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
TomMueller,
Each X locus, then, ignoring chimeras. The point was about whether a gender-associated epigenetic trait needs to be X linked or not.
TomMueller,
Hmmm. C. elegans. If humans had a genetic system consisting of self-fertile hermaphrodites and ‘males’, I might consider my point refuted! Till then, my 4-grandparent point stands, in species that actually possess a genetic system permitting of 4 different grandparents!
Exactly, I never conceded that point and specifically said that X – linkage remained unclear. You asked for a mechanism, and I offered an very tentative and speculative possibility – emphasis on the word possibility.
Well actually Ptashne might possibly be even more reserved than you on this score!
He specifically bemoans how much of what we suppose to be universal strategies in gene regulation may be particular to Ecdysozoa or as Brenner called it: the American vs the European model of development. 😉
The fact remains that indeed a plethora of regulation first found in C. elegans and was later confirmed in a host of other organisms including mammals. I direct your attention to the miRNA story.
I am guessing that history will repeat itself.
The point is: you asked for a mechanism and your request was answered. Now we need to wait and see if Ptashne will be vindicated.
TomMueller,
‘A mechanism’ requires more than pointing to the several obvious control mechanisms that have a possibility of becoming a ‘persistent epigenetic state’ down a single cell line, by replenishment of the control molecule. It needs to integrate with the dynamics of the genetic system.
Epigenetic states can easily persist through cell divisions. There is no discard of half the genetic material, and no incoming stream replenishing it from elsewhere. Meiosis/syngamy, however, puts things in a very different light, even though it too has a replication step and a cytoplasmic component. Sure, it can happen, but I’d like to see it happen in a dioecious outcrossing system.
I don’t dismiss the possibility, I just doubt it. It’s not just the impact of 4-into-1 on transmission, it’s the impact on selection. I think having your chances divided randomly by 4 between mutation and selective evaluation has a huge effect on the likelihood of adaptation acting over such a distance. Population genetics would give some guidance on this.
Allan – I am pretty convinced you missed the whole point:
Epigenetic is by definition not genetic!
What is required here is a ‘toggle-switch’ which is supposed to be adaptive because children typically experience the same conditions as their parents but at the same time allows quick resets along Ptashne’s version of Lambda because ancestral responses would be detrimental if the environments of the progeny and the ancestors were different.
Frankly – I am beginning to agree with you that that the Swedish studies may be distracting and of not much relevance here.
TomMueller,
Hi Allan,
Rereading the entire thread makes me wonder if I owe you an apology. I think we were talking at cross purposes and in fact I missed the whole point of what you were on about…
I need to revisit this all!
TomMueller,
Cheers Tom. Fundamentally, from my pov, if one is talking of adaptation, one must be talking genetic, even if the adaptive effect is via an epigenetic switch passed to a descendant. It’s how that would work that puzzles me, with an exponentially increasing number of separate individuals contributing possible settings of any switch as one increases the number of generations between the ‘detector’ generation and the ‘adaptive response’ generation. I think the potential for adaptation from a given mutation falls off precipitously beyond parent-child in a typical sexual system.
Hi Allan,
Too much distraction and my brain is no longer so nimble:
What is Epigenetics?
Epigenetics can be defined as a change in phenotype that is heritable but does not involve a change in the nucleotide sequence in DNA; that is, a change in genotype.
“Heritable” is not really correct when taking about “Epigenetics”. “Temporarily transferable phenotype” is more like it. That is why “Epigenetic” is hyphenated; “Epigenetic” really is NOT genetic.
I am beginning to wonder whether Epigenetics is actually not very much a big deal!
Here is the important bit on imprinting:
In the sperm, all imprints are erased and rewritten with the paternal pattern – even genes that came from the mother – except when they are not and that too is “epigenetics”
In the eggs, all imprints are erased and rewritten with the maternal pattern – even genes that came from the father– except when they are not and that too is “epigenetics”
What feature is common to both scenarios? Cytoplasm may be dictating imprinting, in means similar (but not identical to) the exclusive maternal cytoplasmic effects of say Shell Coiling in Snails which as you correctly observe is genetically determined. In other words, sperm cytoplasm is capable of erasure and resets no differently than the egg. How would we observe such effects in Snail Coiling for example if both paternal and maternal equivalents of this version of “imprinting” were simultaneously occurring?
I would suggest looking for the snail-coiling equivalent of Prader-Willi and Angelman syndrome. 😉 But that too is a none flyer! I was being too glib and facetious.
I still think the Igf2 similarities to Lambda maintenance of Lysogeny are telling – In fact, many parallels with the Trp Operon also exist. Expression of the Tryptophan Repressor protein is also regulated by its own protein product by a process called “autogenous regulation”. The Trp repressor binds to an operator that precedes the Trp gene itself thereby keeping repressor levels low (about 20-30 molecules per cell!!!) allowing the system to be VERY responsive to Tryptophan fluctuations and in the case of Lanbda, very sensitive to environmental signals.
I think what we are witnessing the eukaryotic equivalent of “autogenous regulation” as extremely fine-tuned by the positive feedback commitment steps described by Ptashne… that’s what my gut tells me. Forgive me for being so stubborn on this.
One thing is certain – Nucleosome Modification is the effect and not the cause of whatever epigenetics is.
Where I am becoming very unclear – is exactly where do we differ. again?!
I really need to reread the thread and do some more research.
From the ENCODE consortium, notice around the line that says H3K27Ac, the graph says:
Sample of ENCODE epigenetic data on UCSD browser
That is an example of what 288 million taxpayer dollars bought us through ENCODE.
That is how difficult it is to glean a single epigenetic mark, a the Acetylation on the 27th residue on Histone 3 is presumably near an enhancer region on the DNA. But it shows tangibly how epigenetic modifications of the genome can be viewed. Note, that is only one of many possible histone modifications (somatic cell epigenetic change)!
I’m not sure, but I think DNase hypersensitivity is believe to have some association to epigenetics, but I have to look into that further. The graph in the above link also highlighted DNase hypersensitivity:
Chromatin remodeling is controlled by epigenetic marks, and thus I think the chromatin accessibility as indicated by DNase hypersensitivity is affected by epigenetics.
One thing I learned recently, DNA from “genetically” unrelated regions are poly-utilized to regulate genetic regions. This can happen within a chromosome, and now even between chromosomes — these are “super enhancer” interactions.
We believe RNAs and epigenetic marks are involved in orchestrating interactions such as depicted below where numerous positions on the DNA in seemingly unrelated regions regulate gene expression:
http://www.nature.com/nrg/journal/v15/n4/images/nrg3663-f5.jpg
The following diagram shows how epigenetic marks on non-coding DNA that seemingly unrelated to a particular gene can regulate gene expression. In fact the results of the 3C/4C/5C/6C/ Hi-C ChiA-PET studies (somewhat affiliated with ENCODE) show these sort of unintuitive relationships between DNA segments.
It is not completely understood how the epigenetic marks on histones are themselves regulated. It is speculated the non-coding RNAs are highly important to managing the histone marks.
That’s why I think the ENCODE guys will prevail in their views vs. Dan Graur.
stcordova,
Oh pretty pretty please!
Repeat what you just said on sandwalk.blogspot.com
Please!
stcordova,
Sal
What amazes me is that you have failed to comprehend that you yourself are contradicting your original thesis and publically affirm that your own metaphor of “RAM” no longer stands… thanks to your own intercessions!
I can only imagine you are cutting & pasting much of this thread as submissions for those university course essays you mentioned you are writing.
Who speculates this, how many non-coding RNAs are important for this, and how much of the genome do those particular RNAs take up?
John Harshman replied
I showed at least one example with the HOTAIR lncRNA and there are 41,000 more are suggested by study by the HOTAIR researchers.
HOTAIR lncRNA is expressed on Chromosome 12, then migrates to Chromosome 2 to effect a histone modification via the a molecular machine such as below.
Look where it says below “ncRNA”, one of the ncRNAs that can recruit the polycomb complex PRC2 (below) is HOTAIR.
HOTAIR helps regulate skin cells and is expressed only below the waist, hence skin cells at the soles of the human foot are different than skin cells on the eyelids. HOTAIR is one of the essential components for this differentiation.
Who knows how many other RNAs are involved? Graur can’t possibly know, he’s in no place to say. All he can do is whine and say “ENCODE researchers are crooks” and the pioneer of ENCODE Ewan Birney is “the scientific equivalent of Saddam Hussein”.
The researchers named the lncRNA HOTAIR because they thought it was a joke that HOTAIR could have functional roles until they actually discovered it did. It took years and fairly sizable research team to elucidate function. And that is just one measly transcript!
When this finding was published, the cell biology community was stunned!
http://www.nature.com/nature/journal/v469/n7330/full/nature09784.html
http://www.nature.com/nature/journal/v469/n7330/images_article/nature09784-f3.2.jpg
I said some of this stuff at sandwalk already. For some strange reason the name of one of my blogs, LiarsForDarwin as my name instead of my actual name or usual handle (stcordova for Salvador T. Cordova).
I don’t worry about what Larry says. My professors have different opinions than Larry as they are the ones who are the pioneers of diagrams like those I’ve shown above. They don’t have time to trifle with Larry, and the funny thing is Cheryl Arroway, a professor at Larry’s own university was part of a major NIH planning discussion on Epitranscriptome E4 project (205 million dollars).
There is another person a Larry’s university who is funded by ENCODE. Does Larry really want to do pick a fight with his own colleagues at his own university like Matthew Lupien?
https://www.genome.gov/Multimedia/Slides/ENCODE2015-ResearchAppsUsers/13_Lupien.pdf
By the way, Sal. Thanks for your time and effort here.
This stuff is fascinating.
Contrary to what Rolf alleges, whoever designed this stuff is light years ahead of the V-8 engine.
Keep it coming. Lots of us here in the audience tuning in.
Hey thanks Steve! Have we met on the net before?
Sal
What part of “bulk DNA” need not be informational, do you not understand?
It would appear that gene regulation can also occur by nucleosome modification – yes that part is clear . But (and this is the important bit) you yourself indicate that process needs to be regulated. So what (in your own words please without cutting and pasting others’ efforts) is responsible for regulating nucleosome modification.
That would bring you closer to answering my hinny/mule question I asked you earlier, but you never got around to answering… even yet!
You really begin to remind me of Microsoft’s Tay AI bot
Don’t know, don’t care as far as the OP is concerned.
The cell as a whole.
I stand on the shoulder’s of giants. What? You don’t like the fact I can provide actual evidence of my claims?
stcordova,
I too think your stuff would be more readable without extensive C&P. It reminds me of Dionisio at UD. He seems to be in the process of filling comments with every known biochemical phenomenon. Provide a link as a courtesy; don’t ask people to wade through swathes of text you didn’t even write.
Of course it’s not the likes of me you wish to appeal to, but the grateful hordes like Steve who assume you must know what you’re talking about (being part way through a course and all). What better way to prove it that a good old gob of C&P?
TomMueller,
I think a bone of contention is the capacity of adaptive response (genetic) to act at a significant generational distance, via any mechanism (including but not restricted to epigenetics).
1) An epigenetic state in one cell can be inherited by the daughter cells through a round of mitosis. Pretty non-controversial. Obviously genes for doing this can become concentrated in the population by selection on the individual.
2) An epigenetic state in one individual can be inherited through a round of meiosis and syngamy. Obviously genes for doing this could become concentrated in the population by selection, if there were an increase in fitness available through it. But they can also be concentrated by drive (The Kin theory of imprinting). We seem to disagree on the merits of the former vs the latter, at least for imprinting.
3) An epigenetic state in one individual could (in theory) be inherited through multiple rounds of meiosis and syngamy. This is the one I struggle with, though you may now agree. Drive (via competition for maternal resource) no longer works, because that competition takes place at the single interface, parent-child. So we are left with selection. But how does fitness in the second generation increase, when there are now 4 (or 6) individuals’ epigenetic states to sift through? This also happens to be the proportion by which the allele’s chances diminish over 2 generations.
Perhaps I should separate out the loci: the gene and its site of epigenetic action. Suppose allele A’ arises that sets an epigenetic state B at another locus that really is useful in certain conditions for a grandchild. But A’ and B are both subject to drift – 75% of the time, the combination is discarded before getting to a given grandchild, and a substantial percentage of the time they are disconnected (via crossover). This substantially dilutes chances when compared to an allele that both exists and acts in the one body.
How much of the genome do those 41,001 lncRNAs take up? Enough to support your claim that most of the genome is functional?
Percentages. Let’s see some percentages.
What makes you think I claim most of the genome is functional, I’ve said I suspect it is but no one knows for sure, certainly not Dan Graur who doesn’t even publish real research like the ENCODE consortium does on the topic.
Then you guys would complain I didn’t back up my claims.
Remember John Harshman not getting it about Histone Modifications — Readers, Writers and Erasers.
The way some of my detractors talk, it’s like their just relaying Larry Moran talking points, whereas I relay actual experimental and observational literature.
Obviously some of my detractors don’t seem to really care about the relevant literature, otherwise I wouldn’t have to be posting again and again the conventional use of terms like epigenetics nor the notion of Readers, Writers, Erasers and the usage of the word MEMORY in mainstream literature to describe epigenetic states.
I shouldn’t have to be posting the fact transcription factors are conventionally viewed as proteins not RNAs, but Tom Mueller keeps insisting that they can be RNAs and you backed him up on that.
Then you and DNA_jock insist imprinting isn’t inherited even though it appears over and over and over again, so much so it is called “conserved”.
John objects to me characterizing the epigenetic marks as implementing memory, even though the term “epigenetic memory” is becoming standard in neuroscience literature. When I show the citations, they just get ignored. If I just said it in my own words, you’d demand citations and then ignore the citations. How do I know, we’re still arguing over the conventional usage of the term “epigenetic”.
The NIH ENCODE and RoadmapEpigenetics project provide the conventional, therefore mainstream usage of these terms.
I don’t read all of your comments in detail, but my impression is that your cut-and-pastes don’t support your claims (whatever those may be). It seems to me that you’re using extensive quotations in lieu of actual argument.
You’re relaying some of the literature but, in my opinion, you’re not putting it in any useful context.
I would find your comments more compelling if you clearly laid out your argument and provided links to any supporting evidence you require. As it stands, it looks like you’re just throwing anything that has some of the words you want at the wall to see what sticks. I could well be wrong, but I can’t be bothered to sift through the chaff to find the wheat.
This is just my personal opinion as one reader. As my youngest says, “You do you.”
Just my impression, you’d rather play with EV and Avida then learn how biological systems actually work.
People are just closing their minds even when I provide relevant literature.
Example!: definition of epigenetics and transcription factors. I cut pasted and linked to conventional usage, and Tom Meuller still contests it.
Example: I use the conventional notion that histones can be written to, erased, and read — but John Harshman contested the usage. When I provided the literature from Nature, John protested and said the publishers should insist on using scare quotes. Pathetic.
Ok Patrick,
Here for the 4th or 5th time a depiction of some of the mechanism of changing epigenetic memory that resides on histones. Even after posting it several times, I still get flak for this diagram. Unlike DNA the epigenetic marks on histones can be changed on the fly — just like RAM.
I provided links earlier that discussed how the histone machinery is Turing complete (aka it therefore must implement RAM).
Do you still insist this is irrelevant to the discussion in light of the fact the OP was talking about RAM in biology?
Do you think it is a stretch to say the epigenome implements RAM? Our ability to learn and remember is tied to the epigenome’s capacity to learn and remember — so much so the term “epigenetic memory” is topic in neuroscience.
The response I’ve gotten to a basic biology discussion (not even about ID) just shows how closed some of the minds are around here to learning something other than Larry Moran type talking points.
I read a lot of biology, but there are plenty of people here with advanced degrees and decades of experience in that area. They’ve got a lot more to share than I do.
I address the claims of intelligent design creationists where I feel I can have the most impact. After all, this is a political battle not a scientific one. There is no scientific support for IDC; the reality-based community in the U.S. needs to focus on keeping this nonsense out of schools and laws.
I understand that you’re frustrated. I’m just saying that your presentation isn’t working for me, as one of many readers. I don’t know what your arguments are and I don’t get the impression that the material you provide would support them if I make the effort to extricate them from the rest of the material in your comments.
You are, of course, free to ignore my input.
Analogies can be pushed too far, and historically creationists are prone to doing so.
And there you do it. The differences between biochemistry and solid-state physics are important. While analogies can indicate possibly interesting areas to investigate, they can also lead one astray.
I never insisted that. My only point was that I have no idea what your argument is because I, personally, find your presentation very difficult to follow.
I think that analogies can be taken too far and become misleading.
That seems a stretch, but I’ll leave it to the professional biologists to address.
It’s possible the resistance you’re seeing is due to other factors over which you have more control, should you choose to exert it.
The present discussion goes beyond ID and creation but touches on the harmful rhetoric by evolutionary biologists are directing at the NIH through people like Dan Graur who call NIH ENCODE researchers crooks (his words, not mine).
This is an example of evolutionary biology being abused in a way that is hindering medical progress. It’s not the creationists and IDists who are complaining about ENCODE and its substantial contribution to biological insight, it is from people like Dan Graur who are self-appointed ambassadors of evolutionary biology. His words are bad for the field of evolutionary biology and for science in general. He’s just making trouble for no good reason.
The discussion of epigenetics relate to the work of the NIH.
Allan – I think you and I are converging on the same asymptote
The whole point of epigenetic modification of gene expression – i.e gene regulation in response to environmental cues is that the organism is responsive to the environment! The state of gene expression can be rewritten during any generation by a new set of environmental conditions.
Except when it doesn’t (eg. those chromosome 15 exceptions) which also are exemplars of epigenetics.
An individual could, for instance, be able to thrive in both feast and famine situations by switching appropriate epigenetic tags on and off. (my so-called toggle switch)
The part where I think you and I may be differing is that the default setting of Famine-mode vs Feast-mode may be transferred from one generation to the next: This is where the ‘toggle’ is supposed to be adaptive because children typically experience the same conditions as their parents.
Bringing me back to the latest Cell
http://tinyurl.com/hr3ew97
I think where we are talking at cross-purposes is that you are asking me for something that by definition cannot exist.
I suggest that SOME of what is called so-called epigenetic states can be inherited through a round of meiosis and syngamy along the lines of erasure and gender specific rewriting as we both agree on.
Whereas OTHER so-called epigenetic states can escape the meiosis and syngamy erasure/rewrite process and proceed according to cytoplasmic determined gene regulation be it protein or miRNA or some other trans-acting regulatory factor which clearly exists and may now have been identified in C elegans.
What is required here is a ‘toggle-switch’ which is supposed to be adaptive because children typically experience the same conditions as their parents but at the same time allows quick resets along Ptashne’s version of Lambda’s autogenous regulation of Lambda because ancestral responses would be detrimental if the environments of the progeny and the ancestors were different.
What about some constitutive trans-generational (i.e more than two generations) epigenetic inheritance? That would maladaptive (and probably a contradiction in terms) and I am beginning to agree with you that any such study may perhaps be observing sticky toggle switches (which I highly doubt) and most probably is nothing but noise.
ITMT, I am also beginning to suspect the notion of “dilution” a very unfortunate distractor and rereading Ptashne, we should never have gone there.
Your thoughts?
The problem, as this comment demonstrates Sal, is that you misrepresent and misinterpret the comments of other posters, I assume due to your ignorance. The same thing happens when you C&P from the literature; many of the abstracts that you quoted actually contain sentences that refute your apparent point. You seen to have skipped over these sentences in order to bold, Dionisio-style, quotations that you (usually erroneously) believe support your case.
Furthermore (and strangely for someone who spends so much time agonizing over nomenclature) your exposition lacks the clarity needed to actually have a conversation…
By contrast, when you do C&P, we laugh that you actually believe you have backed up you claims. In reality, you have demonstrated that you are grasping at straws.
stcordova,
Honestly, I have been through your misunderstanding of the terms I don’t know how many times. Genes are repeatedly imprinted, but the imprint itself does not persist, as it is wiped and only re-established if the gender is the right one. Ergo, the imprint is not inherited. The capacity to re-specify an imprint, however, is.
But when your source talks of differential conservation between imprinted and non-imprinted genes, that’s not even what they mean. They mean they undergo a differential rate of evolution – imprinted genes evolve more slowly.
These are subtle distinctions lost on you in your rush to win at all costs. But hey, you know more than people who have actually finished their courses. Because they are TSZ scum, and you can’t learn a damned thing from them. They speak with forked tongue.
stcordova,
The C&P rarely backs up any claim you have made. Witness your repeated pasting of developmental epigenetic switches in supposed refutation of a point I make about multigenerational issues.
stcordova,
This is bullshit, as far as I can tell. Do you have any evidence of any medical research that was thwarted by the evolutionary stance taken by Dan Graur, Larry Moran et al?
Sal – that’s your answer?! Really!?
“The cell as a whole”
I provide a free-translation service
http://tinyurl.com/zbe5n6g
Excuse me?!
The hinny/mule question has EVERYTHING to do with your original thesis!!!!
Now you “don’t care”?! After so many failed attempts to answer what a high school student can answer!?
I will repeat what others have already made clear, but I will try to be politer.
Sal, you fail to grasp of course that you have on occasion agreed with Allan without realizing it – and then gone on to contradict yourself only to again contradict your contradiction.
Your unimpeded C&P spontaneous free prose sometimes reminds me of Kerouac.
Microsoft’s infamous artificial intelligence (AI) chat bot “Tay” sometimes appears to do a far better job of passing the Turing test than you do!
Seriously – please prove me wrong and attempt to answer the Hinny Mule question – one last time.
TomMueller,
A toggle can only be adaptive – that is, can fix through selection – if conditions change with reasonable frequency, though. Something of a paradox. Like I say, pop genetics needed. I’m not sure what conditions could lead to this switch mechanism (which requires detection and response components, as well as passage of the switch setting) becoming established.
I’d prefer not to think of it as dilution. It’s more Mendelian than that!
I’d ignore cytoplasm, which has to be replenished from the chromosome anyway over a handful of cell generations. The issue is that, over 2 generations, 75% of grandparental chromosomes do not end up in a given grandchild, and any 2-locus system (separate loci of trans factor source and epigenetic result) goes through two chances of separation by crossover (it can be trans acting even if it is cis located, of course). That all interferes quite strongly with selection. It’s even worse when you consider the full components of the system – the environment detection component and the second-generation response need to stay together into the grandchild to benefit too. I see these conditions as very inimical to establishment of such a system in the species as an adaptation.
Hi Allan
You have lost me.
Let’s break this down and see where we disagree:
SOME of what is called so-called epigenetic states can be inherited through a round of meiosis and fertilization along the lines of erasure and gender specific rewriting.
I take it we agree on that so far…
Whereas OTHER so-called epigenetic states can escape this meiosis and fertilization erasure/rewrite process… (Igf2 jumps to mind)
Are we still in agreement?
This is all part & parcel of gene regulation –
Agreed?
And cytoplasmic determined factors controlling gene regulation be it protein or miRNA or some other trans-acting regulatory factor clearly play a role (if not an exclusive role) in both categories of “epigenetics” mentioned above…
Still good?
…and may now have been identified in C elegans.
Where do we part paths? Not whether or not these trans-acting regulatory factors play a role but whether or not they play an exclusive role…?
I understand the terms, I argue you have an idiosyncratic notion of what constitutes inheritance.
Skeletal structure is inherited. If we applied your convention, one would say “skeletal structure isn’t inherited since it is re-established with each generation, what is inherited the capacity to re-specify skeletal structure.”
You want to use that convention, that’s up to you, but you used our differing definitions to say I didn’t understand, which is not true — especially since I’m the one who provided the photo in the OP and pointed out the imprints and other epigenetic marks are erased. You have no reason to say that I didn’t understand since I said in the OP:
It’s hard for me to be more explicit than that.
That said, the following refutes some of what you said that the imprints are always de novo
So even by your definitions, the methyl marks on some imprinted genes are copied and maintained transgenerationally.
stcordova,
No I don’t. I also note that you excised my comment on ‘conservation’, which is a genuine howler on your part.
Copying a gene means that its sequence is ‘inherited’ by both daughter copies. No argument there, surely.
Copying a methylated CpG dimer, such that both copies are methylated CpG dimers, means that the epigenetic state is ‘inherited’, in a very similar manner. I would presume we would agree again.
But if one finds a methylation state that appears only in males (or, conversely, only in females), it (the state) is clearly not being inherited. The gene that generates the methylation state is inherited. Obviously, there is a consistent relationship between gender and methylation state. But to say that this means the methylation state is inherited is to fail to appreciate the genotype-phenotype distinction.
Methylation is a funny one. I’d note that methylcytosine is a parallel molecular species to thymine – really, thymine is methyluridine by the same naming convention. It is partly convention that leads us to consider one part of ‘genotype’ and the other not. Methylation of pyrimidines is at the interface between genotype and phenotype. It happens that thymine is methylated before it is included in the strand, whereas cytosine is methylated and demethylated in situ. Its state is ‘copied’ if the daughter strands have the same methylation state in the CpG dimers. Which can certainly happen, but not for more than 1 generation when we’re looking at an imprint.
As far as ‘inheritance’ of methylation state is concerned, it’s like seeing a photo rendered with a watermark. If the watermark is part of the bitmap, copying the bitmap ‘inherits’ the watermark. But if the watermark is added whenever the photo is viewed (but only on a Mac!), it is not being inherited. There is a significant biological difference between these two mechanisms. You want to understand biology better, try and grasp it, instead of simply digging your heels in.
Yes you posted it, then DNA Jock and I continued to point you back to it, and you continued to deny yourself blue in the face that we were pointing to an 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. And here it is again.
TomMueller,
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.
Allan,
So what do you and DNA_jock have to say in light of this, you just totally ignored it:
So even by your definition of in heritance, these imprints are inherited, ergo your claim methyl marks on imprints aren’t inherited are falsified.
Sorry, apparently yours and DNA_jock’s command of the subject wasn’t as deep as you asserted. The misunderstanding was yours not mine.
Hi Allan –
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.
I am a fan of a great online introductory Biology text.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Epigenetics.html
Here is what it says and I direct your attention to
Some epigenetic changes pass from parents to offspring.
In Linaria vulgaris
In Drosophila
In rats
In mice
a brief discussion of
The Inheritance of Acquired Characteristics?
… where the passing of an environmentally-induced epigenetic change from one generation to the next may or may not qualify as the inheritance of an acquired characteristic.
Kimball also discusses the available evidence in humans:
What about humans?
including the caveats
But,
•These were retrospective studies with their built-in limitations [Link].
•Correlation does not guarantee causation.
•If the initial exposure was to a female, we must see the trait in her greatgrandchildren to qualify.
I agree with Kimball’s conclusion which echoes my earlier remarks about maladaptive “sticky toggle switches”:
In the human fetus (and in mice as well), a massive wave of DNA demethylation occurs in the cells — called primordial germ cells — that will later form sperm and eggs. So how to reconcile this erasure of epigenetic marks with evidence of their persisting from one generation to the next? Perhaps the answer is to be found in the small number of genes that escape demethylation, and these could be the basis of the rare cases of epigenetic inheritance across generations.
Forgive me for pulling off a Sal C&P – but I was attempting to prove a point.
Aside to Sal – some meta-lessons:
• I actually understood what I C&P
• My C&P actually supports my thesis
• This introductory text geared for high school proves that high school students could answer my hinny/mule question which you still have not managed to do
• ITMT – C&Ps can be user friendly with a little effort. Simply C&P the RELEVANT titles and highlights and not the entire block of text. To do so, you will actually need to understand what is relevant and what is not.
Back to Allan:
That leaves one out standing question (two maybe)
The precise mechanism whereby so-called epigenetic states can be inherited through a round of meiosis and fertilization along the lines of erasure and gender specific rewriting,
and
The precise mechanism whereby those OTHER so-called epigenetic states which can escape this meiosis and fertilization erasure/rewrite process and whether they operate under a different mechanism.
Which begs yet another question, whether or not in fact several mechanisms for “epigenetic tagging” exist.
p.s. I am a big fan of John Kimball’s altruistic efforts! In email communication, he indicates he needs to update his text a minimum of a dozen times a month. Remarkable resource really – (hint to some present)
Tom,
What makes you think I don’t understand what I cut and paste. Many of them are exactly the diagrams in my class, and by the way I’m making the grade and have been at top of the class in some exams.
How does my professors’ positive assessment of my understanding square with your negative assessment?
One benefit of the classes was to get reassured I actually did understand the peer-reviewed literature despite what the nay-sayers are saying.
I even caught Allan and DNA_jock on a mistake on the inheritance of methyl marks on imprinted genes. Hehe:
So, what say you now? Methyl marks on imprinted genes inherited or not? Hahaha!
I’m taking two classes taught by a pool of 8 professors taking turns based on specialty. I decided to take the evening classes partly because I’m so fed up being accused of not making attempt to learn. Well I’m learning, and I’m realizing my detractors will robotically say I don’t understand whether I actually do or don’t.