Forum: Why Does Biostar Cover Questions On Epigenetics, But Not Intelligent Design?
2
gravatar for ugly.betty77
7.1 years ago by
ugly.betty771.0k
United States
ugly.betty771.0k wrote:

In a recent commentary published in Cell, UK biologist Adrian Bird compared epigenetics with Lamarckian evolution. He also presented extensive discussion on why epigenetics is bad science and the claims are hyped up.

http://www.sciencedirect.com/science/article/pii/S0092867413010040

The same sentiment has been echoed by respected biologists including Eric Davidson, Mark Ptashne and numerous others. I posted a comment here along the same line, but another biostar member said it was "a minority opinion".

Dan Graur: A Great Commentary on #ENCODE and #Epigenetics by Adrian Bird

Ptashne: Faddish Stuff: Epigenetics and the Inheritance of Acquired Characteristics

Ptashne, Hobart, Davidson: Questions over the scientific basis of epigenome project

Ptashne: Epigenetics: Core misconcept

Two questions.

i) Epigenetics is junk science pretending as real biology and so is intelligent design. Yet when I search for epigenetics in Biostar, I find 76 hits, but no real hit for intelligent design. Where is the line drawn?

ii) Given that three persons up-voted other member's comment ('minority opinion') against only one for mine in the previous discussion, does that suggest that Davidson, Ptashne and Bird are wrong and should be ignored? Why do journals still continue to publish their commentaries, if they are wrong?

I see the rise of ominous trend like Lysenkoism through popularity of this nuevo-fad of epigenetics.


Edit. The discussion we have below is known as Socratic method of questioning. We tried to answer a question and hopefully learned about epigenetics in the process.

The Socratic method (also known as method of elenchus, elenctic method, or Socratic debate), named after the classical Greek philosopher Socrates, is a form of inquiry and discussion between individuals, based on asking and answering questions to stimulate critical thinking and to illuminate ideas.

So, yes, Socrates was very much in my mind (like a commenter mentioned), because Biostars only allows Q-A format. Thank you all for participating.

One hallmark of Socratic questioning is that typically there is more than one "correct" answer, and more often, no clear answer at all.

The biggest problem with 'epigenetics', as we found through the course of discussion is that the 'term' means many things to many people. With so many definitions, everyone will find a few good and bad papers on the topic.

forum • 9.2k views
ADD COMMENTlink modified 4.5 years ago by mickeymousegames20160 • written 7.1 years ago by ugly.betty771.0k
7

This question doesn't seem like a good fit for Biostars. In fact, it seems like an axe-grindey rant masquerading as a question. I wonder if it should be closed.

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Alex Reynolds31k
2

I think it is fun, we can leave any discussion in the Forum. It is another question wether BioStar supports it very well.

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k
4

BTW, certainly ID and other creationist stuff wouldn't be of big interest here, because creationists can't use BLAST.

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k

Soon they will.

ADD REPLYlink written 3.4 years ago by h.mon31k
3

i) ?? ii) Now four people

ADD REPLYlink written 7.1 years ago by Ben2.0k

and I up-voted your comment. More the merrier :)

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k
2

sorry, but this discussion reminds me of this video game: Socrate Jones http://www.kongregate.com/games/ChiefWakamakamu/socrates-jones-pro-philosopher?acomplete=jones

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Giovanni M Dall'Olio27k

Nonsense! Deer lives in the forest!

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k
2

I think we learned what you think about epigenetics, but I don't think that this is the same as learning about epigenetics.

ADD REPLYlink written 7.1 years ago by Alex Reynolds31k

Well, you at least found out that we can argue in great length about something that has no scientific definition :). Apart from that, nothing I said on epigenetics is my own opinion, but merely quotes from various commentaries published in peer-reviewed journals.

For me, dpryan79's comments are helpful and provides with reading materials. I guess these two papers are relevant.

http://www.biochem.uci.edu/resources/PDFs/Jan28/Alarcon%20et%20al%202004%5B4%5D.pdf

http://www.ncbi.nlm.nih.gov/pubmed/21224411

I do not understand why whether RNAi by itself is 'epigenetics' without playing any role in heritability, but hopefully someone would explain the logic.

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
1

The question is first depending on your definition of Epigenetics, asking for clarification.

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k

This. A lot of discussions like this end up with people just talking past each other because they're talking about different things!

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Devon Ryan97k
1

please don't close a post that seems to get a lot of followups/comments and feedback - some of issues that are mentioned may be valid even if the formulation feels deliberately adversarial

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Istvan Albert ♦♦ 85k
4

Yes you are right, however I closed it because I noticed that no more point can be logically added to the discussion and further answers will be futile:

  • The formally correct answer is my second answer (with respect to question title only)
  • The logical fallacy has been rebutted
  • The style and controversial wording of this specific question has been addressed
  • The arguments for concerns about current usage of the term 'Epigenetics' have been pointed out
  • The vagueness of the term in the usage by betty has been criticised
  • The incomparability of the terms Epigenetics and ID has been pointed out
  • Evidence for the presence of certain types of data which are summarized (by some, say Methylation, RNAi) under Epigenetics have been addressed.
  • My personal motivation for the cited comment and possible motivation for voting have been addressed.
ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Michael Dondrup47k

HA, now your trying to tell us you just wanted teach a lecture in logic (we are mostly strong supporters of logical thinking already, as you might have noticed). However, I doubt that Socrates would have committed a voluntary logical fallacy described by Polarize.

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k

Yeah, epigenetics is a relatively vague concept, constantly changing in part because the term is currently "hot". Does that really surprise you?

ADD REPLYlink written 7.1 years ago by Devon Ryan97k

I don't get it.

from wikipedia: epigenetics is the study of changes in gene expression or cellular phenotype, caused by mechanisms other than changes in the underlying DNA sequence.

Do you have a problem with that definition?

Do you think it unlikely, for example, that changes in methylation can result in changes in gene expression?

ADD REPLYlink written 7.1 years ago by brentp23k

Firstly, the definition is unusually broad and covers everything under sun. For example, if I put few tissues in sunlight and their gene expression is changed through optically-induced mechanism, is that epigenetics?

Secondly, the change in gene expression due to sunlight is caused by light changing the chemical behavior of some photo-sensitive proteins and thus affecting the related pathway. That entire pathway was described by traditional genetics. So, why do we need a new term for something that was covered by some other traditional term?

In an earlier incarnation, 'epigenetics' implied what you wrote provided those changes were heritable. Hence the mention of C. elegans by Michael Dondrup and others. Now wiki says - "some of these changes have been shown to be heritable". Therefore, we are arguing over a word that moved well away from its original definition.

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
10
gravatar for polarise
7.1 years ago by
polarise380
Galway, Ireland
polarise380 wrote:
i) Epigenetics is junk science and so is intelligent design. Yet when I search for epigenetics in Biostar, I find 76 hits, but no real hit for intelligent design. Where is the line drawn?

I think that's a non sequitor. It doesn't follow that ID should be here just because epigenetics is here.

ii) Given that three persons up-voted Michael Dondrup's comment against only one for mine in the previous discussion, does that suggest that Davidson, Ptashne and Bird are wrong and should be ignored? Why do journals still continue to publish their commentaries, if they are wrong?

Whoa! Wait a minute. I see a lot of hasty conclusions being drawn here.

The principal goals of philosophy and science are to find the truth. Finding the truth is not dependent on popular opinion but is very often closely associated with it. It is the strong association between popular opinion and truth that admits popular falsehoods. It is logically possible for the popular opinion to be wrong.

Furthermore, the second question assumes that the first is true ('if they are wrong'), which is obviously false.

The right question should be: what is the evidence to suggest that epigenetics is pseudo-science? This is obviously lead to questions on what defines science anyway...

(I feel like I've just fallen into a trap...)

ADD COMMENTlink written 7.1 years ago by polarise380
2

Upvote for the last sentence. Trying to bring logic to an irrational discussion is noble, but at some point you realize it's mostly a waste of time.

ADD REPLYlink written 7.1 years ago by SES8.4k

"what is the evidence to suggest that epigenetics is pseudo-science?"

Lamarckian theory of evolution has been discredited long time back. The burgeoning field of epigenetics is trying to revive it by claiming that they have molecular evidence, but the supposed proofs are inflated as the Bird paper shows.

So, epigenetics is pseudo-science, because there is little scientific data to support the claims. In contrast, when Darwin presented his theory of evolution, he had extensive evidence but his theory was not accepted for many decades even by well-known biologists.

What does that say about strong association between popular opinion and 'truth'?

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k
11
gravatar for Giovanni M Dall'Olio
7.1 years ago by
London, UK
Giovanni M Dall'Olio27k wrote:

I don't get the logic of your reasoning.

You say that Epigenetics (according to some people) is junk science, and is discussed in Biostar. Thus, assuming that intelligent design is also junk science, we should also discuss it on Biostar.

According to this criteria, we should start discussing about any junk science, including astrology and magic. Why should we do such thing?

By the way, I don't think that Epigenetics is a junk science. It is possible that the results obtained so far are junk (I don't know), but I don't consider it a bad science.

ADD COMMENTlink written 7.1 years ago by Giovanni M Dall'Olio27k

I should have said 'junk science pretending as real biology'. Both epigenetics and ID take us back to pre-Darwinian biology on evolutionary origin of species, one proposed by Lamarck and other proposed by Catholic church.

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k
3
  1. epigenetics doesn't date back to pre-Darwinian biology; Lamarckism does.
  2. ID doesn't take back to pre-Darwinian biology: it's from the 1990s
  3. Even if epigenetics dated back to pre-Darwinian biology, that would not mean that it is bad science.
ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Giovanni M Dall'Olio27k

Both Lamarckian evolution and Catholic church's version of evolution have been discredited. ID is trying to revive church's version of evolution by repackaging it in molecular language, and epigenetics is trying to revive Lamarck/Lysenko's biology in the same way.

So, I do not understand why you would allow epigenetics here, but not ID. You said "It is possible that the results obtained so far are junk (I don't know), but I don't consider it a bad science." for epigenetics, but the same can be said about ID.

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k

"I do not understand why you would allow epigenetics here, but not ID..."

If that is what you meant then your question was phrased in a confusing way...

ADD REPLYlink written 7.1 years ago by polarise380
11
gravatar for Damian Kao
7.1 years ago by
Damian Kao15k
USA
Damian Kao15k wrote:

I don't think the functional aspect of epigenetics is in question. Modifications on DNA that produces some kind of effect is pretty well studied. What some scientist consider bad science in relation to epigenetics is the 'genetic' portion of the term. They claim these modifications aren't inherited, instead are re-established using parental cellular machinery, so they are not genetic.

Most of the questions asking about epigenetic changes on BioStar seem to be dealing with the technicalities in detecting these modifications. Interjecting the question with a non-sequiter discussion about the validity of the inheritance aspect of the term is perhaps not that helpful.

It's an interesting discussion. But perhaps discussing it in BioStar questions is not the best way to get your point across.

ADD COMMENTlink written 7.1 years ago by Damian Kao15k

"I don't think the functional aspect of epigenetics is in question. Modifications on DNA that produces some kind of effect is pretty well studied."

Are you making ENCODE's mistake of taking 'some kind of effect' to 'functional'? Bird paper disputes functional aspects as well especially in developing tissues.

"It's an interesting discussion. But perhaps discussing it in BioStar questions is not the best way to get your point across."

Well, there is a newly published Cell paper on the same topic too :)

I presume the end goal of those asking questions in biostars is to figure out some aspect of biology, and most people here are not technicians trying to fix a small error here and there. If someone asks a pseudo-technical question on intelligent design, will the biostar community stay focused on the technical part or will they challenge his broader philosophy on intelligent design?

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
1

As someone whose original background is in Neuroscience, I have to say that some of the epigenetics literature reminds my of the early fMRI papers. Many of those papers (particularly those done by psychologists, but I'm biased) made silly claims like "the Amygdala is responsible for A", or "dead fish have neuronal activity" (that was actually an excellent critique on the field, but it gives you an idea of the lack of rigor early on), completely ignoring the network nature of the brain. These day, these sorts of papers are often quite good , since many of the experimental kinks have been worked out and people now have an idea how much they can read into the results. I see epigenetics following much of the same trajectory.

At the end of the day, bioinformatics is just one tool in the arsenal. If people over-interpret it, it's their own fault.

ADD REPLYlink written 7.1 years ago by Devon Ryan97k

"Are you making ENCODE's mistake of taking 'some kind of effect' to 'functional'? Bird paper disputes functional aspects as well especially in developing tissues."

The honest answer is I don't really know. I haven't read enough papers in epigenetics to give an educated perspective. But like I said, I do think its an interesting discussion. However, starting the discussion off with a inflammatory post and using flame-baiting words, which kind of lowers the bar already, really do not help your point.

"I presume the end goal of those asking questions in biostars is to figure out some aspect of biology, and most people here are not technicians trying to fix a small error here and there."

Actually I do think BioStar is mainly a technical Q&A site and most people who posts are asking technical questions. The setup of questions with comments doesn't really lend itself to long threaded discussions. ID has a good amount of publicity and thus intellectual baggage. If you ask a technical question on ID, I am sure people will bring up that baggage instead of addressing the technical issue.

ADD REPLYlink written 7.1 years ago by Damian Kao15k
11
gravatar for Michael Dondrup
7.1 years ago by
Bergen, Norway
Michael Dondrup47k wrote:

I just wish to answer the original question title and you must accept this as the correct answer :D

Why Does Biostar Cover Questions on Epigenetics, but not Intelligent Design?

BioStar covers questions that are asked by members of its community, no question on ID has been asked before this. We do not answer questions that have not been asked. If a question on ID would ever be asked we will handle it in that case.

ADD COMMENTlink modified 7.1 years ago • written 7.1 years ago by Michael Dondrup47k
1

This is a good answer, but I don't agree with closing.

Indeed, there are no answers on Intelligent Design because people have not asked questions that would involve both ID and bioinformatics. I think we would be more than happy to answer those as well.

ADD REPLYlink written 7.1 years ago by Istvan Albert ♦♦ 85k
2

Yes, I agree it is a very nice and fun distraction from work

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k

Well, so I hoped ....

ADD REPLYlink written 7.1 years ago by Michael Dondrup47k
10
gravatar for Devon Ryan
7.1 years ago by
Devon Ryan97k
Freiburg, Germany
Devon Ryan97k wrote:

You seem to conflate Bird's very legitimate complaints with the Encode project's sometimes overly hyped results with a general complaint about the very concept of epigenetics. To be sure, the talk of "80% genome function" and some of the other headlines are complete and total BS. That doesn't imply, however, that the field as a whole is BS. The biggest issue with epigenetics that I see is that we have too many people that understand almost exclusively statistics/bioinformatics or biology, and relatively few people comfortable with both. So, you get more statistically inclined people making the "80% of the genome is functional" claim and the more biologically inclined using meaningless analyses.

That there is some meaningful effect of epigenetics is largely not in question (there's enough literature from enough different labs doing RNAi, creating KO mice, or applying drug compounds that there shouldn't be any debate over this). The real question should be how big the effect is. Some people (those Bird complains about) seem to think that the epigenetic effect is very large. I (and it would seem Bird as well), don't buy this. I personally work on epigenetic inheritance and my (as yet unpublished) experiments indicate that the epigenetic contribution to things is meaningful, but quite small (not surprisingly, most changes are lost). In the general human experience, the contribution of epigenetics to human variation is vastly swapped by genetic variation. We're still in the infancy of the epigenetics field, so I expect it'll take a number of years to really separate the wheat from the chaff.

Regarding journals publishing these commentaries, firstly, the commentaries do have a point, as I agreed above. Secondly, journals will generally publish whatever sells print. So, they're happy to publish questionable but headline grabbing epigenetics papers and also commentaries that call these BS. Both generate views and references, which equates to more ad views and more money.

ADD COMMENTlink written 7.1 years ago by Devon Ryan97k

"there's enough literature from enough different labs doing RNAi, creating KO mice, or applying drug compounds that there shouldn't be any debate over this."

Would you please post a link to a few convincing papers? Not a trick question. I like to study them in more detail.

Bird wrote about the inheritance aspect, but even the developmental aspect is questionable. You can check Ptashne's article on that (http://www.pnas.org/content/110/18/7101.full). How do cells retain acquired memory after one cell 'learns' it from the environment?

"The Core Concepts Misconception Curiously, the picture I have just sketched is absent from the Core Concepts article. Rather, it is said, chemical modifications to DNA (e.g., methylation) and to histones—the components of nucleosomes around which DNA is wrapped in higher organisms—drive gene regulation. This obviously cannot be true because the enzymes that impose such modifications lack the essential specificity: All nucleosomes, for example, “look alike,” and so these enzymes would have no way, on their own, of specifying which genes to regulate under any given set of conditions. I ignore DNA methylation in the remainder of this article because its possible role in development remains unclear, and it does not exist in, for example, flies and worms—model organisms the study of which has taught us much of what we know about development. Histone modifications are called “epigenetic” in the Core Concepts article, a word that for years has implied memory (see Epigenetic). This is odd: It is true that some of these modifications are involved in the process of transcription per se—facilitating removal and replacement of nucleosomes as the gene is transcribed, for example (9, 10). And some are needed for certain forms of repression (11). But all attempts to show that such modifications are “copied along with the DNA,” as the article states, have, to my knowledge, failed (12⇓–14). Just as transcription per se is not “remembered” without continual recruitment, so nucleosome modifications decay as enzymes remove them (the way phosphatases remove phosphates put in place on proteins by kinases), or as nucleosomes, which turn over rapidly compared with the duration of a cell cycle, are replaced (15). For example, it is simply not true that once put in place such modifications can, as stated in the Core Concepts article, “lock down forever” expression of a gene (7).

It is true, however, that during the course of development as well as at its final stages, certain genes, once “turned on” by a transiently acting transcription factor, stay on even in the absence of the original activator that triggered expression. But I noted above that activation of transcription quickly decays once the activator is removed or inhibited. And so whence this critical memory effect?"

You wrote - "We're still in the infancy of the epigenetics field, so I expect it'll take a number of years to really separate the wheat from the chaff"

Based on the conceptual arguments made by Ptashne, there is no wheat. Do you think it makes sense to address them before collecting huge amount of data on epigenetics, such as the epigenome project likes to do?

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k
3

Aside from the RNAi example from Michael, the general example in neuroscience would be the apparent role of chromatin modifications in LTP (just search pubmed for "chromatin LTP" for a few). I actually rather like Ptashne's critique of epigenetics in development. I would restate it more as a "cart and horse" problem. In short, we biologists know that molecular signaling is EXTREMELY (read that in 64 point font) important in driving gene regulation and development/differentiation. It would be wholly unsurprising to me if epigenetic changes are more of a simple component of these processes that likely help stabilize things (in some organisms and anyone saying that these epigenetic changes are permanent is kidding themselves). The big problem is those that claim that epigenetic changes are the driving force behind large swaths of biology, rather than being likely just another component of them.

Also, I find the phrase "All nucleosomes ... look alike, and so these enzymes would have no way on their own of specify which genes to regulate" incredibly disingenuous. These same argument could be made about half the signaling cascades out that (how many cascades involve MAPK?) or all transcription factors (yes, this is semi-redundant). The disease I worked on for my Ph.D. involves, in part, up-regulation of PKC activity. There are a HUGE number of PKC targets, so one of my committee members asked the quite reasonable question of, "why might increased PKC activity only affect a subset of its possible targets [thus leading in part to this particular disease phenotype in patients]". The answer, as any real-estate agent can tell you, is "location location location". Ptashne alludes to this in his commentary in respect to transcription factors, but the exact same principals apply to, for example, histone deacetylases and DNA methyltransferases (particularly since epigenetic changes seem to affect DNA accessibility).

I guess it should be somewhat apparent that the epigenetics that I'm talking about isn't exactly the definition that Ptashne et al. are arguing against, so it's quite easy to start talking past each other in these sorts of discussions. I generally view epigenetic changes are highly malleable not highly penetrant.

ADD REPLYlink written 7.1 years ago by Devon Ryan97k

I am a bit lost here. Ptashne is arguing that nucleosomes themselves have no distinguishing chemical feature. The 'location, location, location' you mentioned is the contribution of the underlying genome sequence, isn't it? So aren't you agreeing with him in essence?

If the genome sequence is inherited and all positions with ATGCTGATAG get methylated according to some code, that is one thing. If the methylated genome of parents get transferred to children and continue to maintain methylated state irrespective of underlying DNA sequence, that is another thing.

ADD REPLYlink written 7.1 years ago by ugly.betty771.0k
3

No, location is much more than genomic sequence. Genomic sequence will certainly play a role, but it's also the aggregate of the other bound factors, methylation level, and general 3D structure, not to mention the fact that proteins rarely act alone but typically require a host of chaperones and cofactors in the same spatial-temporal context to work efficiently. These are exactly the same processes that start to yield specificity to transcription factors and any molecular cascade. There's also the fact that nucleosomes themselves have modifications that can make them non-identical (though I suspect this is mostly done indirectly through changing the surrounding chromatin context). So yes, I agree with him for the most part, but disagree that this makes the whole thing bunk for the same reasons that very similar arguments don't negate molecular biology.

If you want to criticize someone who argues that parental methylomes are passed on "as is" and have a direct genetics-like effect, then I'm with you, the odds of that are 0. However, I and others have been collecting data indicating that there can be occasional epigenetic transmission (this will not happen with all sites and can certainly be altered by environmental factors). My main beef is with your seeming total dismissal of the mere idea of epigenetics, based seemingly on criticisms of the most over-interpreted conclusions of the field.

ADD REPLYlink written 7.1 years ago by Devon Ryan97k

Someone got the Nobel Price for the discovery of RNAi in c. elegans not so long ago, but this is surely not relevant either... I am sure you'll google that bit of information out xD

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Michael Dondrup47k
4
gravatar for Michael Dondrup
7.1 years ago by
Bergen, Norway
Michael Dondrup47k wrote:

I think you are taking this way too personal. I believe that the comment was mainly upvoted for its second sentence

 Also, I do not see how this is helpful as an answer to state that the topic is 'non-sense'.

My comment was also the result of trying to improve the level of being helpful or altruistic. I thought that after your coverage of BioStar in your blog homolog.us I thought you'd understand this community better, as well as the relevance of a single admin's opinion (I didn't choose this role even, it just happened, if you trust my opinion you are on your own anyway ;). I may err in this specific regard, so may the majority of votes, but so may also
"Eric Davidson, Mark Ptashne and numerous others".
In addition you did very little to make your point more convincing, except some name-dropping an showing us that you are trying hard to be controversial.

I will not go into detail about the logical fallacy in your proposition because that has been outlined by the other posts.

ADD COMMENTlink written 7.1 years ago by Michael Dondrup47k

Nothing personal, not at all :) You are a great person and very helpful guy here, and I acknowledge that Biostar is a valuable community.

I am trying to interject some relevant biological topics among a large spectrum of software-related questions, and I hope that is ok given that the root of biostar is biology. I disagree with you that I did only name-dropping and did not make my point convincing. I linked to three publications by respected biologists (respected because they wrote text-books on the gene-regulation related topics), and each paper covers all arguments against epigenetics fairly well. I thought cutting-and-pasting from those papers would be unnecessary given that the papers are only one click away.

If you suggest so, I can modify my question/comments with text from those papers to see if any answer really addressed the questions raised on epigenetics by those authors.

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
4
gravatar for oneillkza
7.1 years ago by
oneillkza100
Canada
oneillkza100 wrote:

I'll take the Wikipedia definition of epigenetics: "In biology, and specifically genetics, epigenetics is the study of changes in gene expression or cellular phenotype, caused by mechanisms other than changes in the underlying DNA sequence"

So are you suggesting that Biostars should cease to hold discussion of any bioinformatics techniques dealing with DNA methylation, miRNA, ChIP and transcription factors? And are you honestly asserting that the study of any and all of these is pseudoscience? Because there must be at least tens of thousands of peer reviewed papers opposing that assertion.

ADD COMMENTlink written 7.1 years ago by oneillkza100

Nature wrote - "“Epigenetics is a useful word if you don't know what's going on — if you do, you use something else.” [In an earlier era, religion and superstition held that role :).]

http://www.nature.com/news/2008/081022/full/4551023a.html

"No one denies that epigenetics is fashionable: its usage in PubMed papers increased by more than tenfold between 1997 and 2007. And few deny that epigenetics is important. What they do disagree on is what it is.

"The idea is that there is a clear meaning and that it's being violated by people like me who use it more loosely," says Adrian Bird at the University of Edinburgh, UK. Last year he suggested this as a definition: "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states"3. But this wide-ranging proposal, which takes on-board pretty much every physical indicator of a gene's activity is "preposterously dumb", says Mark Ptashne of Memorial Sloan–Kettering Cancer Center in New York, who has published his own take on the word's usage4. "I've grown to be very careful about using the term," says Bing Ren, who studies gene regulation at the University of California, San Diego.

According to the 'traditional' definition that Ptashne favours, epigenetics describes "a change in the state of expression of a gene that does not involve a mutation, but that is nevertheless inherited in the absence of the signal or event that initiated the change". The classic example is found in a bacteriophage called Lambda, which stays dormant in the genome of generations of cells through inheritance of a regulatory protein. These sort of processes are basic to some of the most pressing questions in biology today: such mechanisms are needed to explain how a single-celled embryo can generate cells that are genetically identical, but express a different array of genes and hence take on different jobs in blood, brain or muscle for generation after generation.

Over the past few years, however, all kinds of processes associated with gene control have been subsumed under the moniker. For example, 'epigenetic' is often used to refer to the chemical modification of histones — proteins that DNA winds around — which is involved in gene regulation. This infuriates those who learned the classical definition; they say it puts these modifications at the heart of development and disease despite scant evidence that they are inherited. "Why did histone marks become epigenetic?" says Kevin Struhl at Harvard Medical School in Boston. "People decided that if they call them that it makes them interesting." Others say that it is not about making things sound important, it is more the lack of any other phrase with which to collectively refer to this type of work.

The word had dual meanings long before the current debate. In the 1940s, Conrad Waddington used it to describe how the genetic information in a 'genotype' manifests itself as a set of characteristics, or 'phenotype'. In 1958, David Nanney at the University of Michigan, Ann Arbor, borrowed the term to describe "messy" inherited phenomena that could not be explained by conventional genetics5. "It was controversial in 1958 and everything died down and it has come alive again," says Nanney. "It took 40 years for epigenetics to become a major word in the vocabulary of modern biology."

“Epigenetics is a useful word if you don't know what's going on — if you do, you use something else.” A lot of money can ride on whether a researcher is, or is not, studying epigenetics: the US National Institutes of Health (NIH) this month started handing out US$190 million as part of its epigenomics initiative and other countries are pouring funding into the area. (The NIH is careful to define the epigenetics it is paying for as including both heritable and non-heritable changes in gene activity, something that Ptashne describes as "a complete joke".) Bird says he remains in favour of a relaxed usage. "Epigenetics is a useful word if you don't know what's going on — if you do, you use something else," he says."

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
1

Nature giveth and Nature taketh away....

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by Michael Dondrup47k

That is a good link. That 2007 edition starts with a commentary from the same Adrian Bird, where he seemed more excited about epigenetics.

http://neuron.illinois.edu/sites/default/files/U3_L7_Supplement_PerceptionsOfEpigenetics.pdf

Still he pointed out a few relevant objections -

"The issue of replicative accuracy is also relevant when considering heritability. DNA synthesis is spectacularly accurate, making only 1 ‘unforced’ error for every 107–108 bases copied13. But DNA methylation has an apparent accuracy of ~96%, which is ~1 error for every 25 methylated sites copied."      The 2013 article linked in the main post shows less enthusiam -

"Although most putative examples of transgenerational epigenetics in animals raise more questions than answers (Daxinger and Whitelaw, 2010), there are a few convincing cases. In particular, molecular mechanism and biological rationale are convincingly combined in the case of environmentally induced epigenetic inheritance in the nematode worm Caenorhabditis elegans. Worms use RNA interference to defend themselves against pathogens and to transmit resistance to their progeny using an RNA-based replication mechanism (Ashe et al., 2012). There is an obvious fitness advantage to passing on acquired immunity to offspring who grow up in the same milieu. Indeed, humans attempt the same thing when mothers produce antibody-rich colostrum in breast milk, thereby bestowing their hard-won immunity to contemporary pathogens on the infant. (This latter form of transgenerational inheritance in the absence of mutation, like the passing on of human language, is not normally classed as epigenetic.)

The satisfying evolutionary rationale that accompanies transgenerational inheritance of immunity is less easy to deduce from other putative examples. Why should acquired obesity, diabetes, or impaired learning and memory be foisted on a new generation (Rando, 2012)? One possibility is that they should not, and we are detecting errors in the systems that normally erase the epigenetic baggage of one parental lifetime before embarking on the next. Fitting with this notion, studies in C. elegans show that epigenetic alterations in gene expression are only passed to the next generation when a protein that strips a chemical mark from chromatin is mutated (Katz et al., 2009). Transgenerational epigenetic inheritance in these mutants may be exemplary, but its corollary is a decline in fertility, ending with collapse of the lineage. One could argue that, except when the selective pressure is very great—as in the case of acquired immunity—organisms strive for a clean epigenetic slate with each generation, and only to the extent that this fails do we detect transgenerational epigenetic inheritance. Despite the shortage of convincing evidence, the idea that the consequences of human life experience are epigenetically transmitted across generations has gained remarkably wide currency."

Overall his comments convey the sense that the field of epigenetics is developing far slower than the claims made about epigenetics.

ADD REPLYlink modified 7.1 years ago • written 7.1 years ago by ugly.betty771.0k
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