Tag: epigenesis

More on Mukherjee

May 21, 2016 • 12:00 pm

We’ll have two guest posts today, and the second comes from Greg Mayer, who’s been AWOL for a while (he’s now in Costa Rica).

by Greg Mayer

As WEIT readers know, Pulitzer Prize winning author and physician Siddharta Mukherjee has been in the news since he published an article in the New Yorker on “epigenetics”. Surprisingly for such an accomplished author, he presented a rather misleading view of the field of gene regulation, emphasizing what he called “epigenetics”. This has led to widespread criticism by the leading lights of molecular biology, and Jerry has provided rather full discussion of theses criticisms, including posting statements from a number of prominent molecular biologists (here, here, here, and here). Among those sharing thoughts and criticisms with Jerry were Mark Ptashne and Wally Gilbert. Such great molecular biologists may not be household names, so to put this in terms WEIT readers will readily comprehend, this is like having Darwin and Wallace criticize your article about evolution.

The article was sort of a teaser for Mukherjee’s new book, The Gene, and Jerry noted the New York Times‘ review of it in its weekday book review. Now, two more reviews have appeared this week in the Times, in the Sunday Book Review, and in the Tuesday Science section. Both are laudatory, the former including words such as “clarifying” and “definitive”. I was particularly struck by that reviewer’s statement that Mukherjee views his subject “panoptically”, which contrasts strongly with what Matthew wrote in his mixed review of the book for Nature:

Furthermore, because the book centres on medical genetics, anyone expecting an exploration of the state of genetics as a whole will be disappointed. Our Genes would have been a more appropriate title than The Gene.

While not quite myopic, this is far from panoptic. The reviewer does, however, mention Dawkins’ analogy of the DNA sequence as a “recipe”, which of course is much more apt than the common but misleading analogy of DNA as a “blueprint”.

Mukherjee’s book promotion continues apace: he has another Times piece about him forthcoming, and last Sunday I heard on the radio parts of an interview with him on “The New Yorker Radio Hour”. Based on what I heard, he really seems confused about the meaning of the word epigenetics. He seems to want it to mean any non-genetic (sensu-stricto) influence on development, but this usage is in fact close to C.H. Waddington’s (i.e., the traditional) definition of  “epigenetics” which I prefer. Mukherjee has mixed up that correct usage (after all, development is epigenetic) with the new usage of the word by certain molecular biologists to mean anything weird: “all the weird and wonderful things that can’t be explained by genetics”, and so he mistakes the deeply important fact that development is epigenetic (in the traditional sense), with the importance of the molecular oddity du jour.

On a personal note, I was heartened to learn from the comments by leading molecular biologists that they too are unhappy with the appropriation and overuse of the word “epigenetics”.  When I mentioned my unhappiness at this in an earlier post, a number of commenters thought it was too late to go back to the meaning based on epigenesis: “epigenetics” now firmly applied to the weird things, they wrote. So I’m glad to see that that’s not the case, at least among some of the leading molecular biologists. To understand the history of the word, the best place to go is still David Haig’s paper on the subject.

[JAC: I’ll have a few more words about The Atlantic‘s review of Mukherjee’s book tomorrow.]

Haig, D. 2004. The (dual) origin of epigenetics. Cold Spring Harbor Symposia on Quantitative Biology 69:1-4.

Development is epigenetic

May 14, 2011 • 10:21 am

by Greg Mayer

One of the points I stress to students in my evolution class is that development is epigenetic: organisms develop from a less differentiated state to a more differentiated state. In modern terms, genes, the intraembryonic environment, and the extraembryonic environment interact to produce the organism through a sequence of stages going from an undeveloped to a mature state. The general point (though not the part about genes) has been known for a couple of centuries, so it might seem it wouldn’t be necessary to emphasize it, but the alternative view of development– preformationism— has a surprising hold on people’s minds. Preformationism maintains that development is essentially growth: there is in the germ cells a differentiated organism, which grows or unfolds during the course of development.

A homunculus inside a sperm, by Nicolaas Hartsoeker, 1695. This is not how development works.

Preformationism, though wrong, is frequently reinforced by the common (though badly mistaken) practice of referring to DNA or the genome as a “blueprint” for the organism. It is of course no such thing. A blueprint is a two dimensional representation of a three dimensional object. There is, in a blueprint, a scaled representation of all the parts of the object. We can tell, for example, that the window on the second floor is 4 m above and 2m to the left of the door. There is nothing like that in your DNA: there isn’t a gene for your left eye, which is a scaled distance away from the gene for your right eye. Your DNA (and your development) is much more akin to a recipe. In a raisin cake recipe, there isn’t a line in the recipe that says place a raisin 2 cm in from the upper left hand corner (there would be, if we had a blueprint for the cake). Rather, if you combine the right ingredients, in the right sequence, in the right environment, the result is a cake with raisins distributed through it at a certain density.

Richard Dawkins expounds the recipe analogy in The Blind Watchmaker (1986, pp. 295-296):

A recipe in a cookery book is not, in any sense, a blueprint for the cake that will finally emerge from the oven…. a recipe is not a scale model, not a description of a finished cake, not in any sense a point-for-point representation. It is a set of instructions which, if obeyed in the right order, will result in a cake.

Now, we don’t yet understand everything, or even most things, about how animals develop from fertilized eggs. Nevertheless, the indications are very strong that the genes are much more like a recipe than like a blueprint. Indeed, the recipe analogy is really rather a good one, while the blueprint analogy, although it is often unthinkingly used in elementary textbooks, especially recent ones, is wrong in almost every particular. Embryonic development is a process. It is an orderly sequence of events, like the procedure for making a cake…

The genes, taken together, can be seen as a set of instructions for carrying out a process, just as the words of a recipe, taken together, are a set of instructions for carrying out a process.

The reason this is important for students of evolution is that most of evolution is the modification of pre-existing structures, and these structures arise in the organism via a process of epigenetic development. Thus, most of evolution is the modification of pre-existing developmental programs.  Evolution doesn’t swap out one adult structure for another, but rather alters developmental programs, which results in differences in adults.  To understand phenotypic evolution, we must understand the variations which alterations of the developmental program can give rise to, their natures, and frequency. These studies are the domain of what has come to be called “evo-devo“. (From the evidence of at least vertebrate paleontology [this, this, and this], we can expand the generalization and say that most of evolution is the gradual, adaptive, modification of pre-existing developmental programs.)

I’ll finish this post with three brief observations. First, doesn’t it seem strange that the man who has provided the most compelling way of seeing the complex and interactive nature of development has been so frequently assailed for being reductionist and atomistic? Second, the fact that certain genes that have a major effect on development (Hox genes) are arranged along chromosomes in antero-posterior order of their influence on the developing body, while not preformationist, is nonetheless an intriguing and unexpected correspondence of the spatial arrangement of the body and the genes. And third, I’m using epigenetic in the original embryological/morphological sense, from which C.H. Waddington derived the term “epigenetics” in 1942, and not the recent odd usage, in which epigenetic means ‘heritable variation not associated with nucleic acid variation’ or, even more oddly, “all the weird and wonderful things that can’t be explained by genetics“; the hijacking of the word, and the conflation of the pseudo-neologism with Waddington’s ideas, have been nicely explicated in a paper by David Haig. Epigenesis is too useful a concept to lose the word for it.

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Dawkins, R. 1986. The Blind Watchmaker. W.W. Norton, N.Y.

Haig, D. 2004. The (dual) origin of epigenetics. Cold Spring Harbor Symposia on Quantitative Biology 69:1-4.