Razib Khan One-stop-shopping for all of my content

June 20, 2011

Breaking the “Central Dogma”

Epigenetics is making it “big time,” Slate has a review up of the new book Epigenetics: The Ultimate Mystery of Inheritance. In case you don’t know epigenetics in terms of “what it means/why it matters” holds out the promise to break out of the genes → trait conveyor belt. Instead positing genes → trait → experience → genes, and so forth. Or perhaps more accurately  genes → trait × experience → genes. Epigenetics has obviously long been overlooked as a biological phenomenon. But, I think the same could be said for the ubiquity of asexual reproduction and unicellularity! Life science exhibits anthropocentrism. That’s why there’s human genetics, and biological anthropology. My own concern is that epigenetics will give some a license to posit that the old models have been overthrown, when in fact in many cases they have been modified on the margin. Especially at the level of organisms which we’re concerned about; human-scaled eukaryotes. Humans most of all.

The last paragraph in the review highlights the hope, promise, and perils of epigenetics in regards to social relevance:

It’s almost enough to make one nostalgic for the simplicity of old-style genetic determinism, which at least offered the sense that the ...

October 7, 2010

Epigenetics – what revolution?

Filed under: Epigenetics,Genetics,Genomics — Razib Khan @ 12:06 am

A reader who goes by the handle “biologist,” and happens to be a molecular geneticist by training, states more clearly what is probably close to my own position (though he is far more well informed) in the comments below. I think it’s worth promoting:

As far as I can tell, the existence of epigenetic mechanisms doesn’t change anything that we *should* have already known about the social implications of genetics (i.e. what people care about).

Quantitative genetic methods that estimate a substantial contribution of genetic variation to phenotypic variation do not now and has never told us anything about actual or counterfactual causal mechanisms involved. They have also never told us much about development other than what we already knew must be true — there will be genes involved in some way.

Nothing we’ve learned in the last 30 years about molecular biology makes any difference at a general level to those conclusions. What it mostly does is make clearer that the causal mechanisms behind phenotypic variation in complex traits are probably themselves really really complex.

As soon as you realize that complex traits have non-Mendelian inheritance patterns — something that’s been abundantly clear for many many decades — everything else follows and epigenetics only adds new dimensions to the causal mechanisms that might be involved.

Whether a trait is amenable to manipulation (and at what stages of development) is an interesting and very challenging question, but there’s no revolution in our understanding of biology involved in asking it. The only way to see a revolution is to ignore all of the incremental changes in understanding that have happened between decades.

Just to be clear, this is not a very mature sounding 12 year old. The commenter above is a biologist with whom I am personally familiar and whose opinion on this topic I value because not only do they grasp molecular biology in its fine-grained details, but they are very familiar with quantitative and behavior genetics (a rare combination). I can probably transfer some of the same general cautions about epigenetics that I brought up with Jim Manzi in relation to epistasis several years back.

The great thing about science is that this likely won’t be a debate 10-20 years from now. If you have an equation of the form:

A[genetics] + B[epigenetics] + C[environment] → Outcome

The scalars A, B, and C will be known with more precision as science progresses. Or more accurately, their values will be known for the range of outcomes which we find of interest. Our current surfeit of commentary is a function of mystery and uncertainty.

October 6, 2010

Arise the vehicle! Arise the cell!

Filed under: Epigenetics,Genetics,Genomics — Razib Khan @ 2:00 pm

A quick follow up to my post Epigenetics arise! Adam Keiper, the editor of The New Atlantis, has graciously sent me a copy of the article, Getting Over the Code Delusion. I’ve also been told that the piece will be free to all on the website at any moment, so I invite readers to check it out when that occurs [it's online].

First, I want to add that Mr. Keiper doesn’t believe that the Wikipedia entry for The New Atlantis is particularly accurate. William Kristol for example has never been published in The New Atlantis, while the Wikipedia entry says he has. I would add though that many of the people associated with the magazine may broadly be considered “conservative.” Not that there’s anything wrong with that, I too may broadly be considered “conservative”! Others associated with the publication, such as Robert Zubrin, are not known for their politics from what I know.

As for Steve Talbott’s essay, it’s a peculiar beast. It weighs in at 25 pages, but it’s only the first of a series. Getting Over the Code Delusion is to a large extent a primer on molecular genetics, cytology, and genomics for the uninitiated. That’s a tall order. It’s really hard to avoid pitfalls of oversimplification in the space provided, so I’ll let readers judge where Talbott misleads or misunderstands in the details. Another definite aspect of the piece which is a bit out of the ordinary is its literary quality, which one does not usually find in primers of this sort. Consider:

…Noncoding DNA could provide the complex regulatory functions that direct genes toward service of the organism’s needs, including its developmental needs.

That suspicion has now become standard doctrine….

I think coventional technical writing would have avoided a word like “doctrine” (and I think it also misleads as to the disputes around issues such as the importance of cis-regulatory elements, which are not quite settled). But Talbott’s audience does not necessarily consist of individuals who get Science and Nature in the mail every month (or have academic access). So a more thorough judgement probably will have to await the whole series.

But I think I can already glean the gist of where Talbott is going: he wants to dethrone the centrality of the genetic sequence in our understanding of how life emerges and is specified. He is right to point out that debates about the importance of gene regulation, higher order genomic structures, and epigenetics, throw a monkey-wrench into a cool reductionist system where the mapping between genotype and phenotype is going to be easy to unravel. In this Steve Talbott is following many others who have objected to the image of genes as “puppet masters” which control our destinies. Included in this set is Richard Dawkins, who felt that the publicity materials around The Selfish Gene, and misunderstandings by other academics, resulted in a distortion of his underlying message. But in any case the science is still very much in flux. The old order may have fallen, but nothing has risen to replace it. Talbott nicely reminds us that 20 years ago mainstream scientists were engaging in genetic triumphalism with the success of family based linkage studies in adducing variants associated with recessive diseases such as cystic fibrosis. But my main worry is that the triumphalists of our age are again speaking too soon. Science is always full of surprises.

Addendum: One impression I get from Getting Over the Code Delusion is that the author is eliding the distinction between deterministic processes understood on a molecular genetic scale, and statistical associations on the scale of populations and the level of genomics. Prediction need not be conditional on perfection, and clearly systematic patterns and processes can emerge from a seemingly chaotic welter. That’s what developmental genetics certainly teaches. Also, early in the piece Talbot seems to be diminishing the importance of the sequence identity between the chimpanzee and the human, asking that “…we could have done the obvious and direct and scientifically respectable thing: we could have observed ourselves and chimps, noting the similarities and differences.” I think this sort of common sense objective phenetics when it comes to humankind’s closest relatives is not so easy to come by. A history of the taxonomic and evolutionary confusions as to the nature of relations among the homonid lineage are such that this was one area where phylogenetics informed at the sequence level was very useful. Perhaps it’s been overplayed, but it was, and is, a very significant finding, and the perceptions of broad phenotypic differences don’t refute that reality.

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