One often hears the suggestion that the neo-Darwinian view of evolution is on the skids, and that that view will be completely changed—if not overturned—by new biological ideas like modularity, genetic assimilation, evolvability, and epigenetics. Epigenetics in particular (I’ll define it in a moment) has been especially touted as a concept that will revolutionize evolutionary biology.
Call me an old fogey, but I think the idea of epigenetics as a Darwin-destroyer is completely bogus. Although certain discoveries in that area are interesting, and have certainly expanded our notion about how genes work, there is not the slightest evidence that the findings of epigenetics will dispel the main ideas of neo-Darwinism, which include the ideas of evolutionary change via natural selection and genetic drift, the randomness of mutations, the ideas of speciation and common descent, and the gene-centered view of evolution. I’ve explained my views on epigenetics as a revolution in several previous posts, for example here, here, here, and here, but, like the Lernean Hydra, each time you cut off a head of the epigenetic beast, it grows another one.
The latest head appeared in Friday’s Guardian, in a book review written by Peter Forbes; the book is The Epigenetics Revolution by Nessa Carey, and Forbes sees the book as tremendously important, implying that is part of a scientific revolution and explicitly saying that it’s a book that would “make Darwin swoon.” I haven’t read the book, and although it might make Darwin swoon if the old git were to be resurrected, the discoveries of genetics and the mechanism of inheritance itself would make him swoon far more readily. And I know scientific revolutions; scientific revolutions are friends of mine; and believe me, epigenetics is no scientific revolution.
So what is epigenetics? The term is actually used in two different ways. When I was younger, it simply meant “developmental genetics,” that is, the study of the way the DNA code of genes is translated into the bodies and physiologies of organisms. That, of course, was a tremendously important and exciting area, and still is. It involves understanding how genes are turned on and off in different tissues and cells, how different genes interact with each other, and how the products of a one-dimensional sequence of information can build a three-dimensional body. This study has segued into the new field of “evo devo,” which tries to understand the evolutionary basis of developmental genetics. “Evo devo” itself has, of course, led to its own important discoveries, like the presence and conservation of homeobox genes, the use of the same genes over and over again in forming similar but non-homologous traits (e.g., PAX6 in the formation of fly eyes and vertebrate eyes), and the linear arrangement of genes in some organisms (e.g., Drosophila) that correspond to the linear arrangement of body parts they affect.
So developmental genetics, and evo devo, are fascinating areas that produce a stream of surprising discoveries. But they’ve done nothing to alter the going paradigm of neo-Darwinian evolution. It is telling that, for example, Sean Carroll, a famous practitioner of “evo devo” and a popular writer, is a firm adherent to neo-Darwinism. What we learn from these areas is precisely how evolution has acted to sculpt bodies, but it still does so using randomly-generated genetic variation and good old natural selection (and yes, Larry Moran, genetic drift also plays a role). Gene regulation itself is a phenomenon molded by natural selection, and how genes are turned on and off is itself a phenomenon residing in the genes: in the genes that make the DNA or proteins that regulate other genes, and in the many ways that genes evolve (through, for example, the evolution of regulatory regions), to respond to internal “environmental” influences.
The second meaning of “epigenetics” is more recent, and involves actual changes in the DNA itself that are not based on mutational changes in nucleotides, but in environmental modifications of nucleotides—things like methylation of nucleotide bases or changes in DNA-associated proteins like histones—that can temporarily modify genes and affect their actions. I say “temporarily,” because such environmental modification of DNA, while it can be adaptive, is not usually passed on from one generation to the next. For example, we get our genes in pairs—one from mom and one from dad—but they can be differentially “marked” (the technical term is “imprinted”) during the formation of sperm and eggs, and so the copy from dad can act differently from the copy coming from mom. This imprinting is probably due to natural selection: scientists like David Haig have argued that the different and conflicting “interests” of paternal versus maternal genes has, through natural selection, molded the way they are imprinted, allowing them to act in different ways in the embryo. But an “imprinted” gene is reset each generation: the imprinting disappears and has to re-form depending on which sex the gene is in.
As I have argued before, however, imprinting of genes, although a novel and recently-discovered phenomenon, is not a “revolution” in how we view evolution: it is an embellishment that doesn’t overturn the main ideas of neo-Darwinism. And many of the phenomena subsumed by this modern notion of “epigenetics” still evolved by natural selection. Imprinting, after all, is based on changes in DNA that somehow render paternal DNA more (or less) susceptible to modification than maternal DNA. Imprinting has evolved by changes in DNA, even though the modifications of DNA it causes are environmental.
In his review of Carey’s book, Forbes, a science writer, concentrates on the second, “revolutionary” sense of epigenetics:
Genes don’t just issue instructions: they respond to messages coming from other genes, from hormones and from nutritional cues and learning. Much epigenetics revolves around nutrition. If we drink a lot of alcohol an enzyme that metabolises it becomes more active – “upregulated” in the jargon. And similar mechanisms apply to much of our behaviour. The methods by which genes makes these responses often involve very small chemical modifications (usually the addition of a tiny methyl group to one base of DNA). It is almost certain that memory – a classic nurture problem: we learn something and it becomes biologically encoded – involves epigenetics. Once made, epigenetic changes can be very long lasting, which is how our long-term memory is possible.
Why is this “revolutionary?” Because some of the inherited changes of genes appear to be “Lamarckian,” that is, they aren’t really changes in DNA sequence itself, but environmental modifications of DNA that can be passed from one generation to the next. And if such “nongenetic,” environmentally-acquired inheritance were common, that would be a revolution in the way we think about evolution.
So what’s the evidence for this “revolutionary” notion? Forbes simply offers up the same tired old anecdotes I’ve addressed before:
So far, this is instructive and highly promising for medical research, but epigenetics finally reaches that “everything you’ve been told is wrong” moment when it claims that some epigenetic changes are so long-lasting they cover several generations: they can be inherited. This flouts one of biology’s most cherished dogmas – taught to all students – namely that changes acquired during life cannot be passed on – the heresy of Lamarckism.
But the evidence that this can occur in some cases appears to be growing. There are lab experiments with mice and rats in which epigenetic effects on coat colour and obesity can be inherited. More suggestive evidence comes from a vast, unwitting and cruel experiment played out in the second world war. In 1944, during the last months of the war, a Nazi blockade followed by an exceedingly harsh winter led to mass starvation in Holland. This had a huge effect on babies born at the time, and the effects of poor nutrition on the foetus seem to have persisted through subsequent generations.
Well, I won’t flog poor Mr. Forbes with the fact that these are only a few trivial examples of the phenomenon, examples that don’t appear to have any evolutionary importance. Nor will I flog him with the fact that when we can dissect the genetic basis of real adaptations in real organisms, they invariably turn out to rest on changes in DNA sequence, not in environmental and non-DNA-based modifications of nucleotides. Here’s what I said in an earlier post about Oliver Burkeman’s claims that epigenetics has profound implications for evolution (like Forbes, Burkeman is a science journalist):
All I can say to this is: “Profound implications my tuchus!” There are a handful of examples showing that environmentally-induced changes can be passed from one generation to the next. In nearly all of these examples, the changes disappear after one or two generations, so they couldn’t effect permanent evolutionary change. The proponents of epigenesis as an important factor in evolution, like Eva Jablonka and Marion Lamb, always wind up talking about the same tired old examples, like cases of coat color change in mice and flower pattern in toadflax. I am not aware of a single case in which an adaptive change in an organism—or any change that has been fixed in a species—rests on inheritance that is not based on changes in the DNA. (For a refutation of the pro-epigenesis arguments that Jablonka and Lamb make in their 2005 book, see Haig [2007].)
Moreover, some examples of “nongenetic” inheritance that do have adaptive significance, such as differential methylation of paternal versus maternal chromosomes, ultimately rest on changes in DNA that promote that differential methylation. And this “inheritance” lasts only one generation, for the methylation profile is reset in each sex every generation.
In contrast to the very few cases of one- or two-generation inheritance that cause nonadaptive changes in the phenotype stands the very, very large number of studies in which inherited changes within and among species map to the DNA. These include every case of evolutionary response to artificial or human-generated selection, adaptive changes within species (e.g., spiny-ness in sticklebacks), and differences among species in both morphology (e.g., the color differences in fruit flies I study) and reproductive barriers (the many mapping studies of “hybrid sterility” and “hybrid inviability” genes). Burkeman, of course, doesn’t mention these cases: it would ruin his nice story.
If we look just at studies of the inheritance of organismal changes that have evolved over time (and many of these would have detected profound epigenetic effects), the score would be something like this: DNA 757, Epigenesis 0. (I’m just making these numbers up, of course, to make a point.) If we look at all “inherited changes”, regardless of their evolutionary importance, we would have a handful of epigenetic changes versus literally thousands of DNA-based changes. So how can Burkeman say that epigenesis will profoundly revise our view of evolution?
So, Mr. Forbes, our “cherished dogma” of non-Lamarckian inheritance still holds strong, and you’ve done your readers a disservice by implying otherwise. Lamarckism is not a “heresy,” but simply a hypothesis that hasn’t held up, despite legions of evolution-revolutionaries who argue that it flushes neo-Darwinism down the toilet. If “epigenetics” in the second sense is so important in evolution, let us have a list of, say, a hundred adaptations of organisms that evolved in this Larmackian way as opposed to the old, boring, neo-Darwinian way involving inherited changes in DNA sequence.
Forbes can’t produce such a list, because there’s not one. In fact, I can’t think of a single entry for that list.
Science journalists—meh. They’re always trying to argue that Darwin was wrong and that evolution is about to undergo a Kuhnian revolutionary paradigm. But what they really want is readership, and you don’t get readers by writing that the conventional wisdom happens to be correct.
A recent conference opened with two talks that were littered with sweeping claims that there is a gap in what genetics can explain and that epigenetics is the panacea…
In one talk a bit of DNA sequence from the honeybee genome was shown and it was asked: “where is the eusociality in that sequence?”
The next morning, a speaker presented data on innate fear responses that cat odours elicit in mice. The mice come from lab strains that hadn’t seen a cat for hundreds of generations… The epigenetics people were silent.
Perhaps the mice had been reading the Caturday Felid entries on WEIT!
What, if any, impact does epigenetics in the second sense have on selfish gene theory?
Considering that epigenetic changes such as methylation must be orchestrated by genes somewhere else in the genome, which in the case of severe starvation say, arrange for certain genes to be suppressed in order presumably, to help the organism cope better in a more hostile environment, none. Some genes, which have been selected over time for these effects, notice that the world has gone to hell in a hand-cart and make temporary belt-tightening changes to deal with that reality. That these changes in gene expression can last for two to three generations before fading away makes no difference to anything in the selfish gene hypothesis that I can see.
Interestingly it does imply that in our past, severe dearth in the food supply was likely to be an ongoing problem, caused more often by long term climate change than by a short lived weather variations. Considering our species’ genesis in the ongoing ice age this makes sense. Things have often gone bad quite quickly in the last several million years.
I would come to the same conclusion, but I haven’t studied the evidence to justify my position. Presumably under selfish gene theory genes that are methylated by others would be expected ‘fight back’, they would have some mechanism to stop methylisation. I know it’s early days yet.
No, why? They’re still getting replicated, just not expressed.
Oh, good point. *Slaps forehead.
All of the really important differences between organisms is in their development. Development is controlled by epigenetic mechanisms that decide which genes are going to be expressed and how much of it, when and for how long. All of development – and are you going to tell me that in spite of the fact that all mammals share about the same protein codes, that the small differences in those codes is the difference between a man and a mouse? But here’s the difference, in the Dutch Hunger Winter – the population was spared, relief came, supplies came – and within a couple of generations the effect was lost – but in a the real world, red in tooth and claw, continued famine might have enabled those children with an epigenetic predisposition to store fat to survived while others died. Establishing, eventually mutational changes to the protein coding or to the control regions of the genes being controlled might replace the epigenetic changes that up or down-regulate a gene at some time or another. If this is true it does put yield a Lamarkian model, at least to some extent. And the factor of “imprinting” in which either a maternal or a paternal allele will be expressed and the other unexplored (never transcribed) allele never will. This by itself has evolutionary implications which haven’t been explored. My guess is that we do not inherit a set of 20-25 thousand genes – we inherit a life script, the genes only actors – the script written in the epigenetic code, the actors called upon the enter or exeunt as their roles demand at different stages of life; conception through embryo, fetus, baby, toddler, preschool… first grey hair, first senior moment… death of old age. It’s the developmental drama that comes first, not the genes.
It is true that science writers exaggerate the newness or revolutionary nature of any scientific finding – think of all the hype surrounding bogus claims by NASA. It is especially disappointing that they are obsessed with noting any topic in which Darwin was wrong. If any of them read the Origin carefully, they would find MANY things that Darwin got wrong – after all, he was writing the first edition in the 1850s! I wonder if biologists are partly to blame for this because they so frequently refer to modern evolutionary biology as Darwinism (which also makes it seem to be an ideology). The jury is out as to whether transient epigenetic change mediates some important evolutionary changes, but it is simply ridiculous to frame these discoveries as yet another place where Darwin was wrong.
Yes – I am sure Darwin himself would never have expected all his ideas or speculations to stand the test of time, but of course the most important one did.
Can you give an example of a biologist referring to modern evolutionary biology as “Darwinism”? Because I’ve only heard that from creationists. It’s one of the red flags that you’re dealing with one, for the very reasons you cite.
A lot British scientists use the term “Darwinist.” Dawkins used to. It isn’t necessarily indicative of a creationist.
Yeah, I hear it being used by more and more non-Creationists. I got mixed feelings about this; while those who use the tools and know the field, seem not to care if it’s being used or not; but the Creationist hears that term, sees a “false idol” and the followers in the camp of this “dogmatic cult” and screams: “Teach the controversy!”.
For an example of a biologist referring to modern evolutionary theory as “neo-Darwinism”, see here: http://whyevolutionistrue.wordpress.com/2011/08/21/is-epigenetics-a-revolution-in-evolution/#comments
Predictably, I’m with you until the line, “Science journalists – meh.” Overgeneralize much?
For the record, in my 12 years at the Tribune, none of us ever claimed Darwin was wrong, Kuhnian upheaval awaited, etc. The closest I came was a pg 1 story back in ’98 about Sue Lindquist’s work on heat shock proteins, but the most we claimed there was that it could help explain how species transition from period of stasis to periods of environmentally-driven change. To their credit, I don’t think the NYT falls for the Darwin is falling! crap either.
Biologists – meh. 😉
Whoops! My bad, Jeremy. Yes, I know you never did that, and neither do many good science journalists, like Carl Zimmer. Clearly I was overreacting in the heat of the moment, and didn’t mean to tar all of you.
However, where are the journalists who write that the fracas about epigenetics is overblown? 🙂
And yes, some biologists are meh, too, including those who write endless books and papers about the overlooked importance of epigenetics!
I do think that you have a point though, but I think these days a lot of spin gets put onto ‘new’ discoveries because publicity can help funding. This could be down to the scientists but also down to administrators in universities perhaps. Sometimes people get carried away by events. Just recall the Darwinius ‘changes everything’ episode. This week the star story is Neanderthal/human ‘hybrid vigour’ –
http://www.telegraph.co.uk/science/science-news/8714018/Scientists-reveal-health-benefits-of-breeding-with-Neanderthals.html
but I am not implying this is hyped – I cannot judge that not being an expert. We can all take a considered view on a new science story based on what we know & what standards of evidence are offered, but often that type of analysis is beyond anyone except a niche expert.
Let me see if I can summarize this.
The Lamarckian epigenetics advocates point out that there are environmental factors that can alter DNA and thus gene expression. I don’t think this is at all surprising; after all, hasn’t this been understood for ages as a very common origin for many types of cancers?
But have any of the neo-Lamarckians demonstrated any of these DNA modifications making their way into the germ line?
If so, how is this any different from standard Darwinian mutation? If not…remind me again how the changes are supposed to make it from one generation to the next…?
Cheers,
b&
That’s more or less what I was thinking. Either the methylation patterns are replicated during germ cell division, or they’re not. Seems like it shouldn’t be that hard to find out. If not, then the case for epigenetics as a paradigm-breaker pretty much fails right there, I should think.
I always understood that while sperm are made all the time, the eggs have developed while the female foetus is still in the womb – is the latter still thought to be the case or have I got it all wrong?
Yes you are wrong. Not your fault though, it has only recently been found that ova are produced throughout adult life, the latter-produced ova are more likely to be defective (I found this totally by chance). Interesting effect of aging.
Genome-wide specific CpG methylation patterns are erased and reset during both spermatogenesis and oogenesis, but the system is a little leaky, and at least maternal environment/diet-induced alterations in methylation patterns and gene expression show up in her offspring (at least in mice, and I’m not sure of the data on paternal exposure effects).
If I understand you right, you’re saying that occasionally the methylation pattern is not reset. But this doesn’t answer the question of whether such patterns can be replicated. If not, then I’d expect at most one in four sperm to inherit the pattern of the parent. (Or maybe two out of four get half the parent’s pattern.)
If they are replicated, that doesn’t sound like a leak, since presumably it would require a specific mechanism to carry out the replication.
There are mechanisms for replication of DNA metylation patterns and histone modification patterns, and since DNA and nucleosome replication are semiconservative, patterns of modifications can be replicated from perettal strand templates as well. So, epigenetic modification patterns are heritable at the celular level. This allows for the maintenance of cell identity (i.e. gene expression patterns) during expansion of somatic tissues in development. However, in the germline, zygotic somatic patterns are largely (although not completely) erased, and germline phenotypic identities established with their own patterns of epigenetic marks. It is in the sense that maternal effects can affect this process, and thus the degree of erasure and reestablishment of de novo modification patterns, that it is generationally heritable.
…that’s “methylation” patterns and “parental” strand and “cellular” level.
Exactly. One can see how this level of inheritance can initially confuse science journalists into mistaking a germline transmission of the methylation profile.
Everyone is acting as though DNA methylation was epigenetics. What about the arrangement of chromosome territories in the interphase nucleus, what about the regions of condensed chromatin that are cell-type specific, what about all the the chemical modification of specific histone residues – the meanings of which we know in the simplest cases. And what orchestrates, what directs the remodeling of chromatin that determines cell type? (The cell type of the zygote as well.) Haven’t we always believed that the developmental program is contained in the ‘epigenome’ it is an interaction of genes and the genome behind our developmental program – the ‘script’ is in the epigenome, the proteins the actors (effectors, protein and RNA molecules). Knocking out a CpG island certainly is final for some genes but it may not be the only inherited pattern.
If an organism can pass down ‘learning’ – like the children of the “Hunger Winter” in Holland, to it’s offspring – a very particular kind of ‘learning” as in pro-survival behaviors, then to the horror of “Darwinists” (and in the aging field researchers must practically take an oath to Darwin insisting that aging can’t be programmed nor life span inherited), it might very well be that there is an “intelligent design’ element, nothing supernatural, merely an organism selecting (by what means?) a more advantageous route for the development of its offspring. It may be that the organism by its nature tries to further its offspring by stressing certain traits ‘epigenetically’, can you say otherwise (Certainly the propensity to gain weight of the children of children who had known hunger during their development has been substantiated – isn’t this an example of learning at a very basic level – the body learning to store food in the event of a famine? The existence of this sort of “learning” is not proven, but it would explain many phenomena now unexplained, (for example, the “Flynn Effect” where every generation increases in intelligence, or the fact that the children of immigrants are more likely to fit the physical norms of the country they’re born in then of the country their parents came from even in characteristics such as head shape – not body size which of course depends on nutrition). To deny that this is possible is not science, it is a Darwinian religion and hence antithetical to the true nature of science -a science based solely on evidence as the ultimate arbitrator of opinion and the only justifier of ‘theories’. Now I’m not (as yet) a neo-Lamarkian, but though I do think that Darwin discovered a great and true principle, that doesn’t necessarily mean it’s the only principle or that we understand it completely. I’d at least open my mind to the possibilities.
In aging, in spite of what the neo-Darwinians say (all the “old school” including Hayflick himself)about the “impossibility” of programmed aging, that when you realize (based solely on the evidence) that the wear and tear theory of aging is incorrect (If it were then cells could not be rejuvenated (they would be damaged beyond their ability to repair themselves – by definition). And rejuvenation has been demonstrated using various processes (production of induce pleuripotent cells for adult cells, the cloning of cows using nuclei of senescent cells, cross-age tissue transplantation, parabiosis that – cell, tissues, organs and even organisms have been rejuvenated. Evidence alone made me realize that aging is a programmed process (and all through publications in top ten journals including the 2005 Conboy paper in Nature and the Stuart Chambers paper in PLOS) – that the transcriptional patterns of the different tissue types are age specific; that these middle aged and old cells down regulate the transcription of repair and maintenance systems at a time when the damages those systems were supposed to repair repair increase (coincidence?). If you see the evidence not only will you believe in programmed aging – but you also might see a way around it (hint: if only you could reset the clock of each cell, have every cell go back two acts and one scene in its life-script and start again from there?!!! Well, you know what, it’s already known that you can).
I would like to recommend to other readers ENDLESS FORMS MOST BEAUTIFUL by Sean B. Carroll. It is about EVO DEVO and can be read by anyone.
I second the motion. Great book!
I saw this article at the Guardian and sighed. And I also remembered back to another Guardian piece I read recently:
http://www.guardian.co.uk/commentisfree/2011/jul/24/science-reporting-climate-change-sceptics
“But then the pursuit of truth has always been a tricky and cruel business. “It is true that some things come along like that to throw scientists into a tizz but it doesn’t happen very often,” adds Jones. “The trouble is, the BBC thinks it happens every day.””
Oh, teh irony.
Thanks to Jerry for clarifying that his attack is not on ALL journalists. And let us also consider the first comment in this thread. Who was making those sweeping statements about epigenetics? Scientists, that’s who. Ph.D.-carrying scientists.
Now, I’m not saying that ALL scientists are trying to boost the importance of epigenetics. But it’s not as if scientists aren’t at all involved in this hype.
Hmmm, scientists trying to hype the field they work in, this wouldn’t have anything to do with getting the next round of funding in the bag would it? Surely not.
Hmmm, journalists trying to hype the field they write in, this wouldn’t have anything to do with getting the next round of readers in the bag would it? Surely not.
😉
I thought you would have something to say on this when I read the review.
Thank you for explaining this so clearly, it’s a fascinating read.
Ok, so now it’s all explained and settled and this will be the last we hear of it, right? Right?
!
I did not read the article nor the book itself, and I hope they indeed deserve Jerry’s ire. It is also true that many people in the field are, shall we say, overenthusiastic about epigenetics, probably simply because they find it a concept with exciting and far-reaching potential implications. Still, I would have liked to see Jerry writing about epigenetics more thoughtfully. These days, this word means usually simply “non-genetic inheritance”, that is inheritance of phenotypes through non-genetic means. Despite what Jerry seems to be implying, there is no need for an epigenetic process to subsequently incorporate these phenotypes into the DNA (which is indeed problematic, though it probably does happen sometimes). Thus, for example learning is a vectors of epigenetic inheritance that is of undisputed importance in evolution.
In fact, I have just left a very nice talk by Russell Bonduriansky where he argued the above points very persuasively, and I would suggest to anybody who’d like a more balanced perspective to consult his writings.
http://f1000.com/thefaculty/member/4070946699247260
His home pages would not open for me but there is a link here. Will take a look when I can!
I agree with vHF here, and I’ll add this: I think it’s particularly easy to discount the potential evolutionary importance of epigenetic inheritance when you focus only on animal examples (of which there are few). On the other hand, epigenetic inheritance appears to be much more common in plants and fungi than in animals. It’s unclear exactly why, but it probably has to do with the fact that the germline is derived from somatic tissue late in development in most plants and fungi, whereas the germline is sequestered very early in development in most animals. This increases the likelihood that acquired epigenetic states are passed on to the next generation (coupled with the fact that resetting of methylation marks appears to be less extensive in plants compared to mammals). There are a number of recent studies in plants that should make anyone think very carefully before dismissing epigenetic inheritance as a source of potentially meaningful phenotypic variation. For example, studies on epigenetic recombinant inbred lines (epiRILs) in Arabidopsis show that DNA methylation can generate a vast amount of variation in ecologically important quantitative traits, such as plant height, flowering time, germination timing, and pathogen resistance (see 2009 papers by Reinders, Johannes, and a few others that escape me at the moment). These plants are genetically identical, differ only in DNA methylation status at many sites across the genome, and differential methylation patterns are stably inherited far at least 8 generations. And the epiRILs are just one example. But, I don’t think any of this forces a revolution in biology. We’re talking about selectable variation here, it just doesn’t stem directly from genetic variation. What we need to know now is, how common is epigenetic inheritance outside of the lab and in the field? This is an entirely open question, and it seems reasonable to me to simply withhold judgment on the importance of epigenetic inheritance until that question is answered.
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I’m struggling to understand when something is defined as due to epigenetic factors. Taking the simpler case of “developmental genetics” ~ I take epigenetics to be the study of changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence.
QUESTION. Is my argument & conclusion correct in the below ? :-
In some reptiles the temperature that the eggs experience during the middle third of the incubation period determines the sexes of the organisms that hatch. I assume that the DNA in the male & the female is the same & it is in the expression that the difference lies.
Therefore the sex of some reptiles is determined by epigenetic factors.
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I would say that’s a good use of the term. In the classic sense, any regulation of gene expression (i.e. not just specific covalent DNA and histone modifications) can be considered to be epigenetic, since they control the phenotypic manifestation of the genotype.
Cheers rb ! It’s good to know I’ve found an example on my own. I struggle with the jargon.
Temperature dependent sex determination in reptiles also fits neatly with Dawkins’ recipe metaphor for development (‘bake at 350 F for a male, 375 F for a female’) as an example of epigenesis in the Waddingtonian sense. See http://whyevolutionistrue.wordpress.com/2011/05/14/development-is-epigenetic/
thank you Greg – will go to your link now
I have been following and thinking about this “new revolution” in evolution for a year now. Having read some argument for and against it, I found it to be true in a sense of adding more to our understanding of evolution, which happens all the time, so that is not so much of a revolution. The only thing that I would disagree with Prof.Coyne and Dawkins about is their mystification of the gene, as Prof. Stephen Rose said. Genes are important in evolution – no question about that – but there is more to it than just genes. But Ernst Mayr has explained that before “the new revolution”, so it is just that we now know more about the auto mechanics of evolution, than just Population genetics.
I would disagree that they engender in “mystification of the gene”, it wasn’t until I read some second hand accounts (mostly by themselves) of Dawkins’ and Coyne’s descriptions that I understood how to simplify my earlier confusion.
Of course there are more to cellular life forms than genes, or you could have viable DNA-DNA recombination without cells!
I know, I sometimes read some accounts of both of their perspectives and I think to myself that this description is not a “selfish gene” one. There is a wonderful conversation between Prof.Rose and Prof.Dawkins on youtube, that might illustrate my point. I hope that the future undergraduate textbooks of Biology, will have a more pluralistic view of evolution, than just changes in allele frequency in gene-pools.
“If we drink a lot of alcohol an enzyme that metabolises it becomes more active – “upregulated” in the jargon. And similar mechanisms apply to much of our behaviour. The methods by which genes makes these responses often involve very small chemical modifications (usually the addition of a tiny methyl group to one base of DNA).”
And?
Does it affect alcohol dehydrogenase in the germ line?
Someone should tell him that DNA methylation generally down regulates genes
Well what happens when a tumor suppressor gene that represses an oncogene is hypomethylated in its promoter (functionally silent)?
The important thing I think is that when it comes to a phenotype or trait, gene expression is relative.
In other words, scientifically illiterate morons are reporting stories to the scientifically ignorant masses, and spreading hyperbole? Sounds like any news outlet if you ask me. Most don’t even recognize science, let alone have the ability to report on it…
The more sensationalist journalists such as Forbes remind me of the story of the happy little boy who never saw the negative side of any event. When the psychologist put him a room filled with a pile of horse excrement, he dived into it shouting, “I know there’s a pony in here somewhere!”
It’s science by press release – apparently it gets folks’ work published quicker than via journals.
Could phenotypical changes due to epigenetic factors not lead to reproductive isolation, and thus drive speciation?
Yes. In fact, this is seen in some of the more ‘wild’ mouse lines.
See this paper:
Zechner U, Shi W, Hemberger M, Himmelbauer H, Otto S, Orth A, Kalscheuer V, Fischer U, Elango R, Reis A, Vogel W, Ropers H, Rüschendorf F, Fundele R. 2004.Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus.J Evol Biol.17(2):453-60.
and this one:
Vrana PB, Fossella JA, Matteson P, del Rio T, O’Neill MJ, Tilghman SM. 2000. Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in Peromyscus. Nat Genet.25(1):120-4.
And, an intriguing aspect of DNA methylation is that methylated cytosines are MUCH more likely to become deaminated, which results in cytosine converting to a uracil. This will then be removed and changed to a thymine. The C to T mutation frequency is observed approximately 10X higher than any other mutation in the mammalian genome. This is especially interesting because the predicted frequency of CpG dinucleotides in the genome is 6.25% (1/16), but the actual occurrence is about 20X less. Therefore, this is showing that an epigenetic modification can lead to a genetic change. These changes are most likely to occur at CpG islands of silenced genes (because the concentration of CpG dinucleotides is higher there), but can also occur within the gene body, in non-coding regions of the genome, and in repetitive elements.
See this recent paper: S
Carina F Mugal and Hans Ellegren, 2011. ubstitution rate variation at human CpG sites correlates with non-CpG divergence, methylation level and GC content. Genome Biology, 12:R58
Thanks.
Bravo Jerry! Spot on, in every particular.
I now groan audibly when a journalist (usually from continental Europe where they spend too much time learning philosophy rather than science) asks me the now inevitable ‘what about epigenetics?’ question. It is a real disease among science journalists, this unseemly eagerness to find something that enables them to say “Darwin was wrong” (New Scientist under Roger Highfield is a lamentable example). I am heartily sick of the ‘epigenetics’ bandwagon and almost look forward to the next one, whatever it turns out to be.
Richard
When they figure out that you can even inherit money and land, that will be a revolution!
[subscribing]
/@
Not all. I am a European science journalist. Alas now unavailable on iPlayer, but I wrote and presented a Radio 4 documentary dealing with the overselling of epigenetics, broadcast in December 2010, in which we pointed out almost all of these things. In order to address the science journalist angle too, I interviewed Mark Henderson at the Times, who, I’m sure Jerry and Dawkins will agree, is pretty damn good on genetics (and is a history grad).
In my BBC4 TV documentary series “the Gene Code”, I chose not to cover epigenetics for these reasons too. It’s posted on the YouTube channel called ‘Why Evolution is True”.
Oh and here I am lambasting the Guardian for posting a specious and ridiculous feature on epigenetics. http://bit.ly/9Tf5UV
I am a science journalist. None of my colleagues fall into these traps. It is a shame to get tarred by a sloppy brush.
Scientists can fall into traps, and take science journalists with them. Some of you remember Jan Hendrik Schon, an experimental physicist at Lucent. He was on a meteoric career, having, still in his twenties, published more than a dozen papers in Nature and Science combined, and several in other prestigious physics journals. I reported on a few of his exploits, experiments that his peers could not replicate (not uncommon, look at how long it took for the creation of a Bose Einstein condensation to be replicated). I talked to dozens of them, and none of them ever questioned Schon’s results, calling him an extremely talented experimentalist (a bit shamefaced because they could not replicate the results, which, in theory were quite imaginable) . But when I was writing my last report, five minutes before deadline, I talked to a young French scientist, who squarely said that Schon is an impostor and that his papers are bogus. He sounded quite angry and arrogant, and I thought he had quite a big axe to grind, and did not quote him. A few months later Schon was found out as an impostor.
This is why Dawkins should keep reiterating his views on epigenetics to journalists, just to keep the balance straight.
man, does that sound familiar…
Marc Hauser, anyone?
I STILL think Hauser’s experimental designs are nothing short of ingenious, shortcuts in data collection and processing notwithstanding in the couple of cases where it happened.
🙁
I’d also point out, just for the record, that his larger body of work remains untouched, and nothing that has happened rejects his conclusions regarding the evolution of behavior grouped under ethics and morality.
which, I suppose, is my way of doing what you suggested Dawkins do for the epigentics issue.
…just to keep the balance straight, albeit on a different issue.
But what they really want is readership, and you don’t get readers by writing that the conventional wisdom happens to be correct.
Criminy, why must everyone tiptoe around this?
I saw people spouting the same “they’re just out for a buck” rubbish when the NYT tried to pretend the John Freshwater case was about a teacher keeping a Bible on his desk, completely eliding the utterly dull and unsensational fact that Freshwater was branding his students’ arms with an electrode.
While not as transparently crap as in that case, it’s still crap. They’re not trying to move copies with this stuff, they’re pandering to fundie zealots.
I fear this is true. My catholic sister-in-law loves epigenetics, I assume because she can use it to dis on the synthesis. She knows almost nothing about evolution but she knows she doesn’t like it!
While I appreciate the necessity to confront hype from scientists and science journalists, it is important that we not encourage people to think that their understanding of the evolutionary process is complete. For example, stress-induced nonrandom mutagenesis is of real interest in bacteriology, and it would be unfortunate if everyone reacted by dismissing it as neo-Lamarckian bullshit.
Wouldn’t that reaction boil down to a misunderstanding of what is and isn’t “Lamarckian” to begin with?
I refer to Jerry’s argument regarding imprinting above.
What drives those who overplay the epigenetics card? Is there an underlying philosophy that makes neo-Lamarkism so attractive to them?
(Note: I’ve had a lengthy exchange with an adherent of the epigenetics revolution who regarded this as propressive mainstream science but which I characterised as fringe or pseudo science. This upset him so much that he spent weeks searching my web history to find out who I am, what I do, and where I live and making veiled threats of personal harm)
you find the same kind of psychological reactions in denialism of all stripes.
it’s a defensive reaction.
of course, when you get extreme psychological defense reactions, there’s usually a reason for it (and that reason has typically little to do with whatever the denialist is actually denying!)
so, in answer to:
“Is there an underlying philosophy that makes neo-Lamarkism so attractive to them?”
no. It’s not an underlying philosophy, so much as an underlying psychology.
if you want something general to look at, try looking at why the idea of anti-materialism still remains so strong in so many people (it’s what allows the Disco Tute to keep peddling “intelligent design”, for example).
It’s like most of the planet never bothered to think past Plato.
Actually, this is something I’ve been following. For some (not all) they want it to fit their environmental agenda. They want to deny the influence of DNA in disease so that you will eat only their organic products and buy their detox products. Oh, and send money to their environmental advocacy organizations that pay their salaries.
It really is a class of DNA denialism that is brewing.
I’ve been looking for papers that have attempted to track down which parts of the genome might be involved with modifying DNA susceptibility to methylation, for example, and can’t seem to find any.
Has anyone published on this yet, Jerry?
Also:
True, but it does seem to me like there could be implications for gene frequencies in any given population.
Example:
There is a demonstrated epigenetic effect on coat color in mice (pretty much the classic case example these days, isn’t it?).
If, for example, mate choice was tied significantly to coat color in mice, that epigenetic effect might indeed have long lasting effects on the evolution of phenoytpes within a population.
It’s possible that an equilibrium would be restored after the epigenetic effects faded, but it would depend on the relative selective pressures on the traits affected, and on whether there were traits directly genetically linked to the ones epigentically affected wouldn’t it?
Well, all the parts of the genome that are CpG islands are typically conserved and hypomethylated because otherwise cytosine deamination.
I’m not sure what you’re asking but there’s epigenetic drift as a function of age for instance and running searches on methylation and tissues-specific genes might be fruitful.
There’s also more variable methylation in CpG “shores.”
Though maybe this paper is what you had in mind
Primate CpG Islands are maintained by heterogenous evolutionary regimes involving minimal selection_Cohen_2011
yup. that’s exactly the kind of thing I was looking for.
thanks muchly.
Well done! We need more scientists who will speak out on this issue.
There’s nothing about epigenetics that will change our understand of evolution. But what troubles me more is that some scientists think this is a new discovery.
DNA methylation has been known since the 1970s and the “inheritance” of methylation sites is well understood in the case of restriction/modification in bacteria. It’s been taught in molecular biology courses for over thirty years [Restriction, Modification, and Epigenetics].
It this what they mean by “recent discoveries”? I wonder why those early molecular biologists who worked with ‘phage and bacteria didn’t claim that their results would revolutionize evolution? Instead, they seemed to think that their results supported evolutionary theory.
Thank you, Dr. Coyne for this entry. I am new to biology and first heard about epigenetics last week because of the Texas Education Board/evolution issue.
I went to amazon and I saw a new book on it by Richard C. Francis, and I read reviews. I also read excerpts from other books on epigenetics on Amazon, and wondered what the fuss was all about. Frankly, there was a vaguely post-modern scent to much of the writing I saw on it.
Here is how the word came up regarding Texas school’s new text books….almost seems that the “strength and weaknesses” fans have a soft spot for epigenetics? Look specifically at #7a on top of page 2:
http://www.tfn.org/site/DocServer/HoltMcDougalEdits.pdf?docID=2741
Dr., Dr., send me the news:
What’s up with blind cave-dwelling fish, which when moved to a lighted environment develop eyes that persist over subsequent generations?
If you don’t know what I’m talking about, I’ll get off my lazy ass and look it up.
1st guess:
the absence of light is used as a developmental trigger NOT to continue the pathway to form eyes.
restore light during specific developmental stages, and you re-trigger the developmental pathway to proceed.
I haven’t a clue what species you’re referring to though; it sure ain’t a universal trait of how eyelessness has evolved in fishes.
No, no. Eye development was induced in the lab by implanting lens tissue from another (closely related but sighted) fish, not by simply changing the environment.
Jerry,
Would you consider submitting a version of that to the Guardian? I’d love to read it over breakfast with my (paper) copy.
Evolution is rather a creative process than accumulation of random mistakes! Eshel Ben-Jacob:
http://bit.ly/rn1N0C
“I am not aware of a single case in which an adaptive change in an organism—or any change that has been fixed in a species—rests on inheritance that is not based on changes in the DNA.”
I can give you that:
http://www.nature.com/nature/journal/v401/n6749/full/401157a0.html
Cubas, P., Vincent, C. & Coen, E., 1999. An epigenetic mutation responsible for natural variation in floral symmetry. Nature, 401(6749), pp.157-161.
Honestly, I wonder how you can miss that, as your link directly before the quoted sentence mentions toadflax. Maybe you did not understand the paper?
It says the toadflax mutant with peloric flowers, which propagated stably for at least 250 years in the environment (Linnaeus described it first), has a mutated flower-asymmetry gene which differs to the wild type gene sequence only in one base in the 3′ untranslated region but is hypermethylated. The hypermethylated allele (epiallele = differs only in heritable epigenetic modification pattern) is transmitted stably in the germ line and recessive to the wild type epiallele. Because of the presumed stable inheritance for 250 years, the epiallele is presumably adaptive. It can occasionally revert to a hypomethylated state, and this is how it can be shown that the epigenetic state of the allele is the cause of the peloric flower, as toadflax which are epigenetic mosaics for the methylated state of the LCYC gene have more wildtypic flowers on their hypomethylated stems. The reversion is also evidence that the hypermethylated epiallele is adaptive, as the spontaneously occurring wildtypes would outcompete the epimutants in the environment if it was not.
“I am not aware of a single case in which an adaptive change in an organism—or any change that has been fixed in a species—rests on inheritance that is not based on changes in the DNA.”
I can give you that:
Cubas, P., Vincent, C. & Coen, E., 1999. An epigenetic mutation responsible for natural variation in floral symmetry. Nature, 401(6749), pp.157-161.
Honestly, I wonder how you can miss that, as your link directly before the quoted sentence mentions toadflax. Maybe you did not understand the paper?
It says the toadflax mutant with peloric flowers, which propagated stably for at least 250 years in the environment (Linnaeus described it first), has a mutated flower-asymmetry gene which differs to the wild type gene sequence only in one base in the 3′ untranslated region but is hypermethylated. The hypermethylated allele (epiallele = differs only in heritable epigenetic modification pattern) is transmitted stably in the germ line and recessive to the wild type epiallele. Because of the presumed stable inheritance for 250 years, the epiallele is presumably adaptive. It can occasionally revert to a hypomethylated state, and this is how it can be shown that the epigenetic state of the allele is the cause of the peloric flower, as toadflax which are epigenetic mosaics for the methylated state of the LCYC gene have more wildtypic flowers on their hypomethylated stems. The reversion is also evidence that the hypermethylated epiallele is adaptive, as the spontaneously occurring wildtypes would outcompete the epimutants in the environment if it was not.
Mo,
I think there’s a lot of potential for adaptive epigenetic inheritance in nature, but I don’t regard Cubas et al. 1999 as particularly good evidence in favor of it. First, I don’t think it’s clear that the hypermethylated state of Lcyc has been stably inherited since the time of Linnaeus. Cubas et al. show inheritance of the hypermethylated state for only two generations (if I remember correctly), with some reversions, as you note. Second, I’m a stickler on the definition of adaptation, and it’s not clear to me that the peloric form is adaptive (though I’m not very familiar with Linaria vulgaris). Do you know of any data that show higher maternal fecundity, offspring survival (or better yet, the product of both) for peloric flowers compared to wild type?
And to suggest that Jerry didn’t understand the paper? Come on.
This issue reminds me of something in Richard Lewontin’s “Billions and Billions of Demons”, his review of Carl Sagan’s “The Demon-Haunted World”: http://www.drjbloom.com/Public%20files/Lewontin_Review.htm
He claimed: Repeatable observations that do not fit into an existing frame have a way of disappearing from view, and the experiments that produced them are not revisited. In the 1930s well-established and respectable geneticists described “dauer-modifications,” environmentally induced changes in organisms that were passed on to offspring and only slowly disappeared in succeeding generations. As the science of genetics hardened, with its definitive rejection of any possibility of the inheritance of acquired characteristics, observations of dauer-modifications were sent to the scrapheap where they still lie, jumbled together with other decommissioned facts.
Is there *any* truth in that?
The rest of Dr. Lewontin’s review is rather crude science-bashing, like calling creationism some sort of proletarian revolt against an evolution-believing bourgeoisie, and saying how absurd the theories of modern science are. Does he agree with Lactantius that the Earth must be flat because everything on the antipodes would fall upward?
I have read Darwin – and I recommend him to evolutionary biologists (and even neo-Darwinians) who have not bothered to do so. He was a good writer, and very accessible.
Darwin would be delighted with all of this. He assumed that only some of his lesser hypotheses would turn out to be correct, and sure enough, his ideas about some details of evolution were wrong. He knew that better data would bring better understanding of the underlying mechanisms.
A lot of of Darwin’s observations and speculations about the mechanics of inheritance, though, fit very nicely with a combination of modern genetics and our unfolding understanding of epigenetics. He was more right than geneticists used to believe he was, which I think he would find gratifying.
I think that J A Coyne is down to the point in his paper : ” Is epigenetics…? ”
It’s typical for some scientists, an formany non-scientists who are interested in the disiplins of natural science to proclame (now and then)that we now are at the turning point in the history of ideas.
This hope for a new revolution in science is especially found and proclamed in teh New Age-movement over the years. And they have a reference to T S Kuhns famous notions ‘ paradigma’ and ‘ a shift of paradigms’ seen as a ‘ revolution’ in science ( T S Kuhn: “The structure of scientiffic revolution”.
But,- very often these notions are misinterpreted and used in a ‘ non-Kuhnian’ way.
The latest findings in the study of epigenetics I think are in themselves ‘wonderfull’ enought on their own way. They don’t need to be ‘revolutionary’ in order to be of great interest within the study of genetics although the epigenetic field of study is just opening up for a broader perspective w i t h i n the stablished neo-darwinean paradigma.
From my point of view, the science of evolutionary epigenetics opens up for a further research w i t h i n a ‘ biosemiotic’ perspective on the genetic level. ( Se Jesper Hoffmeyer, Claus Emmeche and Thomas Sebeok).
Within t h i s perspective there is an ongoing interconnected exchange of biosemiotic-signs between genes and epigenes and also within the organism and environment:
‘ A sign is a d i f f e r e n s that makes a difference’, Gregory Bateson says. That is to say that mind is seen as a kind of an interpreter operating within the cells. The american pragmatist Carles Sanders Pierce has even a more explicit definition when he says that a sign is ‘something’ that f o r ‘someone’ stands for ‘something’ (in respekt to a context).This view is a triggering one.
By the way: The lamarckian hypothesis of inheritance, I think, was not totally excluded as a ‘hypotheses’ in evolution by Darwin himself although his main and general theories of the mecanisms of evolution later on were seen as the opposite of the lamackian view of evolution in biology.
Isn’t it – afterall – wonderfull to see how modern biology, evolutionary science and epigenetics still, step by step open up our e y e s for a broader and more complex study of life: The study of signs of l i f e and the life og s i g n s.
Carl Christian Andersen, Norway
I fail to see how this couldn’t be accounted for through natural selection and genetic drift.
Dear Jerry,
It’s fair enough if you dismantle a book’s argument after reading it but it’s more than a little disingenuous to dismantle it only through reading a review in a broadsheet paper. After all, you wouldn’t want people to think you were dogmantic and entrenched in your views would you?
For the record, the book itself contains a lot of journal references from 2010 and 2011. That doesn’t make it any more right but it does make it less of a tired trotting out of what we’ve heard before (although, to be fair, it does contain the mice but then there’s a history to the story… ditto the ubiquitous Paley in books about evolution). And it doesn’t, for one moment, suggest evolution isn’t true… quite the opposite. of course, if you’d read the book, you’d know that.
Finally, perhaps the pubilsher played a role in the book’s title.
Seriously though, I think I’d trust (important word trust) your judgement more if you were criticising the book itself.
Yours,
Simon
I agree. I’m 40% through the book and so far it makes no claims regarding the role epigenetics plays on the evolution of species.
I would like to by my girlfriend a book on epigenetics for christmas as she is interested in the subject, can you recommend a good book that I could buy
Many thanks
Paul
The Epigenetics Revolution : How Modern Biology Is Rewriting Our Understanding of Genetics, Disease and Inheritance
Carey, Nessa
ISBN 10: 1848313470 / 1-84831-347-0
ISBN 13: 9781848313477
thank you very much. I have researched many books after reading all the above & was finding it difficult after reading so many mixed reviews. I will happily go with your recommendation 🙂