Any sufficiently convoluted explanation for biological phenomena is indistinguishable from epigenetics.<\/em><\/strong><\/p>\n

$\"Epigenetics\"$ <\/a>
Use of the word “epigenetics” over time<\/strong><\/center><\/p><\/div>\n
Epigenetics is everywhere.\u00a0Nary a day goes by without some\u00a0news story or press release telling us something it\u00a0explains.<\/p>\n
Why does autism run in families? \u00a0Epigenetics.
\nWhy do you have trouble\u00a0losing weight? Epigenetics.
\nWhy are\u00a0vaccines dangerous? Epigenetics.
\nWhy is cancer so hard to fight? Epigenetics.
\nWhy a cure for cancer is around the corner? Epigenetics.
\nWhy your parenting choices might affect your great-grandchildren? Epigenetics.<\/p>\n
Epigenetics\u00a0is used as shorthand in the popular press for any of a loosely connected set of phenomenon purported to result in experience being\u00a0imprinted in DNA and transmitted across time and\u00a0generations.\u00a0Its\u00a0place in our lexicon has grown\u00a0as\u00a0biochemical discoveries have given ideas of extra-genetic inheritance\u00a0an air of molecular plausibility.<\/p>\n
Biologists now invoke epigenetics to explain all manner of observations that lie outside their current ken. Epigenetics pops up frequently among non-scientists in all manner of discussions about heredity. And\u00a0all manner of crackpots slap “epigenetics” on their fringy ideas to give them a veneer of credibility.\u00a0But epigenetics\u00a0has achieved buzzword status far faster and to a far larger extent\u00a0than current\u00a0science justifies, earning\u00a0the disdain of scientists (like me) who study how information is encoded, transferred and read out across cellular and organismal generations.<\/p>\n
This simmering conflict came to a head last week around an article in The New Yorker, <\/em>“Same but Different<\/a>”\u00a0by\u00a0Siddhartha Mukherjee that juxtaposed a meditation on the differences between his mother and her identical twin with a discussion of the research of Rockefeller University’s David Allis on the biochemistry of DNA and the proteins that encapsulate it in cells, that\u00a0he and others believe provides a second mechanism for the encoding and transmission of genetic information.<\/p>\n
Although Mukherjee hedges throughout his piece, the clear implication of the story is that Allis’s work provides an explanation for differences that arise between genetically identical individuals, and even suggests that they open the door to legitimizing the long-discredited ideas of the 19th century naturalist\u00a0Jean-Baptiste Lamarck who thought that organisms could pass beneficial traits acquired during their lifetimes on to their offspring.<\/p>\n
The piece earned a sharp rebuke from many scientists<\/a>, most notably\u00a0Mark Ptashne who has long led the anti-epigenetics camp, and John Greally, who published a lengthy take-down of Mukherjee’s piece<\/a>\u00a0on the blog of evolutionary biologist Jerry Coyne.<\/p>\n
The dispute centers on the process of gene regulation, wherein the\u00a0levels of specific\u00a0sets of genes are tuned\u00a0to confer distinct\u00a0properties on\u00a0different sets of cells and tissues during development, and in response to internal and external stimuli. Gene regulation is central to the encoding of organismal form and function in DNA, as it allows different cells and even different individuals of a species to have identical DNA and yet manifest different phenotypes.<\/p>\n
Ptashne has studied the molecular basis for gene regulation for fifty years. His and Greally’s critique of Mukherjee, or really Allis, is rather\u00a0technical, and one could quibble about some of the specifics.\u00a0But his main points are simple and difficult to refute:<\/p>\n
\n
There is essentially no evidence to support the idea that chemical modification of DNA and\/or its accompanying proteins is used to encode and\u00a0transmit\u00a0information over long periods of time.<\/li>\n
<\/p>\n
Rather than representing a separate system for storing and\u00a0conveying\u00a0information, a wide range of experiments\u00a0suggests that the primary role of the biochemistry in question is to execute gene expression programs encoded in DNA and read out by a diverse set of proteins known as transcription factors that bind to\u00a0specific sequences in DNA and regulate the expression of nearby genes.<\/li>\n<\/ul>\n
In one way this debate is\u00a0incredibly important because it is ultimately about getting the science right. Mukherjee’s piece contained several inaccurate statements and, by focusing on one aspect of Allis’s work, gave an woefully\u00a0incomplete picture of our current understanding of gene regulation.<\/p>\n
Any system for conveying information about the genome – which is what Mukherjee is writing about –\u00a0has to\u00a0have some way to\u00a0achieve genomic specificity so that the expression of genes can be tuned up or down in a non-random manner.\u00a0Transcription factors, which bind on to specific DNA sequences,\u00a0provide a\u00a0link between the specific sequence of DNA\u00a0and the cellular machines responsible for turning information in DNA into proteins and other biomolecules. Small RNAs, which can bind to complementary sequences in DNA, also have this capacity.<\/p>\n
But there is scant\u00a0evidence for sequence specificity in the activities of the\u00a0proteins that modify DNA and the nucleosomes around which it is wrapped. Rather they get their specificity from transcription factors and small RNAs. That doesn’t render this\u00a0biochemistry\u00a0unimportant – the broad conservation of proteins involved in modifying histones shows they play important roles – but ascribing regulatory primacy to DNA methylation and histone modifications is not consistent with our current understanding of gene regulation.<\/p>\n
Something is, however, getting lost in\u00a0this back-and-forth , as one might come away with the impression that this is disagreement\u00a0about whether\u00a0cells and organisms can transmit information\u00a0in a manner above and beyond DNA\u00a0sequence. And this is unfortunate, because there really is no question about this. Ptashne and Allis\/Mukherjee are\u00a0arguing about the molecular details of how it\u00a0happens and about how important different\u00a0phenomena are.<\/p>\n
Various forms of non-Mendelian information transfer are well established. The most important of which happens in every animal generation, as eggs contain not only DNA from the mother, but also a wide range of proteins, RNAs and small molecules that drive the earliest stages of embryonic development. The particular cocktail left by the mother can have profound effects on the new organism – so called “maternal effects”. These effects can be the result of both the mothers genotype, the environment in which she lives, and, in various ways, her experiences during her life. (Such phenomena are not limited to multicellular critters – single-celled organisms\u00a0distribute many molecules asymmetrically when they divide, conferring different phenotypes to their different genetically identical offspring).<\/p>\n
Many maternal effects have been studied in great detail, and in most cases the transmission of state involves the transmission of\u00a0different concentrations and activities of proteins (including transcription factors) and RNAs. That is the transmitted DNA is identical, but the state of the machinery that reads out the DNA is different, resulting in different outcomes.<\/p>\n
However there are some good examples in which modifications to DNA play an important role in the transmission of information across generations – most notably with “imprinting”, in which an organism preferentially utilizes the copy of a gene it got from one of its parents independent to the exclusion of the other in a way that appears to be independent of the sequence of the gene. Imprinting, which is a relatively rare, but sometimes important, phenomenon appears to arise from parent-specific methylation of DNA.<\/p>\n
Could the histone modifications that Allis studies and Mukherjee focuses on also carry information across cell divisions and generations?\u00a0Sure. Our understanding of gene regulation is still fairly primitive, and there\u00a0is plenty of room for the discovery of important\u00a0inheritance mechanisms involving histone modification. We have to keep an open mind. But the point the critics of Mukherjee are really making is that given what is known today about mechanisms of gene regulation, it is\u00a0bizarre bordering on irresponsible to focus on a mechanism of inheritance that only might<\/strong><\/span> be real.<\/p>\n
And\u00a0Mukherjee is far from the only one to have fallen into this trap. Which brings me to what I think is the most interesting question here: why does this particular type of epigenetic inheritance involving an obscure biochemical process have such strong appeal? I think there are several things going on.<\/p>\n
First, the\u00a0idea of a “histone code” that supersedes the information in DNA exists (at least for now) in a kind of limbo: enough biochemical specificity to give it credibility\u00a0and a ubiquity that makes is seem important, but sufficient mystery about what it actually is and how it might work\u00a0that people can imbue it with whatever properties they want. And\u00a0scientists and non-scientists alike\u00a0have leapt into this molecular biological sweet spot,\u00a0using this manifestation\u00a0of the idea of epigenetics as a generic\u00a0explanation for\u00a0things they can’t understand, a\u00a0reason to hope that things they want to be true might really be, and as a difficult to refute, almost quasi-religious, argument for the plausibility of almost any idea linked to heredity.<\/p>\n
But there is also\u00a0something more specifically appealing about this particular idea. I think it stems from the fact that epigenetics in general, and the idea of a “histone code” in particular, provide a strong counterforce to the rampant genetic determinism that has dominated the genomic age. People don’t like to think that everything about the way they are and will be is determined by their DNA, and the idea that\u00a0there is some magic wrapper around DNA that can be shaped by experience to override what is written in the primary code is quite alluring.<\/p>\n
Of course DNA is not destiny, and we don’t need to evoke etchings on DNA to get out of it. But I have a feeling it will take more than a few arch retorts from transcription factor extremists to erase epigenetics from the zeitgeist.<\/p>\n","protected":false},"excerpt":{"rendered":"
Any sufficiently convoluted explanation for biological phenomena is indistinguishable from epigenetics. Epigenetics is everywhere.\u00a0Nary a day goes by without some\u00a0news story or press release telling us something it\u00a0explains. Why does autism run in families? \u00a0Epigenetics. Why do you have trouble\u00a0losing weight? Epigenetics. Why are\u00a0vaccines dangerous? Epigenetics. Why is cancer so hard to fight? Epigenetics. Why […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[93,15,21,79],"tags":[],"_links":{"self":[{"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/1894"}],"collection":[{"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1894"}],"version-history":[{"count":18,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/1894\/revisions"}],"predecessor-version":[{"id":1913,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/1894\/revisions\/1913"}],"wp:attachment":[{"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1894"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1894"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.michaeleisen.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1894"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}