DNA is not just a static read-only memory (ROM) for coding proteins, but hosts dynamic random access memory (RAM) in the form of methylations and histone modifications for regulation of gene expression, cellular differentiation, learning and cognition, and who knows what else. The picture below depicts how rapidly the RAM aspect of DNA is changed during embryogenesis.
Many of the DNA methylation patterns are in non-coding repetitive regions. This suggests at least some of the roles of non-coding DNA are involved in supporting the complex epignomic memory in each cell.
Depicted below are changes in epigenetic methylation marks on the DNA in the stages of embryo development. The light green colors indicate epigenetic methylations and the darker blue colors indicate absence of epigenetic methylations. In boxes “a” through “l”, the bottom part is the DNA from the mother and the top part is the DNA from the father. Eventually the DNA from mom and dad mix in the 4 cells of box “m”.
Note how the epigenetic marks are erased from the parternal DNA first!
The depiction below shows how rapidly epigenetic changes happen even in time frames as short as hours. Each cell has a slightly different methylation pattern and hence each cell’s RAM has some unique information. If we consider that the human has 100 trillion cells and that each cell has 30 million potential methylation sites, the sum total of RAM memory implemented by epigenetic cytosine methylation alone is on the order of sextillions of bits of Shannon information. Like histones, DNA methylations can be written, erased and read.
When scientists inhibit epigenetic changes, the results are usually lethal. So we know the epigenetic component of the DNA is vital to life.
a–e, Anti-5-methylcytosine (MeC) immunofluorescence of mouse one-cell embryos. a, Zygote 3 h after fertilization with intense MeC labelling of both pronuclei (>10). Numbers in parentheses indicate the number of embryos analysed. b Paternal and maternal pronuclei at 6 h (>10). c, Undermethylated paternal pronucleus at 8 h (>20). The smaller female pronucleus remains methylated. d, Aphidicolin-treated one-cell embryo displaying demethylation of the male pronucleus (>20). e, First metaphase (>5). f–j, Controls. Anti-DNA immunofluorescence of one-cell embryos demonstrates that both chromatin sets are accessible to antibody molecules. f, 3 h (>5). g, 6 h (>5). h, 8 h (>5). i, Aphidicolin treatment (>5). j, First metaphase (2). k,l, MeC staining of two-cell embryos at 22 h (>20) (k) and 32 h (>20) (l) shows that the paternal and maternal compartments have different methylation levels. m, Four-cell embryo at 45 h (>10). The MeC-staining intensity of the maternal half of the nucleus is weaker than in two-cell embryos. Scale bar, 10 mum.
http://www.nature.com/nature/journal/v403/n6769/fig_tab/403501b0_F1.html#figure-title
http://www.nature.com/nature/journal/v403/n6769/fig_tab/403501b0_ft.html
Allan –
… it might be helpful in our exchange if we identified all the instances of when exactly epigenetic erasure/rewriting actually occurs; I mean besides gender specific resets during gamete formation by PGC and what appear to be maternal-specific resets immediately following fertilization.
I am wondering if this is where my thinking remains somewhat fuzzy.
Great! Prove it!
Answer the Hinny/Mule question.
• Remember, your answer has to be different than Allan’s because you said repeatedly that Allan was “wrong”.
• Remember, your answer has to be different than mine because you said repeatedly that I was “wrong”.
• Remember your answer cannot contradict your thesis as stated in the original “OP”
Good Luck with that…
Reminder: I already proved any high school student is up to the task by referring to any high school text (for example the the Kimball online test mentioned above) not to mention the University of Utah Learn Genetics links YOU YOURSELF cut & pasted for everyone’s benefit in yet another futile attempt to contradict Allan!
Final Hint Remember – the female hinny and the female mule have exactly identical chromosome/DNA complements and your answer must include some version of the word “erase”.
I await with bated breath your correct answer so I can better educate my own students. I thank you in advance.
Hi again Allan
I will not be near a computer until Monday.
Perhaps you could hold off your answers until Sal redeems himself (or not) on the Hinny/Mule question.
Of course you will realize the Socratic intent of those queries I posed (Sal may not, we will see) and how in fact, we answered them already (again Sal may not, again we will see)
Of course, I posed the questions deliberately as such with a mind to stitch together a brief and focused précis for my own students.
Allan, I have to thank you for helping me out on all this.
best regards as always
TomMueller,
I’d be up for that. I mean, people have all sorts of ideas about how epigenetic markers could be muti-generational, but I see few examples applicable to outcrossing dioecious species.
stcordova,
Of course they are inherited Sal. For precisely one generation. That’s how imprinting works. How many generations does the above effect last? For how many generations can one reasonably expect a maternal methylation pattern on a sequence to survive? (Hint: females have sons. Grandchildren have four grandparents: two male two female).
Your lack of understanding is demonstrated clearly in your initial taunt. Read this post again (or any other), and see if you can find where I say that imprinted methylation is not inherited at all. It would indeed be a bizarre kind of imprint that could not get into a child. How could you even think I would say such a silly thing? I am disappointed!
I doubt you’ll bother/dare, but I would be more than happy for your professors to be introduced to this thread, and adjudicate on my/Jocks/Tom’s understanding vs yours. You game? Yes, I know, busy people yadda yadda yadda.
TomMueller,
Justice demanded a swift answer on a baseless accusation!
Allan Miller,
Indeed. There’s a pattern of sloppy use (and understanding) of language, apparently combined with some pretty impressive wishful thinking, that allows the re-interpretation of any text, whether it’s an abstract or a comment here…
Hey Sal, there’s an Allan Miller who’s published (in Nature, no less) on epigenetic silencing. Wouldn’t it be something if you were (trying to) converse with a published author?
[Allan, hold off…]
a is inherited from A by B
b is inherited from B by C
c is inherited from C by D
Therefore, a is inherited from A by D
Epigenetics by Sal.
DNA_Jock,
Had to peek … First result, an article at UD from 2013: “TSZ Allan Miller says Natural Selection has to fail for evolution to work”. Post by: stcordova.
TSZ Allan Miller says no such frigging thing of course.
On March 24, 2016:
On April 1, 2016
Say what?
I just showed that not all marks are re-established from scratch after all. Ergo, I falsified your claim with actual data. The marks escaped the erasure in Block C of the OP.
You could do the honorable thing and say, “touché” because I’ve won this parry. But, like I’ve observed, you guys are reluctant to ever admit I got something right. 🙂
In case you missed it, this falsifies your insinuation all imprints are started from scratch:
Precisely one generation? Uh, Mother, daughter, grand daughter….conserved in mammalian species?
This. Please this.
stcordova,
Say ‘multiple generations’ is not the same thing as 1 generation. ‘Multiple generations’ has an s on the end.
stcordova,
Not indefinitely. Clearly, a maternally imprinted gene does not remain maternally imprinted in the granddaughter after having passed through her dad. As a female, she must perforce re-establish the marks from scratch when she makes eggs. Likewise any paternal imprint via females. But in fact it doesn’t matter; the marks are indeed demonstrably re-established from scratch either way, each generation, during gametogenesis, irrespective of the gender they end up in next time. Look it up.
And you really can’t see why? I am more than happy to concede error when I err. I haven’t; you are only half-understanding what you read and what I say. Your cocksure bravado is mystifying.
So you have taken a period of the existence of the gene during which meythlation marks are retained, and used that to falsify the assertion (definitely not an insinuation; I actually said it) that methylation marks are not retained indefinitely. And you can’t see a flaw in that logic? Anyway – it is a biological fact that the imprints are re-established from scratch! You see the ERASURE step in the cartoon you claim shows you understood everything all along?
From any individual there is only one purely maternal ancestral lineage, from the 2^g lines that ascend g generations back. So how ‘conserved’ is maternal methylation, even accepting your idea that rewrite=copy, when one bumps into a male ancestor on the backward trail? Or go forwards, same argument.
You misunderstand the usage of the word ‘conserved’, like I said. The authors you picked that word up from weren’t talking about the preservation or repetitiveness of the methylation state at all; they were saying that genes that are methylated (it matters not whether repeatedly or perennially) tend to vary less across taxa than genes that are never methylated.
Like I said Sal, show your professors this thread. I stand by every word I’ve said. I never knew a stick could have so many wrong ends.
ROTFLMAO!
Hey – I will sweeten the pot!
A quick google-whack suggests Sal is badgering hapless university professors at George Mason University… no matter … as long as we are not talking Liberty University or its ilk…
Sal you claim you are possessed of understanding that would greatly benefit my students. I ask you to do the Christian thing and enlighten us – PLEASE! …and assist my students’ understanding.
It’s quite simple really:
Invite your professors to adjudicate (just as Allan suggests) and simply answer the Hinny/Mule question to your professors’ approval.
• Remember, your answer has to be different than Allan’s because you said repeatedly that Allan was “wrong”.
• Remember, your answer has to be different than mine because you said repeatedly that I was “wrong”.
• Remember your answer cannot contradict your own thesis as stated in the original “OP”
🙂
You actually need to provide a mechanism that should refer to at least some of the many diagrams you posted (otherwise why would you have posted them?!)
You must provide a specific mechanism (one will do, more than one also fine)… but you got to do better than
stcordova: The cell as a whole.
To which I already replied:
If you succeed – I publically promise to post on sandwalk.blogspot a declaration of my admiration for you as an intelligent champion of Intelligent Design who is worthy of everybody’s’ respect.
I await my betterment with bated breath! I’ll be back on Monday. I look forward to acknowledging my public debt of gratitude to you.
best regards
Of course, where does ‘a generation’ start and end? By 1 generation, I mean from zygote to zygote. Or gamete to gamete. They are different, but either way there is a transition from 1 organism to another. Imprints do not last across two or more such cycles. They can’t, because of what they represent – gender of parent.
Allan Miller,
Hi Allan,
I suggest we allow Sal to chase his own tail on this and get back to us without any further guidance than we have already provided him.
Talk about the safest bet I ever made!
A safe bet: The sun will rise tomorrow
A safer bet: The sun indeed rose this morning
The safest bet: The one I just made with Sal …
Hey Sal – I will throw you a bone and hopefully save you much effort. Before starting, look up what is meant by “redundancies of propositional logic ”
best
But it’s a multiple generation phenomenon. Why would I say it’s a multiple generations phenomenon? That’s redundant.
Mung,
But imprints don’t get copied across multiple generation.
I was thinking of something a tad earlier…the first guys to characterize a sirtuin gene [PMID:6098447] gave multiple shout-outs to Allan Miller…
🙂
Hi Allan
It’s Monday and no word from Sal, so I shall resume our exchange.
I think you and I are converging on a conceptual asymptote except for one niggling detail:
Allan Miller: If we part paths, it is on the extent to which multigenerational (beyond parent-child) inheritance of epigenetic factors is plausible in a dioecious outcrossing genetic system.
To which I replied:
What you are talking about would be the small number of genes that escape epigenetic erasure/retagging, and these could be the basis of the rare cases of epigenetic inheritance across generations. I consider that maladaptive and possibly some version of an exception that proves the rule.
Clearly such tags can on rare occasion continue across generations:
In Linaria vulgaris
In Drosophila
In rats
In mice
As already cited before and succinctly described here:
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Epigenetics.html
I think where you and I are talking at cross-purposes given those listed exceptions are just that… so-called multi-generational exceptions that do prove the general rule of what we normally call epigenetic marking which includes erasure in PGC and elsewhere (the very complicated story of XIST jumps to mind).
What I am trying to say here is that multi-generational exceptions to the rule are not just not adaptive (this is again where we agree) but in fact may often prove maladaptive (again we agree). So why are we still seeing them? Their presence may offer clues to how “normal” epigenetic tags may be established and maintained. I think you and I are in agreement so far.
The point being much of what we call epigenetics originated (in evolutionary terms) as a defense against the damaging effects of retro elements
This defense was subsequently co-opted as means of gene regulation.
I am guessing some of what we are witnessing in cross generational epigenetic (exception to the rule) terms is the collateral to that retroelement silencing exaptation which is not adaptive for the epigenetic event in question (there you and I agree). We are instead seeing an adaptation for the positive effects of retro element silencing as a whole given the indels caused by retro-elements expression has a much higher potential to produce deleterious effects than positive ones. Those few exceptions cited above may merely represent “collateral damage”. (so sorry – I have been speaking a lot in German lately and am prone to run-on sentences – I tried to fix that)
We have rehashed this all before elsewhere when discussing the “domestication” of parasitic DNA to become symbiotic DNA ultimately generating an expansion of eukaryotic (I am specially thinking Primate) gene regulatory elements; and not just overriding mechanisms of silencing but also overlapping levels of general transcriptional control requiring multiple promoters and enhancers.
Part of the confusion here would be a definition of our terms: what exactly is “epigenetics” and what “epigenetics” is not.
I posed the question:
… it might be helpful in our exchange if we identified all the instances of when exactly epigenetic erasure/rewriting actually occurs; I mean besides gender specific resets during gamete formation by PGC and what appear to be maternal-specific resets immediately following fertilization.
To which you replied:
I’d be up for that. I mean, people have all sorts of ideas about how epigenetic markers could be muti-generational, but I see few examples applicable to outcrossing dioecious species.
I think some lurkers (especially Sal who thought he contradicted you) should read that last sentence over and over again!
I think you nailed it when attempting to explain to Sal the important distinction between inheritance of an epigenetic mark and inheritance of the genetic capacity to establish an epigenetic mark in a parent-of-origin manner …
Or as Lenin once remarked: Весь вопрос — кто кого…?
Bearing in mind as you yourself needed to remind me that sometimes epigenetic tags in fact up-regulate gene expression…
Would it be possible to simplify matters along archaic terminology out of fashion nowadays: the mechanism of “epigenetic tagging” for heterochromatin may differ from the mechanism from “epigenetic tagging” used for “facultative heterochromatin” which may or may not differ from “epigenetic tagging” employed by dispersed euchromatin genes?
Just attempting to refocus our exchange here and come up with something simple enough for my high school students to understand… along the lines of the famous Albert Einstein quipe: “If you can’t explain it to a six year old, you don’t understand it yourself.”
Best regards
To Sal,
I apologize if I was impatient and appeared rude earlier.
I have to give credit where credit is due – you are trying to learn before pronouncing opinion that is informed. Unfortunately, you are failing.
You are also sticking your neck out in public and your courage should be lauded.
Perhaps a conversational reset is in order. If you were more patient with your so-called detractors and did not immediately assume they were incorrect maybe your learning curve would be less steep.
I think you original “Epigenetics as RAM” metaphor is overly naïve!
P Z Myers came up with an excellent metaphor you may appreciate:
“For all you coders out there, it’s like object-oriented programming. When you create a new instance, all the code (the DNA) is the same, but we also have an initiation routine that duplicates all the local variables. “
http://scienceblogs.com/pharyngula/2015/11/18/the-magical-world-of-epigenetics/
ITMT – you really should read what P Z Myers has to say on the subject.
It would appear that cancer has a lot to do with epigenetics which has a lot to do with trans-acting cytoplasmic factors such as miRNA. Again here is P Z Myers:
http://scienceblogs.com/pharyngula/2008/07/22/epigenetics/
and
http://scienceblogs.com/pharyngula/2013/10/12/micrornas-and-cancer/
You may also want to look at this thread, specifically this post:
http://sandwalk.blogspot.ca/2014/03/what-is-epigenetics.html?showComment=1395752770897#c3801031510809553494
TomMueller,
Hi Tom,
I don’t have any problem with seeing epigenetic inheritance across multiple generations (before Sal gets too excited, I restrict that to ‘a couple’) as being in some way accidental. The issues I raised earlier related to not being clear, given the outcrossing 2-gender genetic system, how an adaptive epigenetic response, passing environmental information from one generation down 2 steps, could work. If that’s not on the table, I have nothing to add! Though it would be an interesting pop-gen project, to see if it could be made to work.
One of your references did remind me, via a picture, that the 3rd generation is actually available to be influenced, in mammals at least, by the circumstances of the grandmother. Already, in the developing daughter foetus, the next generation’s germ cells are already approaching maturity. This undermines one, though not all, of my concerns on the multi-generational issue. It’s a maternal-line-only effect though.
I do disagree that anything novel evolved to deal with retro-elements, however.
Hi Allan
If course we agree far more than we disagree!
ITMT If I learned anything from Larry Moran: Most levels of gene regulation are “leaky” explaining why eukaryotes require repeated & redundant fail-safe mechanisms in order to completely shut down inadvertent and inappropriate gene expression that would prove disastrous.
ITMT… A quick rebuttal to your last sentence would be p53, so I suspect I must be misunderstanding you
Here is a tidbit I actually share with my high school students
https://www.sciencedaily.com/releases/2007/11/071114121359.htm
TomMueller,
I don’t think p53 supports the hypothesis that retro-element silencing is the driver behind any given epigenetic mechanism. Bringing genes under the influence of p53 appears to have been caused by retroelement action, rather than having anything to do with novel mechanisms of suppression.
I think the full repertoire of epigenetic systems was well in place very early. To the extent that retroelements needed silencing, the toolkit was, IMO already stocked.
Thanks for the links and conversation.
Look, it might be better not to say whether I do or don’t understand. As I said at Noyau here are the two classes I’m taking at the NIH. The first class was exactly on the interactions of miRNA with P53 with one of the actual NIH researchers of miRNA-34 interaction with P53!
Here is one example:
http://www.ncbi.nlm.nih.gov/pubmed/19221490
Some may or may not characterize ncRNAs as epigenetic, but a rose is a rose by any other name (to quote Shakespeare).
miRNAs come from the DNA and therefore if they are modified they must generally be genetically modified not epigentically modified.
When miRNAs are studied, the engineering done is genetic engineering, not epigenetic engineering. The DNA that generates the miRNA’s is either modified or something else is genetically engineered to over or under express the miRNA or some antago-miR (something to inhibit the action of the miRNA) is used.
Not to be rude, but I’d say the guest lecturer on the topic has priority over PZ Myers — btw that link didn’t even mention miRNA.
and
stcordova,
Sal
1 – The second Myers link is specifically entitled:
microRNAs and cancer
2 – your invocation of ncRNA is most gratifying under the circumstances.
I am delighted you have given up on scoring debating points and have conceded that Ptashne’s thesis has merit.
On the subject of ncRNA, remember that Allan concurred that XIST may be considered “epigenetic”
On the subject of XIST… Well let’s stop there for now
Huh? No.
DNA is necessary but not sufficient.
No cytoplasm, no interactome, no stem cell, no DNA.
Ptaschne cited stuff like this:
Doesn’t work so well if there is no cytoplasm. 🙂
stcordova,
Sal
I feel like I just trapped in a bad rerun of Groundhog Day
Are you telling me that you never even read the paper!? … Yet feel yourself qualified to comment on it!?!?!?!?
Maybe a terrible misunderstanding is happening here and I have misread your post!
Before commenting on Ptashne’s paper; please read it and understand it. As a PNAS publication, it should not be easily dismissed… Or at least it shouldn’t be
So there is no misunderstanding, here it is again
m.pnas.org/content/110/18/7101
I did, where do think I got the references to the factors like Sox3/4?
I feel like such a hinny.
It may be easy to thing the cytoplasm isn’t critical because we can perturb it or fragment pieces of it off, and the cell repairs itself. Hence it is easy to think if one piece of cytplasm is disposable and replenishable, then it isn’t as critical as DNA where sometime even a single nucleotide difference could be devastating.
But that is only a perception. It could just as well mean the cytoplasm is substantially more robust and immune to damage than the DNA. The absolutely wrong interpretation is the cytoplasm isn’t of major importance to cellular function as the DNA. It is only less sensitive to adverse perturbation and damage than DNA. In otherwords, it may be substantially more robust and fault tolerant than DNA, it doesn’t mean it is disposable or doesn’t play a central role in the workings of living things.
Blood cells in humans don’t have DNA. We’d be dead without blood, but the blood cells have no DNA. That tells me we can’t undervalue the importance of the cytoplasm in the functioning of life.
It is also misleading to think “DNA can lead to cytoplasmic changes but rarely do cytoplasmic changes lead to the same radical impact on DNA, therefore DNA is more important.”
Well, that is a consequence of biased sampling. If one sufficiently damages the cytoplasm or cytoplasmic functions, one might not even have any more DNA because the cell would be dead and hence no DNA!
Integration of new genes into cytoplasm is also not a given. We see this all the time with re-engineered E. Coli that expresses human genes but to almost no consequence to the cytoplasmic structure of E. Coli except for the new stuff floating around with no function — like E. Coli expressing human insulin. How can E. Coli get to use a new gene like insulin? Uh, re-engineer the cytoplasm — but that is beyond any technology we could ever conceive of today.
When we do genetic engineering by implanting new DNA in an old style host, the new generations of cytoplasm are changed. But we cannot achieve the converse (i.e. put DNA in cell with different corresponding proteins, and the proteins won’t change the DNA of the next generation, but rather the reverse, the DNA changes the proteins of the next generation.) That is the central dogma.
But changing the proteins in the cytoplasm is different than changing the interactome template. We wouldn’t know where to being to do something like that.
First off, let me make it clear that both Tom and Allan are a) both far more up to date of these issues than I and b) have thought about these issues more carefully than I. All I can do is offer the outdated prejudices of a former yeast molecular biologist.
IMHO, I think there’s an awful lot of agreement here, and the disagreements, such as they are, are at the more speculative “How did this arise?” “Might this be a spandrel?” end of the spectrum.
Tom, to Allan
Abso-effing-lutely!
In a related problem, Sal’s somewhat sloppy use of language seems to me to conflate the issue of ‘inheritance’ of a pattern (of methylation, acetylation, or transcription) during mitosis, and the inheritance of a pattern across generations, particularly the multiple generations required for NS to take hold.
Tom, quoting Allan :
If I understand Allan’s point, then
What would be the requirements for such a system to be selected effectively?
Most of the time, one would expect a boring, short term, environmental effect on gene expression to be a more likely mechanism for achieving the desired plasticity, and multi-generational correlations of environments be damned. OTOH, “anticipating” and “preparing for” a population bottleneck could be a pretty damn nifty thing to do.
As to the origin of heterochromatin, it’s as old as yeast, where the retroposon’s seem to have an eminently sensible gentleman’s agreement to NOT disturb the host’s genes, which is achieved either by inserting upstream of pol III promoters or (as I learnt today) specifically targeting heterochromatin (Ty5). Which might explain why retro-transposed genes are over-represented amongst imprinted genes. Or not…
So from my ancient mol biol perspective, wrapping up whole regions of your DNA when they are not needed is a good way to mitigate the large genome low site occupancy problem for transcription factors. It does also protect them from unwanted recombination events.
But once we get into dioecious species, all sorts of other rationales may come into play, therians, even more.
stcordova,
Sal,
I am dumbfounded! I cannot begin to express my amazement!
I have done my best to be patient – but I give up.
I think Mark Twain may once have opined:
“Never wrestle with a pig: you get dirty and the pig enjoys it?”
Sal – I am about to put you on “IGNORE”. I have never done that before, first time ever.
Before I go, I just want to point out you that since you have started, your position has come around a full 540 degrees and there is no more keeping tack of what you are actually trying to say!
If you ever get around to answering the hinny/mule question, have one of the moderators alert me… that or when you ask your professors to weigh in and adjudicate.
I’m done!
DNA_Jock,
Hi DNA_Jock
I think you have identified exactly where Allan and I part paths:
On an earlier thread I opined along the lines of HumanPrimate evolution
…is essentially a saga of subduing and eventually co-opting Retrotransposons/Retroviruse Jumping as a means of gene regulation.
That said mobile elements directly can still cause three kinds of problems as far as I understand so far… (and please understand that my understanding is far from complete!):
1. A functional gene is interrupted and no longer functional
2. A second copy of a gene is relocated to a different region of DNA, perhaps even a different chromosome. Expression of this gene is now subject to different regulation due to its new location creating all sorts of potential problems including gene dosage effects.
3. The transposition (especially the terminal repeats) may include enhancers which now activate neighboring genes inappropriately.
Mobile elements indirectly contribute to two kinds of other kinds of genetic disorder commonly clumped together as “indel”s, separately considered as inversion and deletion events. Actually, mobile elements can also contribute to a third type of genetic disorder called translocations.
Of course, everything that was identified as potentially problematic is also potential grist for evolution’s mill. Retroelements are undoubtedly the origin of introns and multiple promoters and enhancers in eukaryotes.
Yes, and to belay any nitpicking – the “in” in “indel” stands for “insertion” as in bullet #1 listed above and not “inversion”, even though both are technically equivalent from a Retroelement’s POV… but John Harshman was right to correct me on an earlier blog; I just wanted to rush through all and potential damage that needed “silencing”. I have not even touched on the illegitimate crossover events that result as a consequence of selfish DNA expansion in the genome.
… so to continue with my admittedly speculative line of conjecture:
When the load of Retroelements or selfish DNA becomes too great, the host is obliged to evolve mechanisms to prevent further spread or even mechanisms to eliminating retroelements all together. This may in part explain part of the c-paradox dilemma what Doolittle deemed to be the genomic equivalent of “clean fill” : useful and technically functional but not along the lines ENCODE over-hyped with their findings. “Along the lines…”?!?! hmm a lame pun actually.
Your answer above touched on both constitutive HC (i.e Centromeric and telomeric regions) as well as facultative HC which in fact is interspersed (but not exclusively) with Alu & LINEs (a subclass of selfish DNA) as well as (and this is the important bit) functional genes.
It would appear that the host has co-opted a defense against selfish DNA as a means of gene regulation. Shutting down what once was pesky selfish DNA (those LINEs etc) has become a means of shutting down entire domains of chromatin and may constitute the major mechanism of cell differentiation where entire categories of genes are completely silenced.
Meanwhile, different species have seem to have evolved identical defenses against their equivalent versions of Alu & LINEs thereby obviating the need for conservation across species as a criterion of “function. In other words, what was once selfish or parasitic DNA has been co-opted to become symbiotic DNA with respect to gene regulation all as an exquisite paradigm of convergent evolution.
I like to think of it as perhaps chromosomes having their equivalent to tertiary and quaternary structure. Otherwise how does one explain constancy of karyotypes across primate lineages unless invoking positive selection? It appears that chromosomes have architecture that is organized into active and inactive domains. Whole domains of DNA can be inactivated by conversion into inactive Heterochromatin nestled towards the interior of the nucleus. Inactive heterochromatin DNA is methylated and tightly wound around acetylated histones.
Check out this neat link:
http://phys.org/news/2013-09-x-shape-true-picture-chromosome-imaging.html
So where do Allan and I differ? Allan (as I understand) doesn’t really disagree very much with my speculative line of conjecture except in detail of timing and perhaps my emphasis of silencing selfish DNA as the sine qua non of subsequent evolution of elaborate and exquisitely redundant mechanisms of eukaryotic gene regulation.
I also love to imagine this parasitic Nucleic Acid dates back to the RNA World whereas Allan being a little more circumspect and sober suggests more recent origins.
Nick Lane’s hypothesis of energy costs of DNA being alleviated by mitochondrial symbiotes opening up new vistas of opportunity for parasitic DNA expansion makes eminently good sense – I concede.
I hope I have not put words into Allan’s mouth.
best
P.s. I admit I have really really gone out on a speculative limb of conjecture here. I welcome correction.
Sal,
You are blithering; I mean, really? “No cytoplasm, no life!”
I encourage you to read and understand this paper, which elucidates the importance of DNA.
I think every sentence in this paragraph is, in fact, wrong. Well, except for the first sentence, which is pure gobbledy-gook.
You never did answer my question from two weeks ago:
Or Tom’s hinny/mule question…
I think I am done too.
ET fix link
Tom,
I remain unconvinced regarding the role transposing DNA in the origin of heterchromatin, whether constitutive or facultative. I’m a yeast guy. I find it easier to look on the transposon/host relationship as a simple parasite/host relationship. Neither party survives the death of the host in this system.
I agree that higher organisms have co-opted all sorts of mechanisms in the ongoing battle, esp. with SINES and LINES, but it is my prejudice that heterchromatin predates this particular battle.
I will note that this question belongs in a category that is insanely difficult to address with confidence “We have two (or more) potentially causative mechanisms; what was, in fact, their relative importance, historically?”
It would appear you and Allan are in the same camp and I represent the outlier.
I confess, I am in way over my head here… Family beckons so I leave a parting gift:
Multilevel selection theory and the evolutionary functions of transposable elements Tyler D.P. Brunet and W. Ford Doolittle
http://gbe.oxfordjournals.org/content/early/2015/08/06/gbe.evv152.full.pdf
best regards
Now we all know why Salvador has me on ignore, lol. Because I would “troll” his threads pointing out how confused they were.
DNA_Jock,
It’s also a good way to ask for trouble, of course. Many of the eukaryotic mechanisms of DNA management relax selection against expansion.
TomMueller,
Early evolution of these things is a complex picture involving sex (serial haploidy/diploidy), energy budget, spatial organisation, competition and levels of selection. As I have said before, you would enjoy Burt and Trivers! They don’t go into origin much, but it’s a fascinating survey of their biology.
stcordova,
Uh, Sal, where does cytoplasm come from? You are describing a developmental, phenotypic matter and confusing it with an evolutionary one. As usual.
It seems to boil down to “the things produced by the DNA are at least as important as the DNA itself”. Well, duh.
Good point. So we may have “written ourselves into a corner”. If only evolution had the capacity to look ahead, then maybe we wouldn’t be having this conversation about junk DNA.
😉
Of course, if evolution had the capacity to look ahead, then maybe we wouldn’t be having this conversation at all.
😮
DNA_Jock,
Aye, it’s an ill wind …
TomMueller,
I too am a fan of multi-level selection. What’s not to like?
DNA_Jock,
Yes, another vote for multi-level selection (though I think ‘species selection’ is stretching things a bit).
DNA_Jock,
Allan Miller,
Hi Allan & DNA_Jock
Again, I am not clear where we are disagreeing.
When the load of Retroelements or selfish DNA becomes too great, the host is obliged to evolve mechanisms to silence parasitic DNA or even mechanisms to eliminate retroelements all together… and as an evolutionary afterthought evolve methods of co-opting selfish DNA for gene regulation.
Meanwhile, illegitimate cross-over poses a real problem for eukaryotes with too much repetitive on every chromosome. Heterochromatin suppression of cross-over would be a good thing, n’est-ce pas?
So far so good?
ITMT, I thought the majority of heterochromatin was due to expansion of selfish DNA or subsequent expansion by accidental slippage during DNA replication.
Before revisiting our mutual admiration for Doolittle, I would like to know what am I missing so far…
TomMueller,
I don’t think this works. We have a large clade, all infested with retroelements. It seems more parsimonious to assume that existing mechanisms are co-opted to silence them, than that they drive new mechanisms repeatedly in every clade so infested. The detail of what needs silencing is lineage specific, but the basic class of mechanism likely to be ancient.
Not if it interferes with error correction mechanisms or proper disjunction in meiosis. Heterochromatin needs to be unwrapped sometimes. It’s those times that provide the opportunity for germline transmission.
I think a central issue is sex. Many selfish genetic elements are effectively sexually transmitted diseases. They thrive on serial diploidy and close approach. It’s not clear when sex arrived, relative to other eukaryote changes, but it is basal to the entire eukaryote clade.
I do not think we disagree! I have no problem with “ancient”!
Reversible protein acetylation together with DNA methylation has also been ascertained in Prokaryotes as a mechanisms of gene regulation.
In any case, scientists are now even discussing how to decode bacterial methylomes to unravel Bacterial Quorum Sensing, the Bacterial Equivalent of “differentiation”.
Meanwhile – the AP teachers forum just only recently touched on the need for differential suppression of COs in heterochromatin while simulataneously allowing CO in Euchromatin; precisely for the exaptive need of “error correction” as you so succinctly phrased it.
ITMT – in broad strokes, my thesis of parasitic DNA being co-opted to symbiotic DNA as stated, remains standing. Meanwhile, while some lineages are better (or maybe just luckier) at eliminating the burden of retroelements all together (or somewhat), other lineages must resort to the more expensive expedient of silencing considerable heftier & bulkier amounts of heterochromatin, as was once parasitic DNA.
best
From the Stem Cell Handbook 2013, the chapter entitled “Quantitative Approaches to Model Pluripotency and Differentiation in Stem Cells”
http://link.springer.com/chapter/10.1007/978-1-4614-7696-2_4?no-access=true
As to the never ending litany of “Sal doesn’t understand”, actually it looks like I was like minded with some pretty smart researchers. Get a load of the diagram! Confirms the OP:
Hahaha!