different sequences and the organism still function, then the exact sequence of that gene can’t matter to the organism. Which means it’s junk – if it has any function, then it’s a function that can be served as easily by one sequence as by many variants.
Which probably means if it’s useful at all, it’s useful as spacer – filler.
Which is possible.
stcordova,
I addressed that. If by chance we had a transposon that was active in some tissues but not in others, we would reasonably expect the zygote to contain the ‘active’ version. We can’t realistically expect a corrupt master copy to produce non-corrupted descendants.
If the zygote contains an active transposon, this would have population-level effects on polymorphy. If we don’t see this, then the transposon is reasonably concluded broken in the zygote too, and not just the tissue. And if it’s broken in the zygote, it’s broken everywhere.
stcordova,
Non-coding is not the same as junk. You really need to take Larry’s course!
Transposable element activity in the human genome
We don’t know hardly anything about anything in biology relative to what we could possible learn over the next thousand years, that’s why it’s unwise for you and Moran to presume there is no function. If avoiding looking in those regions prevents us from curing certain diseases, that would be bad. You and Moran obviously would prefer to conclude there is no chance these regions are important to health. What if you guys are wrong?
I’ve already provided papers and research that hint you guys could be wrong. But in the scheme of things, ENCODE and ROADMAP medical researcher have decided they’re going to look while you and Larry want to just stand on the sideline and say their work is a debacle (to quote Dan Graur).
You and Larry are premature and presumptuous.
stcordova,
Likewise, if people focussed on the all parts of the genome with equal intent, that would be bad, if 90% really were junk (which certainly seems to be the case, from numerous lines of evidence).
Real scientists are open to all suggestions, and don’t close down any avenue. But then again, they don’t have unlimited funds. Research has to be targeted. If there is no association with pathology and no apparent function within a region, why bother with it?
And if a piece of ‘functional junk’ is found, who tends to find it – ‘Darwinists’ or YECs?
Do some actual work then, if you are so sure! Or, you know, stand on the sidelines throwing popcorn for the rest of your life. Up to you really.
As a lot of “junk” probably consists of degraded sequences that once served a function, it’s perfectly possible that in the future we could make ourselves more functional. Maybe we could fix the broken vitamin C gene and we wouldn’t have to eat fruit!
But that doesn’t help your case.
Evolutionary theory doesn’t require that there be junk DNA (if DNA were metabolically expensive, it would tend to be eliminated over time, but it seems that it isn’t), but it it can explain it. And it seems that there is a lot of junk. The onus is on ID to explain it under ID. It’s not particularly a prediction under evolutionary theory.
On the other hand, what is, is that if there is junk, it will be found to contain corrupted versions of genes that have a function in other lineages, bits of virus, and other detritus (redundantly duplicated sequences, for instance, or even entire chromosomes). And of course that’s what it a lot of it turns out to be.
The problem for ID theory is that junk is what the word implies: broken stuff that used to work but which has been replaced with newer stuff.
That’s really the key. Everyone would love to get rich and famous by curing a disease. How can anyone be stupid enough to think there is a bias against looking in promising areas?
This strikes me as the most hilarious aspect of the “Darwinist omerta” idiotrope: pharmaceutical companies don`t give a rat’s ass about the ideological implications of their research programs — they are ruthlessly committed to making money — yet, strangely, they stick with the evolutionary paradigm. Strange, that.
That would not be true if there is redundancy in the genome, and there is in fact redundancy in the genome, hence that viewpoint is not supported, likely wrong.
By functional I mean has utility if only in contingency, not that is actively utilized all the time.
I’m afraid your conjecture isn’t supported empirically, here is an example of lncRNAs appearing mostly in the adult stage:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928180/
That shows there is foresight for the adult stage. You’re making the same mistake Larry is making, extrapolating from miniscule sample sizes and making assumptions that the non-Coding regions must be active in the zygote.
As large as ENCODE is, they only track 150 cell types, and those mostly immortalized cells in the cancerous stage. Even ENCODE and ROADMAP have hardly scratched the surface of the Quadrillion transcriptomes that might be involved in development of an adult human. There is no way Larry can be sure of his claim.
ENCODE researchers every year discover function and roles in non-Coding DNA, and usually it is surprising. Larry is premature. And the fact that ENCODE research keep discovering new roles in places people didn’t suspect indicates a trend that we will discover more.
Usually the GWAS studies will give a providential breakthrough that something is up. Usually the researcher reports, “variation in the intronic and intergenic regions compromises health, we report the regulatory role of these regions….” It’s not going to stop. There is no way Larry can know the non-coding DNA have no function in any of the cells during development. If ENCODE and ROADMAP don’t have the data, surely Larry doesn’t either.
Sal, you aren’t thinking this through.
To repeat:
Yes, that is probably because at least some of that material is duplication, as I said. Until it is broken, it is functional, but redundant. Because it is redundant, when it is broken, it has no ill effect.
Clearly, if the sequence it duplicates also breaks, then it will. And that lineage will tend to die out.
But if only one breaks, the lineage survives. And so that lineage continues to carry the broken duplicate – the junk.
Perfectly explicable in terms of evolutionary theory. Not so explicable in terms of ID, unless your argument is that the Designer gave all living things lots of duplicates so that if something broke, there’d still be spare.
Is that your argument? That the junk is indeed junk, but is made of broken stuff that was originally useful in that it was redundant spare stuff, until it broke?
From Larry’s website,
How does Larry know they are functionless. From this review paper:
Gee Larry, these are TISSUE SPECIFIC, which means you’d have to examine every cell and every tissue in every developmental stage before you can safely say it has no regulatory role! That’s probably in the quadrillions of transcriptomes to search. You’re premature Larry.
How do you know that Larry? Did you look into the quadrillions of human transcriptomes to find it never had a role?
Just like coding regions have degeneracy, so do regulatory regions. Tolerating mutations with no ill effect does not imply they are non functional. Coding regions can tolerate SOME mutations without ill effect because of codon degeneracy, that does not imply the coding regions are non-functional.
The line of reasoning that, “it can be mutated, therefore it is junk” is erroneous. Better to say, “it can be mutated, therefore it has some degree of fault tolerance, and if fault tolerant, it suggests purpose and function.”
GWAS studies for various diseases show there is fault tolerance, but not fault proofness in the non-coding regions.
Even granting that, how is it established that the duplicate has no functional role? There are probably a quadrillion or more transcriptomes through the lifetime of a human, and ENCODE and the rest of the world have examined only a paltry few of them.
In the previous comment, regarding pseudogenes, the supposedly imperfect duplicate actually has a role that wasn’t discovered till later. It’s premature to say something is broken just because one hasn’t seen the context where it actually does something.
What I object to is being so presumptuous about things having no functional role. That rush to conclusion has been embarrassing, and I’ve provided reasons why we should not jump to conclusions because much of the activity of the DNA is cell and development stage specific. The functional role of each of these non-coding regions may only be evident in a few of the quadrillion cells at various developmental stages.
How reasonable is it to extrapolate data from 150 cell lines that ENCODE tracks (with great difficulty I might add) to the quadrillion or more transcriptomes that are expressed in a human lifetime?
As someone who endorses genetic entropy, I think there is junk, but we don’t know where it is. Larry and Graur are being awfully premature.
The OP showed that DNA carries more information than just through the A,C,G, T bases. That makes it possible for DNA, even the highly repetitive ones, to convey lots of information, and in fact it is quite reasonable to say even though the ACGT bases of DNA in each cell of a human are mostly the same, the methylation marks are almost unique in every cell. This fact makes it possible for non-coding DNA to have a substantial role that can only be detected as we examine more and more cells at various developmental stages. We have only scratched the surface. Larry Moran, Dan Graur and the anti-ENCODE crowd are horribly premature in call the ENCODE claims a debacle.
The trends in discovery of function in non-coding DNA look like it will vindicate many of the ENCODE claims. ENCODE researchers too may have been premature in their claims of 80% functionality, but the trend is on their side.
Ken Miller might have to eat his words:
Yeah, and we know the fallacy in assuming that just because the ACGTs repeat that it must not be able to carry large amounts of meaningful information!
The information isn’t in the ACGTs alone, but the epigenetic methylation marks.
By Miller’s reasoning, the repeated patterns in VLSI hardware must imply they can’t carry meaningful information — baloney! The methylation marks on repeated ACGT patterns are so information bearing that there is not the quest for, tada: The Epigenetic Code, or dare I say, codes!
Reversible marks? Like I said in the OP, it’s like readable/writable memory. The repetitive ACGT sequences provide a substrate for this information storage.
So what is the role of repetition? The answer, it is easier to recognize! Bwhaha.
http://www.sciencedirect.com/science/article/pii/S0968000498012250
So Ken Miller has to eat his words. Repetition is a way to emphasize a methylation target. Like I said in the OP:
That is not sound reasoning, Sal.
There are two possible reasons why a thing should be “fault tolerant”, and one of them is because it is junk.
Of course it may serve a purpose for which the sequence is not critical – as I said, it could be useful as spacer, or padding.
And the fact is that we know that some of it WAS once useful and now doesn’t work, because it DOES still work in parallel lineages, the GULO gene being a case in point.
So not fault-tolerant in that case.
I can whack sand with a mallet to little effect. So it’s fault tolerant, and therefore suggests purpose and function. Which of course it does – its purpose is to hold the sea up.
stcordova,
God, you’re hard work! I’m going to start charging you for all these geology and biology lessons.
lncRNAs are not transposons. And the DNA for them exists in the zygote, unless you have evidence to the contrary.
Probably? You mean you are just guessing, right?
Nope. You are conjecturing that, if a transposon is discovered to be broken in (say) a bone cell, it may be unbroken in one of the other tissues. If it is unbroken in one of the other tissues, it must be unbroken in the zygote. So here are the things that must happen in ‘Sal-world’:
1) An active transposon is prevented from transposing in the zygote (for no better reason than that it can avoid leaving a troublesome phylogenetic signal, keeping Sal’s theory afloat).
2) In certain tissue types, it becomes broken (in a consistent manner from individual to individual, and from transposon to transposon) – again, mainly in service of Sal’s theory, since the organism already has a zygotic suppression mechanism. Now it has TWO ways of inactivating a transposon! How elegant!
3) In other tissue types, it both remains both unbroken and unsuppressed.
There is not a shred of evidence for such mechanisms operatiing throughout the transposon load of the genome, and significant evidence against. You need it to happen to 50% of the genome. Someone might notice. Bwa and, indeed, ha.
Allan Miller,
Gnnngg. Typos. Yes, I’ve seen ’em! Can’t edit in this darned browser.
Hey Sal – perfect opportunity for you.
See you there?
I was talking repetitive DNA in general, and if adult expression is true for lncRNA, it’s not a stretch for transposons like L1. A zygote isn’t a neuron cell, and I just pointed out L1 transposons are active in neuron cells. They only just determined it.
stcordova,
We were talking about broken transposons, not regulated ones.
It is a stretch if you propose that there is an intact transposon in tissue A, a consistently broken one in tissue B (from which the genome was sequenced), and an unbroken but inactivated one in the zygote. It is ALSO a stretch if you propose that there is an intact transposon in tissue A, a consistently broken one in tissue B and a broken one in the zygote. Particularly if you propose that this model applies to a substantial fraction of the ‘transposome’, which you would have to if you are trying to ‘de-junk’ transposons. The soma just does not work like that.
Neuron cells are derived from the zygote, so that transposon must be whole in the zygote, and therefore capable of transposing (unless there is some elaborate tissue-specific suppressor). You surely aren’t proposing that ALL L1 transposons – or even a substantial fraction – are active (definitely a stretch given that 99%+ of them are consistently bust in multiple genome copies).
I cross posted this to Larry’s blog:
It’s “butt” of the joke Sal, I’m surprised you don’t know this already.
I appreciate your taking your argument to Sandwalk. I’ll be watching, but I don’t expect much. The post is simply too unfocused. A Gish Trot, rather than a gallop.
“liarsfordarwin”. Way to get people to read you charitably!
As if “stcordova” didn’t already. 😛
Well good luck on your predictions.
Having no evidence, no theory and no mechanism, and lots of conflicting evidence should not discourage you.
I am amused by your celebrating the young Pluto.
His birthday is September 5, 1930.
I mentioned duplication as backup strategy at Sandwalk.
Lo and behold:
http://www.sciencedaily.com/releases/2015/07/150706114123.htm
H/T Denyse
Richard Sternberg pointed out quadruplex DNA:
http://www.evolutionnews.org/2009/05/guy_walks_into_a_bar_and_think020401.html
Well Sal, What percentage of DNA is highly conserved, and where can you find someone like Larry Moran who dismisses highly conserved DNA as non-functional?
The reason Larry says 90 percent of DNA is junk is because that is the percentage that is not conserved.
If I understand the argument correctly, it’s deemed not conserved because it is different from sequences in other species and so it’s assumed that these sequences diverged from a common ancestor in which they were the same.
But that does not tell us that they are not currently under selection.
Do they show a wide variance among different members of the same species?
I posted this at Sandwalk:
http://sandwalk.blogspot.com/2015/07/the-fuzzy-thinking-of-john-parrington_19.html?showComment=1437492413384#c928967426522207001
non-Conservation does not imply non-function. Human have orphan genes, we have non-conserved opposable thumbs. Not a good idea to say non-conservation implies non-function.
Larry replied:
All right, lets see who Larry insinuates don’t understand biochemistry. Here are some of the ENCODE 2015 presenters whom Matzke said aren’t that smart:
http://medicine.yale.edu/neurology/people/chris_cotsapas.profile
and
https://biochem.wisc.edu/faculty/pike
http://www.bidmc.org/Research/Departments/Medicine/Divisions/Endocrinology/Laboratories/RosenLab/Members/EvanRosen.aspx
And this guy is a U Toronto where Larry teaches:
http://utoronto.academia.edu/MathieuLupien
Not too swift of Nick Matzke to label Larry’s fellow faculty as not that smart. Certainly some ENCODE researchers understand biochemistry.
And how about one the ENCODE leaders:
https://en.wikipedia.org/wiki/Ewan_Birney
He studied under James Watson, of Watson-Crick fame? And Nick Matzke says they’re not that smart and Larry says they don’t understand biochemistry?
See! I told you guys the lack of mutational effects on non-coding regions is not evidence they are junk but of robustness and redundancy.
Here are papers that reinforce the view that there is a lot of redundancy in the genome, both coding and non coding:
http://onlinelibrary.wiley.com/doi/10.1002/bies.201400036/epdf
http://www.ncbi.nlm.nih.gov/pubmed/9217155
If you know so much about it and are so interested and are capable or making guesses that come true, why are you studying Physics and not Biology?
I posted this over at Larry’s blog. Not surprisingly, there weren’t any substantive counter arguments:
http://sandwalk.blogspot.com/2015/07/john-parrington-and-c-value-paradox.html?showComment=1437966213310#c3108981460501015803
Why do you suppose that is?
stcordova,
Did you provide a substantive argument?
The mouse eye is (perhaps) an example of pre-existing DNA, accumulated for other reasons, being co-opted for other functions. Evolution is nothing if not a bodger. People make all sorts out of junk. This does not mean it was never really junk. It just stopped being so.
If a race of diurnal mice arises, what do you think will happen to the crystalline function in the eye? What will happen to junk? Will it hang around in case the mice fancy becoming nocturnal again? Or will it hang around because there is no advantage to getting rid?
It is certainly possible that junk fulfils a different function in each organism, but this is not parsimonious. Parsimony is a rule of thumb, not a law of course. But given that the commonest inhabitant of all junk in every species is transpositional sequence that has largely and demonstrably lost its ability to transpose, I’d say that’s a strong common factor. The bulk of most supernumerary DNA appears to be the detritus of periodic flare-ups of transpositional activity against which selection, for all but the most virulent, is weak in eukaryotes.
To be fair, someone asked Sal what percentage of junk DNA has been recruited, and Sal gave the expected Sal response.
I keep stuff in my garage that is occasionally called upon to provide spare parts. But while it is sitting in my garage, it is junk. It is non functional. Both junk and non functional are non-ambiguous terms for stuff that was once in use but is not currently used.
The fact that a small percentage of it may later become useful is not really surprising, but the percentage is small.
Interesting that bats (nocturnal) have less junk than mice. Flying animals generally do have less. Does this mean it serves a useful function in non-flying animals that flyers don’t need?
It might be worth mentioning, in addition to junk DNA being recruited for the mouse eye, DNA in conjunction with histones can be used as some sort of read write memory as stated in the OP, not the least of which is possibly memory of the brain!
https://en.wikipedia.org/wiki/Epigenetics_in_learning_and_memory
As I said in the OP:
So there, that extra DNA might get recruited for brain function. We can maybe even test the hypothesis. Knock out all those repetitive sequences and see if a mammalian brain becomes mush. But already there are hints this will be the case because the L1 LINE transposons which Larry keeps arguing are inactive in the germline turn out to be active in neuron somatic cells.
Larry equivocated the defintion of inactive for germlines with inactive for somatic cells and non-transposition uses. The mouse eye demonstrate L1 LINE transposons can in principle be functional even though they may not jump around in the germline cells. I just demonstrated lots of those L1 LINE transposons are functional even assuming Larry’s claim they are “inactive” in the germline. And if indeed L1 LINE transposons are jumping in somatic cells and/or being used as a memory storage and cognitive mechanism in the brain, Larry and Dan are proven wrong yet again.
As far as what percentage? I don’t know. I said I agreed with Larry there could be some junk and that ID didn’t predict non-coding DNA was functional. I only point out, Larry’s being premature. The functionality of DNA being recruited for optical lensing should be caution to being hasty in declaring DNA being junk.
stcordova,
I have argued this with you before, and you didn’t really follow the argument, but there is a reason for thinking they are inactive – they lack the complete proteins required for transpositional activity in any tissue. You can’t reconstitute broken bits of germline genome in the soma. Development doesn’t work like that. We aren’t ciliates.
If the L1 transposons active in neurons are anything remotely close to the 17% of the germline genome that consists of L1 LINEs, I will eat the hat of everyone at UD, without salt. How many transposons are we talking about?